Leuprolide acetate is a synthetic nonapeptide analog of naturally occurring gonadotropin releasing hormone (GnRH or LH-RH). 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:

LUPRON INJECTION is a sterile, aqueous solution intended for subcutaneous injection. It is available in a 2.8 mL multiple-dose vial containing leuprolide acetate (5 mg/mL), sodium chloride, USP (6.3 mg/mL) for tonicity adjustment, benzyl alcohol, NF as a preservative (9 mg/mL), and water for injection, USP. The pH may have been adjusted with sodium hydroxide, NF and/or acetic acid, NF.

LUPRON INJECTION (leuprolide acetate) is indicated in the palliative treatment of advanced prostatic cancer.

The recommended dose is 1 mg (0.2 mL or 20 unit mark) administered as a single daily subcutaneous injection. As with other drugs administered chronically by subcutaneous injection, the injection site should be varied periodically. Each 0.2 mL contains 1 mg of leuprolide acetate, sodium chloride for tonicity adjustment, 1.8 mg of benzyl alcohol as preservative and water for injection. The pH may have been adjusted with sodium hydroxide and/or acetic acid.

Follow the pictorial directions on the reverse side of this package insert for administration.

NOTE: As with all parenteral products, inspect the solution for discoloration and particulate matter before each use.

LUPRON INJECTION (leuprolide acetate) is a sterile solution supplied in a 2.8 mL multiple-dose vial. The vial is packaged as follows: 14 Day Patient Administration Kit with 14 disposable syringes and 28 alcohol swabs, NDC 0300-3612-28 and six-vial carton, NDC 0300-3612-24.

Store below 77°F (25°C). Do not freeze. Protect from light; store vial in carton until use.

CLINICAL TRIALS

In the majority of patients testosterone levels increased above baseline during the first week, declining thereafter to baseline levels or below by the end of the second week of treatment. This transient increase was occasionally associated with a temporary worsening of signs and symptoms, usually manifested by an increase in bone pain (see WARNINGS section). In a few cases a temporary worsening of existing hematuria and urinary tract obstruction occurred during the first week. Temporary weakness and paresthesia of the lower limbs have been reported in a few cases.

Potential exacerbations of signs and symptoms during the first few weeks of treatment is a concern in patients with vertebral metastases and/or urinary obstruction which, if aggravated, may lead to neurological problems or increase the obstruction.

In a comparative trial of LUPRON INJECTION (leuprolide acetate) versus DES, in 5% or more of the patients receiving either drug, the following adverse reactions were reported to have a possible or probable relationship to drug as ascribed by the treating physician. Often, causality is difficult to assess in patients with metastatic prostate cancer. Reactions considered not drug related are excluded.

In this same study, the following adverse reactions were reported in less than 5% of the patients on LUPRON. Cardiovascular System¾ Angina, Cardiac arrhythmias, Myocardial infarction, Pulmonary emboli; Gastrointestinal System¾ Diarrhea, Dysphagia, Gastrointestinal bleeding, Gastrointestinal disturbance, Peptic ulcer, Rectal polyps; Endocrine System¾ Libido decrease, Thyroid enlargement; Musculoskeletal System¾ Joint pain; Central/Peripheral Nervous System¾ Anxiety, Blurred vision, Lethargy, Memory disorder, Mood swings, Nervousness, Numbness, Paresthesia, Peripheral neuropathy, Syncope/ blackouts, Taste disorders; Respiratory System¾ Cough, Pleural rub, Pneumonia, Pulmonary fibrosis; Integumentary System¾ Carcinoma of skin/ear, Dry skin, Ecchymosis, Hair loss, Itching, Local skin reactions, Pigmentation, Skin lesions; Urogenital System¾ Bladder spasms, Dysuria, Incontinence, Testicular pain, Urinary obstruction; Miscellaneous¾ Depression, Diabetes, Fatigue, Fever/chills, Hypoglycemia, Increased BUN, Increased calcium, Increased creatinine, Infection/inflammation, Ophthalmologic disorders, Swelling (temporal bone).

In an additional clinical trial and from long-term observation of both studies, the following additional adverse events (excluding those considered not drug related) were reported for patients receiving LUPRON.

Cardiovascular System¾ Bradycardia, Carotid bruit, Extrasystole, Palpitations, Perivascular cuffing (eyes), Ruptured aortic aneurysm, Stroke, Tachycardia, Transient ischemic attack; Gastrointestinal System¾Flatus, Dryness of mouth and throat, Hepatitis, Hepatomegaly, Occult blood (rectal exam), Rectal fistula/erythema; Endocrine System¾Libido increase, Thyroid nodule; Musculoskeletal System¾Ankylosing spondylosis, Arthritis, Blurred disc margins, Bone fracture, Muscle stiffness, Muscle tenderness, Pelvic fibrosis, Spasms/cramps; Central/Peripheral Nervous System¾Auditory hallucinations/tinnitus, Decreased hearing, Decreased reflexes, Euphoria, Hyperreflexia, Loss of smell, Motor deficiency; Respiratory System¾Chest tightness, Decreased breathing sounds, Hemoptysis, Pleuritic chest pain, Pulmonary infiltrate, Rales/rhonchi, Rhinitis, Strep throat, Wheezing/bronchitis; Integumentary System¾Boil (pubic), Bruises, Hives, Keratosis, Mole, Shingles, Spiders; Urogenital System¾ Blisters on penis, Inguinal hernia, Penile swelling, Post void residual, Prostatic pain, Pyuria; Miscellaneous¾Abdominal distention, Facial swelling/edema, Feet burning, Flu, Eyelid growth,Hypoproteinemia, Accidental injury, Knee effusion, Mass, Pallid, Sallow, Weakness.

During postmarketing surveillance which includes other dosage forms and other patient populations, the following adverse events were reported.

Symptoms consistent with an anaphylactoid or asthmatic process have been rarely (incidence rate of about 0.002%) reported. Rash, urticaria, and photosensitivity reactions have also been reported.

Localized reactions including induration and abscess have been reported at the site of injection.

Symptoms consistent with fibromyalgia (e.g., joint and muscle pain, headaches, sleep disorders, gastrointestinal distress, and shortness of breath) have been reported individually and collectively.

Cardiovascular System ¾ Hypotension; Gastrointestinal System ¾ Hepatic dysfunction; Hemic and Lymphatic System ¾ Decreased WBC; Integumentary System ¾ Hair growth; Central/Peripheral Nervous System ¾ Spinal fracture/paralysis, Hearing disorder; Miscellaneous ¾ Hard nodule in throat, Weight gain, Increased uric acid; Musculoskeletal System ¾ Tenosynovitis-like symptoms; Respiratory System ¾Respiratory disorders.

Changes in Bone Density: Decreased bone density has been reported in the medical literature in men who have had orchiectomy or who have been treated with an LH-RH agonist analog. In a clinical trial, 25 men with prostate cancer, 12 of whom had been treated previously with leuprolide acetate for at least six months, underwent bone density studies as a result of pain. The leuprolide-treated group had lower bone density scores than the nontreated control group. It can be anticipated that long periods of medical castration in men will have effects on bone density.

Pituitary apoplexy: During post-marketing surveillance, rare cases of pituitary apoplexy (a clinical syndrome secondary to infarction of the pituitary gland) have been reported after the administration of gonadotropin-releasing hormone agonists. In a majority of these cases, a pituitary adenoma was diagnosed, with a majority of pituitary apoplexy cases occurring within 2 weeks of the first dose, and some within the first hour. In these cases, pituitary apoplexy has presented as sudden headache, vomiting, visual changes, ophthalmoplegia, altered mental status, and sometimes cardiovascular collapse. Immediate medical attention has been required.

See other LUPRON DEPOT and LUPRON INJECTION package inserts for other events reported in the same and different patient populations.

See CLINICAL PHARMACOLOGY, Pharmacokinetics section.

Drug/Laboratory Test Interactions: Administration of leuprolide acetate in therapeutic doses results in suppression of the pituitary-gonadal system. Normal function is usually restored within 4 to 12 weeks after treatment is discontinued.

Initially, LUPRON, like other LH-RH agonists, causes increases in serum levels of testosterone. Transient worsening of symptoms, or the occurrence of additional signs and symptoms of prostate cancer, may occasionally develop during the first few weeks of LUPRON treatment. A small number of patients may experience a temporary increase in bone pain, which can be managed symptomatically. As with other LH-RH agonists, isolated cases of ureteral obstruction and spinal cord compression have been observed, which may contribute to paralysis with or without fatal complications.

Safe use of leuprolide acetate in pregnancy has not been established clinically. Before starting treatment with LUPRON, pregnancy must be excluded (see CONTRAINDICATIONS section).

Periodic monitoring of serum testosterone and prostate-specific antigen (PSA) levels is recommended, especially if the anticipated clinical or biochemical response to treatment has not been achieved. It should be noted that results of testosterone determinations are dependent on assay methodology. It is advisable to be aware of the type and precision of the assay methodology to make appropriate clinical and therapeutic decisions.

Patients with metastatic vertebral lesions and/or with urinary tract obstruction should be closely observed during the first few weeks of therapy (see WARNINGS and ADVERSE REACTIONS sections).

Patients with known allergies to benzyl alcohol, an ingredient of the drug's vehicle, may present symptoms of hypersensitivity, usually local, in the form of erythema and induration at the injection site.

INFORMATION FOR PATIENTS

See INFORMATION FOR PATIENTS which appears after the REFERENCE section.

Laboratory Tests: Response to leuprolide acetate should be monitored by measuring serum levels of testosterone and prostate-specific antigen (PSA). In the majority of patients, testosterone levels increased above baseline during the first week, declining thereafter to baseline levels or below by the end of the second week of treatment. Castrate levels were reached within two to four weeks and once attained were maintained for as long as drug administration continued.

Carcinogenesis, Mutagenesis, Impairment of Fertility: Two-year carcinogenicity studies were conducted in rats and mice. In rats, a dose-related increase of benign pituitary hyperplasia and benign pituitary adenomas was noted at 24 months when the drug was administered subcutaneously at high daily doses (0.6 to 4 mg/kg). There was a significant but not dose-related increase of pancreatic islet-cell adenomas in females and of testicular interstitial cell adenomas in males (highest incidence in the low dose group). In mice no pituitary abnormalities were observed at a dose as high as 60 mg/kg for two years. Patients have been treated with leuprolide acetate for up to three years with doses as high as 10 mg/day and for two years with doses as high as 20 mg/day without demonstrable pituitary abnormalities.

Mutagenicity studies have been performed with leuprolide acetate using bacterial and mammalian systems. These studies provided no evidence of a mutagenic potential.

Clinical and pharmacologic studies in adults (≥ 18 years) with leuprolide acetate and similar analogs have shown full reversibility of fertility suppression when the drug is discontinued after continuous administration for periods of up to 24 weeks. However, no clinical studies have been conducted with leuprolide acetate to assess the reversibility of fertility suppression.

Pregnancy, Teratogenic Effects: Pregnancy Category X (see CONTRAINDICATIONS and WARNINGS sections). When administered on day 6 of pregnancy at test dosages of 0.00024, 0.0024, and 0.024 mg/kg (1/600 to 1/6 the human dose) to rabbits, LUPRON produced a dose-related increase in major fetal abnormalities. Similar studies in rats failed to demonstrate an increase in major fetal malformations throughout gestation. There was increased fetal mortality and decreased fetal weights with the two higher doses of LUPRON in rabbits and with the highest dose in rats. The effects on fetal mortality are expected consequences of the alterations in hormonal levels brought about by this drug.

Nursing Mothers: It is not known whether leuprolide acetate is excreted in human milk. LUPRON should not be used by nursing mothers.

Pediatric Use: See labeling for LUPRON INJECTION for Pediatric Use for the safety and effectiveness in children with central precocious puberty.

Geriatric Use: In the clinical trials for LUPRON INJECTION, the majority (69%) of subjects studied were at least 65 years of age. Therefore, the labeling reflects the pharmacokinetics, efficacy and safety of LUPRON in this population.

In rats subcutaneous administration of 250 to 500 times the recommended human dose, expressed on a per body weight basis, resulted in dyspnea, decreased activity, and local irritation at the injection site. There is no evidence at present that there is a clinical counterpart of this phenomenon. In early clinical trials with leuprolide acetate doses as high as 20 mg/day for up to two years caused no adverse effects differing from those observed with the 1 mg/day dose.

1. LUPRON INJECTION is contraindicated in patients known to be hypersensitive to GnRH, GnRH agonist analogs or any of the excipients in LUPRON INJECTION: Reports of anaphylactic reactions to synthetic GnRH (Factrel) or GnRH agonist analogs have been reported in the medical literature.¹

2. LUPRON is contraindicated in women who are or may become pregnant while receiving the drug. LUPRON may cause fetal harm when administered to a pregnant woman. Therefore, the possibility exists that spontaneous abortion may occur if the drug is administered during pregnancy. If this drug is administered during pregnancy or if the patient becomes pregnant while taking any formulation of LUPRON, the patient should be apprised of the potential hazard to the fetus.

REFERENCE

1. MacLeod TL, Eisen A, Sussman GL, et al: Anaphylactic reaction to synthetic luteinizing hormone-releasing hormone. Fertil Steril 1987 Sept;48(3):500-502.

Leuprolide acetate, an LH-RH agonist, acts as a potent inhibitor of gonadotropin secretion when given continuously and in therapeutic doses. Animal and human studies indicate that following an initial stimulation of gonadotropins, chronic administration of leuprolide acetate results in suppression of ovarian and testicular steroidogenesis. This effect is reversible upon discontinuation of drug therapy. Administration of leuprolide acetate has resulted in inhibition of the growth of certain hormone dependent tumors (prostatic tumors in Noble and Dunning male rats and DMBA-induced mammary tumors in female rats) as well as atrophy of the reproductive organs.

In humans, subcutaneous administration of single daily doses of leuprolide acetate results in an initial increase in circulating levels of luteinizing hormone (LH) and follicle stimulating hormone (FSH), leading to a transient increase in levels of the gonadal steroids (testosterone and dihydrotestosterone in males, and estrone and estradiol in pre-menopausal females). However, continuous daily administration of leuprolide acetate results in decreased levels of LH and FSH. In males, testosterone is reduced to castrate levels. In pre-menopausal females, estrogens are reduced to post-menopausal levels. These decreases occur within two to four weeks after initiation of treatment, and castrate levels of testosterone in prostatic cancer patients have been demonstrated for periods of up to five years.

Leuprolide acetate is not active when given orally.

Absorption Bioavailability by subcutaneous administration is comparable to that by intravenous administration.

Distribution The mean steady-state volume of distribution of leuprolide following intravenous bolus administration to healthy male volunteers was 27 L. In vitro binding to human plasma proteins ranged from 43% to 49%.

Metabolism In healthy male volunteers, a 1 mg bolus of leuprolide administered intravenously revealed that the mean systemic clearance was 7.6 L/h, with a terminal elimination half-life of approximately 3 hours based on a two compartment model. In rats and dogs, administration of ¹⁴C-labeled leuprolide was shown to be metabolized to smaller inactive peptides, a pentapeptide (Metabolite I), tripeptides (Metabolites II and III) and a dipeptide (Metabolite IV). These fragments may be further catabolized. The major metabolite (M-I) plasma concentrations measured in 5 prostate cancer patients reached maximum concentration 2 to 6 hours after dosing and were approximately 6% of the peak parent drug concentration. One week after dosing, mean plasma M-I concentrations were approximately 20% of mean leuprolide concentrations.

Excretion Following administration of LUPRON DEPOT 3.75 mg to 3 patients, less than 5% of the dose was recovered as parent and M-I metabolite in the urine.

Special Populations The pharmacokinetics of the drug in hepatically and renally impaired patients have not been determined.

Drug Interactions No pharmacokinetic-based drug-drug interaction studies have been conducted with leuprolide acetate. However, because leuprolide acetate is a peptide that is primarily degraded by peptidase and not by cytochrome P-450 enzymes as noted in specific studies, and the drug is only about 46% bound to plasma proteins, drug interactions would not be expected to occur.

In a controlled study comparing LUPRON 1 mg/day given subcutaneously to DES (diethylstilbestrol), 3 mg/day, the survival rate for the two groups was comparable after two years of treatment. The objective response to treatment was also similar for the two groups.

Be sure to consult your physician with any questions you may have or for information about LUPRON INJECTION (leuprolide acetate) and its use.

LUPRON INJECTION (leuprolide acetate) is chemically similar to gonadotropin releasing hormone (GnRH or LH-RH) a hormone which occurs naturally in your body.

Normally, your body releases small amounts of LH-RH and this leads to events which stimulate the production of sex hormones.

However, when you inject LUPRON INJECTION (leuprolide acetate), the normal events that lead to sex hormone production are interrupted and testosterone is no longer produced by the testes.

LUPRON must be injected because, like insulin which is injected by diabetics, LUPRON is inactive when taken by mouth.

If you were to discontinue the drug for any reason, your body would begin making testosterone again.

1. Wash hands thoroughly with soap and water.

2. If using a new bottle for the first time, flip off the plastic cover to expose the grey rubber stopper. Wipe metal ring and rubber stopper with an alcohol wipe each time you use LUPRON. Check the liquid in the container. If it is not clear or has particles in it, DO NOT USE IT. Exchange it at your pharmacy for another container.

3. Remove outer wrapping from one syringe. Pull plunger back until the tip of the plunger is at the 0.2 mL or 20 unit mark.

4. Take cover off needle. Push the needle through the center of the rubber stopper on the LUPRON bottle.

5. Push the plunger all the way in to inject air into the bottle.

6. Keep the needle in the bottle and turn the bottle upside down. Check to make sure the tip of the needle is in the liquid. Slowly pull back on the plunger, until the syringe fills to the 0.2 mL or 20 unit mark.

7. Toward the end of a two-week period, the amount of LUPRON left in the bottle will be small. Take special care to hold the bottle straight and to keep the needle tip in liquid while pulling back on the plunger.

8. Keeping the needle in the bottle and the bottle upside down, check for air bubbles in the syringe. If you see any, push the plunger slowly in to push the air bubble back into the bottle. Keep the tip of the needle in the liquid and pull the plunger back again to fill to the 0.2 mL or 20 unit mark.

9. Do this again if necessary to eliminate air bubbles.

10. To protect your skin, inject each daily dose at a different body spot.

11. Choose an injection spot. Cleanse the injection spot with another alcohol wipe.

12. Hold the syringe in one hand. Hold the skin taut, or pull up a little flesh with the other hand, as you were instructed.

13. Holding the syringe as you would a pencil, thrust the needle all the way into the skin at a 90° angle. Push the plunger to administer the injection.

14. Hold an alcohol wipe down on your skin where the needle is inserted and withdraw the needle at the same angle it was inserted.

15. Use the disposable syringe only once and dispose of it properly as you were instructed. Needles thrown into a garbage bag could accidentally stick someone. NEVER LEAVE SYRINGES, NEEDLES OR DRUGS WHERE CHILDREN CAN REACH THEM.

SOME SPECIAL ADVICE

· You may experience hot flashes when using LUPRON INJECTION (leuprolide acetate). During the first few weeks of treatment you may experience increased bone pain, increased difficulty in urinating, and less commonly but most importantly, you may experience the onset or aggravation of nerve symptoms. In any of these events, discuss the symptoms with your doctor. Like other treatment options, LUPRON may cause impotence. Notify your doctor if you develop new or worsened symptoms after beginning LUPRON treatment.

· You may experience some irritation at the injection site, such as burning, itching or swelling. These reactions are usually mild and go away. If they do not, tell your doctor.

· If you have experienced an allergic reaction to other drugs like LUPRON, you should not use this drug.

· Do not stop taking your injections because you feel better. You need an injection every day to make sure LUPRON keeps working for you.

· If you need to use an alternate to the syringe supplied with LUPRON, low-dose insulin syringes should be utilized.

· When the drug level gets low, take special care to hold the bottle straight up and down and to keep the needle tip in liquid while pulling back on the plunger.

· Do not try to get every last drop out of the bottle. This will increase the possibility of drawing air into the syringe and getting an incomplete dose. Some extra drug has been provided so that you can withdraw the recommended number of doses.

· Tell your pharmacist when you will need LUPRON so it will be at the pharmacy when you need it.

· Store below 77°F (25°C). Do not store near a radiator or other very warm place. Do not freeze. Protect from light; store vial in carton until use.

· Do not leave your drug or hypodermic syringes where anyone can pick them up.

· Keep this and all other medications out of reach of children.

IMPORTANT NOTE: This is a summary and does not contain all possible information about this product. For complete information about this product or your specific health needs, ask your health care professional. Always seek the advice of your health care professional if you have any questions about this product or your medical condition. This information is not intended as individual medical advice and does not substitute for the knowledge and judgment of your health care professional. This information does not contain any assurances that this product is safe, effective, or appropriate for you.

LEUPROLIDE - INJECTION

(LEW-pro-lide)

COMMON BRAND NAME(S): Lupron

USES: Leuprolide is used to treat advanced prostate cancer in men. It is not a cure. Most types of prostate cancer need the male hormone testosterone to grow and spread. Leuprolide works by reducing the amount of testosterone that the body makes. This helps slow or stop the growth of cancer cells and helps relieve symptoms such as painful/difficult urination.

Leuprolide is also used to stop early puberty (precocious puberty) in children. It helps to delay sexual development (e.g., growth of the breasts/testicles) and the start of menstrual periods. It also helps slow down the rate of early bone growth so that the chances for reaching normal adult height are increased. Leuprolide works by decreasing the amount of sex hormones that a child's body makes (estrogen in girls, testosterone in boys).

OTHER USES: This section contains uses of this drug that are not listed in the approved professional labeling for the drug but that may be prescribed by your health care professional. Use this drug for a condition that is listed in this section only if it has been so prescribed by your health care professional.

Other leuprolide products may also be used to treat disorders of the uterus (e.g., endometriosis, fibroids). In females, leuprolide reduces the amount of estrogen that the body makes.

HOW TO USE: This medication is given as an injection under the skin (subcutaneously), usually once a day or as directed by your doctor.

In children, the dosage is based on weight and response to therapy. The doctor should consider stopping treatment before age 11 for girls and age 12 for boys. Consult the doctor for details.

If you are directed to inject this medication yourself, learn all preparation and usage instructions in the product package. Learn how to store and discard needles and medical supplies safely. If any of the information is unclear, consult your doctor or pharmacist.

Before using, check this product visually for particles or discoloration. If either is present, do not use the liquid. Change the location of the injection site each time to avoid problem areas under the skin.

Use this medication regularly to get the most benefit from it. To help you remember, use it at the same time each day.

Inform your doctor if your symptoms do not improve or if they worsen.

SIDE EFFECTS: Mild burning/pain/bruising at the injection site, hot flashes (flushing), increased sweating, night sweats, tiredness, headache, upset stomach, breast changes, acne, joint/muscle aches, trouble sleeping, reduced sexual interest, vaginal discomfort/dryness, vaginal bleeding, swelling of the ankles/feet, increased urination at night, or dizziness may occur. If any of these effects persist or worsen, tell your doctor or pharmacist promptly.

Infrequently in men, shrinking of the testicles, breast tenderness/swelling, and reduced sexual interest/ability may also occur as a result of lowered testosterone levels. Talk to your doctor if these effects occur.

In girls, when this medication is used regularly, it is expected that the menstrual period will stop (or decrease to light bleeding/spotting during the first 2 months). Tell your doctor promptly if regular periods continue after 2 months of treatment with leuprolide.

Remember that your doctor has prescribed this medication because he or she has judged that the benefit to you is greater than the risk of side effects. Many people using this medication do not have serious side effects.

During the first few weeks of treatment, your hormone levels will actually increase before they decrease. This is a normal response by your body to this drug. This may result in a temporary increase in your symptoms for a few weeks.

In men, an increase in testosterone levels at the beginning of treatment may sometimes result in new or worsening symptoms for a few weeks. If you have prostate cancer that has spread to the spine or caused urinary blockage, you may require closer monitoring by your doctor, especially when you first start treatment. Tell your doctor immediately if you experience any of the following serious side effects: bone pain, numbness/tingling/weakness of the arms/legs, blood in the urine, painful/difficult urination, unusual weakness, inability to move.

Tell your doctor immediately if any of these unlikely but serious side effects occur: mental/mood changes (e.g., depression, thoughts of suicide, mood swings, aggression in children), new/worsening bone pain (in adults), easily broken bones (in adults).

Rarely, a very serious problem with your pituitary gland (pituitary apoplexy) may occur, usually in the first hour to 2 weeks after your first injection. Seek immediate medical attention if any of these very serious side effects occur: sudden severe headache, sudden severe mental/mood changes (e.g., severe confusion, difficulty concentrating), vision changes, severe vomiting, fainting.

A very serious allergic reaction to this drug is rare. However, seek immediate medical attention if you notice any symptoms of a serious allergic reaction, including: rash, itching, swelling, severe dizziness, trouble breathing.

This is not a complete list of possible side effects. If you notice other effects not listed above, contact your doctor or pharmacist.

Contact your doctor for medical advice about side effects. The following numbers do not provide medical advice, but in the US you may report side effects to the Food and Drug Administration (FDA) at 1-800-FDA-1088. In Canada, you may call Health Canada at 1-866-234-2345.

PRECAUTIONS: Before using leuprolide, tell your doctor or pharmacist if you are allergic to it; or to the preservative benzyl alcohol; or if you have any other allergies.

Before using this medication, tell your doctor or pharmacist your medical history.

In adults, leuprolide may weaken your bones and increase your risk for bone loss (osteoporosis) if used for a long time. Before using this medication, tell your doctor or pharmacist if you have osteoporosis or if you have any of the following risk factors for osteoporosis: long-term alcohol use, smoking, family history of osteoporosis and broken bones, use of certain medications (e.g., corticosteroids such as prednisone, certain anti-seizure drugs such as phenytoin).

This drug may make you dizzy. Use caution while driving, using machinery, or doing any activity that requires alertness. Limit alcoholic beverages.

Leuprolide must not be used during pregnancy. It may harm an unborn baby. If you become pregnant or think you may be pregnant, inform your doctor immediately. Consult your doctor for more details and to discuss reliable forms of birth control. Non-hormonal birth control methods (e.g., condoms, diaphragm with spermicide) are recommended during treatment with leuprolide.

It is not known if leuprolide passes into breast milk. Because the effects of leuprolide on a nursing infant are unknown, breast-feeding is not recommended. Consult your doctor before breast-feeding.

DRUG INTERACTIONS: Your doctor or pharmacist may already be aware of any possible drug interactions and may be monitoring you for them. Do not start, stop, or change the dosage of any medicine before checking with your doctor or pharmacist first.

Before using this medication, tell your doctor or pharmacist of all prescription and nonprescription/herbal products you may use.

Keep a list of all your medications with you, and share the list with your doctor and pharmacist.

OVERDOSE: If overdose is suspected, contact your local poison control center or emergency room immediately. US residents can call the US National Poison Hotline at 1-800-222-1222. Canada residents can call a provincial poison control center.

NOTES: Do not share this medication with others.

Laboratory and/or medical tests (e.g., hormone levels, PSA blood test for men, bone tests) should be performed periodically to monitor your progress. Consult your doctor for more details.

MISSED DOSE: It is very important that you do not miss any doses. However, if you miss a dose, use it as soon as you remember. If it is near the time of the next dose, skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up.

STORAGE: Store below 77 degrees F (25 degrees C) away from light and moisture. Do not freeze. Keep all medicines away from children and pets.

Do not flush medications down the toilet or pour them into a drain unless instructed to do so. Properly discard this product when it is expired or no longer needed. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product.

MEDICAL ALERT: Your condition can cause complications in a medical emergency. For information about enrolling in MedicAlert, call 1-800-854-1166 (USA) or 1-800-668-1507 (Canada).

Information last revised July 2008 Copyright(c) 2008 First DataBank, Inc.