Lupron Depot (Leuprolide Acetate for Depot Suspension)
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Lupron Depot (Leuprolide Acetate for Depot Suspension)

Lupron Depot
(leuprolide acetate) for Depot Suspension

DRUG DESCRIPTION

Leuprolide acetate is a synthetic nonapeptide analog of naturally occurring gonadotropin-releasing hormone (GnRH). The analog possesses greater potency than the natural hormone. The chemical name is 5-oxo-Lprolyl-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 Depot (leuprolide acetate for depot suspension) Structural Formula Illustration

LUPRON DEPOT 22.5 mg for 3-month administration is available in a prefilled dual-chamber syringe containing sterile lyophilized microspheres which, when mixed with diluent, become a suspension intended as an intramuscular injection to be given ONCE EVERY 12 WEEKS.

The front chamber of LUPRON DEPOT 22.5 mg for 3-month administration prefilled dual-chamber syringe contains leuprolide acetate (22.5 mg), polylactic acid (198.6 mg) and D-mannitol (38.9 mg). The second chamber of diluent contains carboxymethylcellulose sodium (7.5 mg), D-mannitol (75.0 mg), polysorbate 80 (1.5 mg), water for injection, USP, and glacial acetic acid, USP to control pH.

LUPRON DEPOT 30 mg for 4-month administration is available in a prefilled dual-chamber syringe containing sterile lyophilized microspheres which, when mixed with diluent, become a suspension intended as an intramuscular injection to be given ONCE EVERY 16 WEEKS.

The front chamber of LUPRON DEPOT 30 mg for 4-month administration prefilled dual-chamber syringe contains leuprolide acetate (30 mg), polylactic acid (264.8 mg) and D-mannitol (51 mg). The second chamber of diluent contains carboxymethylcellulose sodium (7.5 mg), D-mannitol (75.0 mg), polysorbate 80 (1.5 mg), water for injection, USP, and glacial acetic acid, USP to control pH.

LUPRON DEPOT 45 mg for 6-month administration is available in a prefilled dual-chamber syringe containing sterile lyophilized microspheres which, when mixed with diluent, become a suspension intended as an intramuscular injection to be given ONCE EVERY 24 WEEKS.

The front chamber of LUPRON DEPOT 45 mg for 6-month administration prefilled dual-chamber syringe contains leuprolide acetate (45 mg), polyactic acid (169.9 mg), D-mannitol (39.7 mg), and stearic acid (10.1 mg). The second chamber of diluent contains carboxymethylcellulose sodium (7.5 mg), D-mannitol (75.0 mg), polysorbate 80 (1.5 mg), water for injection, USP, and glacial acetic acid, USP to control pH.

During the manufacture of LUPRON DEPOT 22.5 mg for 3-month administration, 30 mg for 4-month administration, and 45 mg for 6-month administration, acetic acid is lost, leaving the peptide.

What are the possible side effects of leuprolide (Eligard, Lupron, Lupron Depot, Lupron Depot-Gyn, Lupron Depot-Ped)?

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have a serious side effect such as:

  • bone pain, loss of movement in any part of your body;
  • swelling, rapid weight gain;
  • pain, burning, stinging, bruising, or redness where the medication was injected;
  • feeling like you might pass out;
  • painful or difficult urination;
  • urinating more...

Read All Potential Side Effects and See Pictures of Lupron Depot »

What are the precautions when taking leuprolide acetate for depot suspension (Lupron Depot)?

Before using leuprolide, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: diabetes, heart disease (such as heart attack), stroke, high cholesterol, family history of sudden cardiac death.

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...

Read All Potential Precautions of Lupron Depot »

Last reviewed on RxList: 8/3/2012
This monograph has been modified to include the generic and brand name in many instances.

INDICATIONS

LUPRON DEPOT 22.5 mg for 3–month administration, 30 mg for 4–month administration, and 45 mg for 6– month administration (leuprolide acetate) are indicated in the palliative treatment of advanced prostatic cancer.

LUPRON DEPOT is a gonadotropin releasing hormone (GnRH) agonist.

DOSAGE AND ADMINISTRATION

LUPRON DEPOT must be administered under the supervision of a physician.

Table 1 : LUPRON DEPOT Recommended Dosing

Dosage 22.5 mg for 3-Month Administration 30 mg for 4-Month Administration 45 mg for 6-Month Administration
Recommended dose 1 injection every 12 weeks 1 injection every 16 weeks 1 injection every 24 weeks

LUPRON DEPOT 22.5 mg for 3-Month Administration

The recommended dose of LUPRON DEPOT 22.5 mg for 3-month administration is one injection every 12 weeks. Due to different release characteristics, a fractional dose, or a combination of doses of this depot formulation is not equivalent to the same dose of the monthly formulation and should not be given.

Incorporated in a depot formulation, the lyophilized microspheres are to be reconstituted and administered every 12 weeks as a single intramuscular injection.

For optimal performance of the prefilled dual chamber syringe (PDS), read and follow the instructions in Section 2.4.

LUPRON DEPOT 30 mg for 4-Month Administration

The recommended dose of LUPRON DEPOT 30 mg for 4-month administration is one injection every 16 weeks. Due to different release characteristics, a fractional dose, or a combination of doses of this depot formulation is not equivalent to the same dose of the monthly formulation and should not be given.

Incorporated in a depot formulation, the lyophilized microspheres are to be reconstituted and administered every 16 weeks as a single intramuscular injection.

For optimal performance of the prefilled dual chamber syringe (PDS), read and follow the instructions in Section 2.4.

LUPRON DEPOT 45 mg for 6-Month Administration

The recommended dose of LUPRON DEPOT 45 mg for 6-month administration is one injection every 24 weeks. Due to different release characteristics, a fractional dose, or a combination of doses of this depot formulation is not equivalent to the same dose of the monthly formulation and should not be given.

Incorporated in a depot formulation, the lyophilized microspheres are to be reconstituted and administered every 24 weeks as a single intramuscular injection.

For optimal performance of the prefilled dual chamber syringe (PDS), read and follow the instructions in Section 2.4.

Administration of Injection

  • The lyophilized microspheres are to be reconstituted and administered as a single intramuscular injection.
  • Since LUPRON DEPOT does not contain a preservative, the suspension should be injected immediately or discarded if not used within two hours.
  • As with other drugs administered by injection, the injection site should be varied periodically.

1. The LUPRON DEPOT powder should be visually inspected and the syringe should NOT BE USED if clumping or caking is evident. A thin layer of powder on the wall of the syringe is considered normal prior to mixing with the diluent. The diluent should appear clear.

2. To prepare for injection, screw the white plunger into the end stopper until the stopper begins to turn.

screw the white plunger into the end stopper - Illustration

3. Hold the syringe UPRIGHT. Release the diluent by SLOWLY PUSHING (6 to 8 seconds) the plunger until the first stopper is at the blue line in the middle of the barrel.

Hold the syringe upright -  Illustration

4. Keep the syringe UPRIGHT. Gently mix the microspheres (powder) thoroughly to form a uniform suspension. The suspension will appear milky. If the powder adheres to the stopper or caking/clumping is present, tap the syringe with your finger to disperse. DO NOT USE if any of the powder has not gone into suspension.

Gently mix the microspheres - Illustration

5. Hold the syringe UPRIGHT. With the opposite hand pull the needle cap upward without twisting.

6. Keep the syringe UPRIGHT. Advance the plunger to expel the air from the syringe.

7. After cleaning the injection site with an alcohol swab, insert the needle completely at a 90 degree angle.

Insert the needle completely at a 90 degree angle -  Illustration

NOTE: Aspirated blood would be visible just below the luer lock connection if a blood vessel is accidentally penetrated. If present, blood can be seen through the transparent LuproLoc® safety device. If blood is present remove the needle immediately. Do not inject the medication

Luer lock connection - Illustration

8. Inject the entire contents of the syringe intramuscularly at the time of reconstitution. The suspension settles very quickly following reconstitution; therefore, LUPRON DEPOT should be mixed and used immediately.

After Injection

9. Withdraw the needle. Immediately activate the LuproLoc® safety device by pushing the arrow forward with the thumb or finger, as illustrated, until the device is fully extended and a CLICK is heard or felt.

Activate the LuproLoc® safety device - Illustration

Additional Information

  • Please see the handling information in the Reference.
  • Dispose of the syringe according to local regulations/procedures.

HOW SUPPLIED

Dosage Forms And Strengths

LUPRON DEPOT 22.5 mg for 3-month administration, 30 mg for 4-month administration, and 45 mg for 6month administration are each supplied as a kit with prefilled dual chamber syringe.

Storage And Handling

Each LUPRON DEPOT 22.5 mg for 3-month administration (NDC 0074-3346-03), 30 mg for 4-month administration (NDC 0074-3683-03), 45 mg for 6-month administration (NDC 0074-3473-03) contains:

  • one prefilled dual-chamber syringe containing needle with LuproLoc® safety device
  • one plunger
  • two alcohol swabs
  • a complete prescribing information enclosure

The prefilled dual-chamber syringe contains sterile lyophilized microspheres of leuprolide acetate incorporated in a biodegradable lactic acid polymer.

When mixed with 1.5 mL of accompanying diluent, LUPRON DEPOT 22.5 mg for 3-month administration is administered as a single intramuscular injection EVERY 12 WEEKS.

When mixed with 1.5 mL of accompanying diluent, LUPRON DEPOT 30 mg for 4-month administration is administered as a single intramuscular injection EVERY 16 WEEKS. When mixed with 1.5 mL of accompanying diluent, LUPRON DEPOT 45 mg for 6-month administration is administered as a single intramuscular injection EVERY 24 WEEKS.

Store at 25°C (77°F); excursions permitted to 15–30°C (59–86°F) [See USP Controlled Room Temperature].

REFERENCES

1. NIOSH Alert: Preventing occupational exposures to antineoplastic and other hazardous drugs in healthcare settings. 2004. U.S. Department of Health and Human Services, Public Health Service, Centers for Disease Control and Prevention, National Institute for Occupational Safety and Health, DHHS (NIOSH) Publication No. 2004-165.

2. OSHA Technical Manual, TED 1-0.15A, Section VI: Chapter 2. Controlling Occupational Exposure to Hazardous Drugs. OSHA, 1999. http://www.osha.gov/dts/osta/otm/otm_vi/otm_vi_2.html

3. American Society of Health-System Pharmacists. ASHP guidelines on handling hazardous drugs. Am J Health-Syst Pharm. 2006; 63; 1172-1193.

4. Polovich, M., White, J.M., & Kelleher, L.O. (eds.) 2005. Chemotherapy and biotherapy guidelines and recommendations for practice (2nd Ed.) Pittsburgh, PA: Oncology Nursing Society.

Manufactured for Abbott Laboratories North Chicago, IL 60064 by Takeda Pharmaceutical Company Limited Osaka, Japan 540-8645. Rev. 07/2012

Last reviewed on RxList: 8/3/2012
This monograph has been modified to include the generic and brand name in many instances.

SIDE EFFECTS

Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice.

LUPRON DEPOT 22.5 mg for 3-Month Administration

Clinical Trials

In two clinical trials of LUPRON DEPOT 22.5 mg for 3-month administration, the following adverse reactions were reported to have a possible or probable relationship to drug as ascribed by the treating physician in 5% or more of the patients receiving the drug. Often, causality is difficult to assess in patients with metastatic prostate cancer. Reactions considered not drug-related are excluded.

Table 2: Adverse Reactions Reported in ≥ 5% of Patients

LUPRON DEPOT 22.5 mg for 3-Month Administration
Body System/Reaction N=94 (%)
Body As A Whole
Asthenia 7 (7.4)
General Pain 25 (26.6)
Headache 6 (6.4)
Injection Site Reaction 13 (13.8)
Cardiovascular System
Hot flashes/Sweats 55 (58.5)
Digestive System
GI Disorders 15 (16)
Musculoskeletal System
Joint Disorders 11 (11.7)
Central/Peripheral Nervous System
Dizziness/Vertigo 6 (6.4)
Insomnia/Sleep Disorders 8 (8.5)
Neuromuscular Disorders 9 (9.6)
Respiratory System
Respiratory Disorders 6 (6.4)
Skin and Appendages
Skin Reaction 8 (8.5)
Urogenital System
Testicular Atrophy 19 (20.2)
Urinary Disorders 14 (14.9 )

In these same studies, the following adverse reactions were reported in less than 5% of the patients on LUPRON DEPOT 22.5 mg for 3-month administration.

Body As A Whole -Enlarged abdomen, Fever

Cardiovascular System -Arrhythmia, Bradycardia, Heart failure, Hypertension, Hypotension, Varicose vein

Digestive System -Anorexia, Duodenal ulcer, Increased appetite, Thirst/dry mouth

Hemic and Lymphatic System -Anemia, Lymphedema

Metabolic and Nutritional Disorders -Dehydration, Edema

Central/Peripheral Nervous System -Anxiety, Delusions, Depression, Hypesthesia, Libido decreased*, Nervousness, Paresthesia

Respiratory System -Epistaxis, Pharyngitis, Pleural effusion, Pneumonia

Special Senses -Abnormal vision, Amblyopia, Dry eyes, Tinnitus

Urogenital System -Gynecomastia, Impotence*, Penis disorders, Testis disorders.

* Physiologic effect of decreased testosterone.

Laboratory

Abnormalities of certain parameters were observed, but are difficult to assess in this population. The following were recorded in ≥ 5% of patients: Increased BUN, Hyperglycemia, Hyperlipidemia (total cholesterol, LDL-cholesterol, triglycerides), Hyperphosphatemia, Abnormal liver function tests, Increased PT, Increased PTT. Additional laboratory abnormalities reported were: Decreased platelets, Decreased potassium and Increased WBC.

LUPRON DEPOT 30 mg for 4-Month Administration

Clinical Trials

The 4-month formulation of LUPRON DEPOT 30 mg was utilized in clinical trials that studied the drug in 49 nonorchiectomized prostate cancer patients for 32 weeks or longer and in 24 orchiectomized prostate cancer patients for 20 weeks.

In the above described clinical trials, the following adverse reactions were reported in ≥ 5% of the patients during the treatment period regardless of causality.

Table 3: Adverse Events Regardless of Causality Reported in ≥ 5% of Patients

LUPRON DEPOT 30 mg for 4-Month Administration
Body System/Events Non orchiectomized Orchiectomized
Study 013 Study 012
N=49 (%) N=24 (%)
Body As a Whole
Asthenia 6 (12.2) 1 (4.2)
Flu Syndrome 6 (12.2) 0 (0.0)
General Pain 16 (32.7) 1 (4.2)
Headache 5 (10.2) 1 (4.2)
Injection Site Reaction 4 (8.2) 9 (37.5)
Cardiovascular System
Hot flashes/Sweats 23 (46.9) 2 (8.3)
Digestive System
GI Disorders 5 (10.2) 3 (12.5)
Metabolic and Nutritional Disorders
Dehydration 4 (8.2) 0 (0.0)
Edema 4 (8.2) 5 (20.8)
Musculoskeletal System
Joint Disorder 8 (16.3) 1 (4.2)
Myalgia 4 (8.2) 0 (0.0)
Nervous System
Dizziness/Vertigo 3 (6.1) 2 (8.3)
Neuromuscular Disorders 3 (6.1) 1 (4.2)
Paresthesia 4 (8.2) 1 (4.2)
Respiratory System
Respiratory Disorder 4 (8.2) 1 (4.2)
Skin and Appendages
Skin Reaction 6 (12.2) 0 (0.0)
Urogenital System
Urinary Disorders 5 (10.2) 4 (16.7)

In these same studies, the following adverse reactions were reported in less than 5% of the patients on LUPRON DEPOT 30 mg for 4-month administration.

Body As a Whole -Abscess, Accidental injury, Allergic reaction, Cyst, Fever, Generalized edema, Hernia, Neck pain, Neoplasm

Cardiovascular System -Atrial fibrillation, Deep thrombophlebitis, Hypertension

Digestive System -Anorexia, Eructation, Gastrointestinal hemorrhage, Gingivitis, Gum hemorrhage, Hepatomegaly, Increased appetite, Intestinal obstruction, Periodontal abscess

Hemic and Lymphatic System -Lymphadenopathy

Metabolic and Nutritional Disorders -Healing abnormal, Hypoxia, Weight loss

Musculoskeletal System -Leg cramps, Pathological fracture, Ptosis

Nervous System -Abnormal thinking, Amnesia, Confusion, Convulsion, Dementia, Depression,

Insomnia/sleep disorders, Libido decreased*, Neuropathy, Paralysis

Respiratory System -Asthma, Bronchitis, Hiccup, Lung disorder, Sinusitis, Voice alteration

Skin and Appendages -Herpes zoster, Melanosis

Urogenital System -Bladder carcinoma, Epididymitis, Impotence*, Prostate disorder, Testicular atrophy*, Urinary incontinence, Urinary tract infection.

* Physiologic effect of decreased testosterone.

Laboratory

Abnormalities of certain parameters were observed, but their relationship to drug treatment is difficult to assess in this population. The following were recorded in ≥ 5% of patients: Decreased bicarbonate, Decreased hemoglobin/hematocrit/RBC, Hyperlipidemia (total cholesterol, LDL-cholesterol, triglycerides), Decreased HDL-cholesterol, Eosinophilia, Increased glucose, Increased liver function tests (ALT, AST, GGTP, LDH), Increased phosphorus. Additional laboratory abnormalities were reported: Increased BUN and PT, Leukopenia, Thrombocytopenia, Uricaciduria.

LUPRON DEPOT 45 mg for 6-Month Administration

Clinical Trials

One open label, multicenter study was conducted with LUPRON DEPOT 45 mg for 6-month administration in 151 prostate cancer patients. Patients were treated for 48 weeks, with 139/151 receiving two injections 24 weeks apart.

In the above described clinical trial, the following adverse events were reported in ≥ 5% of the patients during the treatment period. The Table 4 includes all adverse events reported in ≥ 5% of patients as well as the incidences of these adverse events that were considered, by the treating physician, to have a definite or possible relationship to LUPRON.

Table 4: Adverse Events in ≥ 5% of Patients

LUPRON DEPOT 45 mg for 6-Month Administration
Adverse Event Treatment Emergent Treatment Related
N = 151 (%) N = 151 (%)
Hot Flush/Flushing 89 58.9 88 58.3
Injection Site Pain/Discomfort 29 19.2 16 10.6
Upper Respiratory Tract Infection/Influenza-like Illness1 32 21.2 0 0
Fatigue/Lethargy 20 13.2 18 11.9
Constipation 15 9.9 5 3.3
Arthralgia 14 9.3 2 1.3
Insomnia/Sleep Disorder 13 8.6 5 3.3
Headache/Sinus Headache 12 7.9 3 2
Musculoskeletal Pain/ Myalgia 12 7.9 3 2
Second Primary Neoplasm2 11 7.3 0 0
Cough 10 6.6 2 1.3
Hematuria/Hemorrhagic Cystitis 10 6.6 0 0
Hypertension/BP Increased 10 6.6 3 2
Rash 9 6 3 2
Dysuria 9 6 1 0.7
Urinary Tract Infection/Cystitis 9 6 0 0
Anemia/Hemoglobin Decreased 10 6.6 2 1.3
Back Pain 8 5.3 0 0
COPD 8 5.3 0 0
Dizziness 8 5.3 3 2
Dyspnea/Dyspnea on Exertion 8 5.3 2 1.3
Nocturia 8 5.3 2 1.3
Peripheral/Pitting Edema 8 5.3 2 1.3
Coronary Artery Disease/Angina 8 5.3 1 0.7
1Includes influenza, nasal congestion, nasopharyngitis, rhinorrhea, upper respiratory tract infection, and viral upper respiratory tract infection
2Includes basal cell carcinoma, bladder transitional cell carcinoma, lung neoplasm, malignant melanoma, nonHodgkin's lymphoma, and squamous cell carcinoma

The following adverse events led to discontinuation; fatigue, hot flush, second primary neoplasm, asthenia, coronary artery disease, constipation, hyperkalemia, and sleep disorder. Serious adverse events in ≥ 2% of patients, regardless of causality, included chronic obstructive pulmonary disease, coronary artery disease/angina, cerebrovascular accident/transient ischemic attack, pneumonia, and second primary neoplasms.

Laboratory

At baseline, 13.9% of patients had a CTCAE v4.0 grade 1 or 2 decreased hemoglobin. During the study, 42.4% of subjects had grade 1 decreased hemoglobin (10 - < 12-5 g/dL), 2.0% had grade 2 ( 8 - < 10 g/dL) and 1.3% of subjects had grade 3 or 4 ( < 8 g/dL). Likewise, 28.5% of patients had a grade 1 or 2 increased cholesterol at baseline while 55.0% had grade 1 increased cholesterol ( > 199-300 mg/dL), 3.3% had a grade 2 increase ( > 300-400 mg/dL), and 0.7% of subjects had grade 3 ( > 400 mg/dL) during the study.

Postmarketing

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

Like other drugs in this class, mood swings, including depression, have been reported. There have been very rare reports of suicidal ideation and attempt. Many, but not all, of these patients had a history of depression or other psychiatric illness. Patients should be counseled on the possibility of development or worsening of depression during treatment with LUPRON.

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.

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 a GnRH 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.

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 – Hypotension, Myocardial infarction, Pulmonary embolism

Respiratory, thoracic and mediastinal disorder – Interstitial lung disease

Hemic and Lymphatic System -Decreased WBC

Central/Peripheral Nervous System -Convulsion, Peripheral neuropathy, Spinal fracture/paralysis

Endocrine System – Diabetes

Musculoskeletal System -Tenosynovitis-like symptoms

Urogenital System -Prostate pain

See other LUPRON DEPOT and LUPRON Injection package inserts for other reactions reported in women and pediatric populations.

Read the Lupron Depot (leuprolide acetate for depot suspension) Side Effects Center for a complete guide to possible side effects »

DRUG INTERACTIONS

No pharmacokinetic-based drug-drug interaction studies have been conducted with LUPRON DEPOT. 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.

See CLINICAL PHARMACOLOGY.

Drug/Laboratory Test Interactions

Administration of LUPRON DEPOT in therapeutic doses results in suppression of the pituitary-gonadal system. Normal function is usually restored within three months after treatment is discontinued. Due to the suppression of the pituitary-gonadal system by LUPRON DEPOT, diagnostic tests of pituitary gonadotropic and gonadal functions conducted during treatment and up to three months after discontinuation of LUPRON DEPOT may be affected.

Last reviewed on RxList: 8/3/2012
This monograph has been modified to include the generic and brand name in many instances.

WARNINGS

Included as part of the PRECAUTIONS section.

PRECAUTIONS

Tumor Flare

Initially, LUPRON DEPOT, like other GnRH agonists, causes increases in serum levels of testosterone to approximately 50% above baseline during the first weeks of treatment. Isolated cases of ureteral obstruction and spinal cord compression have been observed, which may contribute to paralysis with or without fatal complications. Transient worsening of symptoms may develop. A small number of patients may experience a temporary increase in bone pain, which can be managed symptomatically.

Patients with metastatic vertebral lesions and/or with urinary tract obstruction should be closely observed during the first few weeks of therapy.

Hyperglycemia and Diabetes

Hyperglycemia and an increased risk of developing diabetes have been reported in men receiving GnRH agonists. Hyperglycemia may represent development of diabetes mellitus or worsening of glycemic control in patients with diabetes. Monitor blood glucose and/or glycosylated hemoglobin (HbA1c) periodically in patients receiving a GnRH agonist and manage with current practice for treatment of hyperglycemia or diabetes.

Cardiovascular Diseases

Increased risk of developing myocardial infarction, sudden cardiac death and stroke has been reported in association with use of GnRH agonists in men. The risk appears low based on the reported odds ratios, and should be evaluated carefully along with cardiovascular risk factors when determining a treatment for patients with prostate cancer. Patients receiving a GnRH agonist should be monitored for symptoms and signs suggestive of development of cardiovascular disease and be managed according to current clinical practice.

Effect on QT/QTc Interval

Long-term androgen deprivation therapy prolongs the QT interval. Physicians should consider whether the benefits of androgen deprivation therapy outweigh the potential risks in patients with congenital long QT syndrome, electrolyte abnormalities, or congestive heart failure and in patients taking class IA (e.g., quinidine, procainamide) or Class III (e.g., amiodarone, sotalol) antiarrhythmic medications.

Laboratory Tests

Response to LUPRON DEPOT 22.5 mg for 3-month administration, 30 mg for 4-month administration, and 45 mg for 6-month administration should be monitored by measuring serum levels of testosterone. In the majority of patients, testosterone levels increased above baseline, declining thereafter to castrate levels ( < 50 ng/dL) within four weeks. [see Clinical Studies and ADVERSE REACTIONS].

Nonclinical Toxicology

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 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.

Genotoxicity studies were conducted with leuprolide acetate using bacterial and mammalian systems. These studies provided no evidence of mutagenic effects or chromosomal aberrations.

Leuprolide may reduce male and female fertility. Administration of leuprolide acetate to male and female rats at dose of 0.024, 0.24, and 2.4 mg/kg as monthly depot formulation for up to 3 months (approximately as low as 1/30 of the human dose based on body surface area using an estimated daily dose in animals and humans) caused atrophy of the reproductive organs, and suppression of reproductive function. These changes were reversible upon cessation of treatment. Clinical and pharmacologic studies in adults ( ≥ 18 years) with leuprolide acetate and similar analogs have shown reversibility of fertility suppression when the drug is discontinued after continuous administration for periods of up to 24 weeks.

Clinical and pharmacologic studies in adults ( ≥ 18 years) with leuprolide acetate and similar analogs have shown reversibility of fertility suppression when the drug is discontinued after continuous administration for periods of up to 24 weeks.

Use In Specific Populations

Pregnancy

Pregnancy Category X [see CONTRAINDICATIONS].

LUPRON DEPOT is contraindicated in women who are or may become pregnant while receiving the drug. Expected hormonal changes that occur with LUPRON DEPOT treatment increase the risk for pregnancy loss and fetal harm when administered to a pregnant woman. 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.

Major fetal abnormalities were observed in rabbits after a single administration of the monthly formulation of LUPRON DEPOT on day 6 of pregnancy at doses of 0.00024, 0.0024, and 0.024 mg/kg (approximately 1/1600 to 1/16 the human dose based on body surface area using an estimated daily dose in animals and humans). Since a depot formulation was utilized in the study, a sustained exposure to leuprolide was expected throughout the period of organogenesis and to the end of gestation. Similar studies in rats did not demonstrate an increase in fetal malformations, however, there was increased fetal mortality and decreased fetal weights with the two higher doses of the monthly formulation of LUPRON DEPOT in rabbits and with the highest dose (0.024 mg/kg) in rats.

Nursing Mothers

LUPRON DEPOT is not indicated for women [see INDICATIONS AND USAGE]. It is not known whether leuprolide 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 LUPRON DEPOT, a decision should be made to discontinue nursing or discontinue the drug taking into account the importance of the drug to the mother.

Pediatric Use

See LUPRON DEPOT-PED® (leuprolide acetate for depot suspension) labeling for the safety and effectiveness in children with central precocious puberty.

Geriatric Use

In the clinical trials for LUPRON DEPOT in prostate cancer, the majority (approximately 80%) of the subjects studied were at least 65 years of age. Therefore, the labeling reflects the pharmacokinetics, efficacy and safety of LUPRON DEPOT in this population.

Last reviewed on RxList: 8/3/2012
This monograph has been modified to include the generic and brand name in many instances.

OVERDOSE

There is no experience of overdosage in clinical trials. In rats, a single subcutaneous dose of 100 mg/kg (approximately 4,000 times the estimated daily human dose based on body surface area), resulted in dyspnea, decreased activity, and excessive scratching. In early clinical trials with daily subcutaneous 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.

CONTRAINDICATIONS

Hypersensitivity

LUPRON DEPOT is contraindicated in individuals with known hypersensitivity to GnRH agonists or any of the excipients in LUPRON DEPOT. Reports of anaphylactic reactions to GnRH agonists have been reported in the medical literature.

Pregnancy

LUPRON DEPOT may cause fetal harm when administered to a pregnant woman. Expected hormonal changes that occur with LUPRON DEPOT treatment increase the risk for pregnancy loss and fetal harm when administered to a pregnant woman [see Use In Specific Populations]. LUPRON DEPOT 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 apprised of the potential hazard to the fetus.

Last reviewed on RxList: 8/3/2012
This monograph has been modified to include the generic and brand name in many instances.

CLINICAL PHARMACOLOGY

Mechanism of Action

Leuprolide acetate, a GnRH agonist, acts as an inhibitor of gonadotropin secretion. Animal studies indicate that following an initial stimulation, continuous administration of leuprolide acetate results in suppression of ovarian and testicular steroidogenesis. This effect was 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.

Pharmacodynamics

In humans, administration 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 premenopausal females). However, continuous administration of leuprolide acetate results in decreased levels of LH and FSH. In males, testosterone is reduced to castrate levels. In premenopausal females, estrogens are reduced to postmenopausal 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 more than five years.

Leuprolide acetate is not active when given orally.

Pharmacokinetics

Absorption

LUPRON DEPOT 22.5 mg for 3-Month Administration

Following a single injection of LUPRON DEPOT 22.5 mg for 3-month administration in patients, mean peak plasma leuprolide concentration of 48.9 ng/mL was observed at 4 hours and then declined to 0.67 ng/mL at 12 weeks. Leuprolide appeared to be released at a constant rate following the onset of steady-state levels during the third week after dosing, providing steady plasma concentrations through the 12-week dosing interval. However, intact leuprolide and an inactive major metabolite could not be distinguished by the assay which was employed in the study. Detectable levels of leuprolide were present at all measurement points in all patients. The initial burst, followed by the rapid decline to a steady-state level, was similar to the release pattern seen with the monthly formulation.

LUPRON DEPOT 30 mg for 4-Month Administration

Following a single injection of LUPRON DEPOT 30 mg for 4-month administration in sixteen orchiectomized prostate cancer patients, mean plasma leuprolide concentration of 59.3 ng/mL was observed at 4 hours and the mean concentration then declined to 0.30 ng/mL at 16 weeks. The mean plasma concentration of leuprolide from weeks 3.5 to 16 was 0.44 ± 0.20 ng/mL (range: 0.20-1.06). Leuprolide appeared to be released at a constant rate following the onset of steady-state levels during the fourth week after dosing, providing steady plasma concentrations throughout the 16-week dosing interval. However, intact leuprolide and an inactive major metabolite could not be distinguished by the assay which was employed in the study. The initial burst, followed by the rapid decline to a steady-state level, was similar to the release pattern seen with the other depot formulations.

LUPRON DEPOT 45 mg for 6-Month Administration

Following a single injection of LUPRON DEPOT 45 mg for 6-month administration in 26 prostate cancer patients, mean peak plasma leuprolide concentration of 6.7 ng/mL was observed at 2 hours and the mean concentration then declined to 0.07 ng/mL at 24 weeks. Leuprolide appeared to be released continuously following the onset of steady-state levels during the third week after dosing providing steady plasma concentrations through the 24-week dosing interval. The initial burst, followed by the rapid decline to a steady-state level, was similar to the release pattern seen with the other depot formulations. In this study, mean leuprolide plasma concentration-time profiles were similar after the first and second dose.

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.

Clinical Studies

LUPRON DEPOT 22.5 mg for 3-Month Administration

In clinical studies, serum testosterone was suppressed to castrate within 30 days in 87 of 92 (95%) patients and within an additional two weeks in three patients. Two patients did not suppress for 15 and 28 weeks, respectively. Suppression was maintained in all of these patients with the exception of transient minimal testosterone elevations in one of them, and in another an increase in serum testosterone to above the castrate range was recorded during the 12 hour observation period after a subsequent injection. This represents stimulation of gonadotropin secretion.

Figure 1: LUPRON DEPOT 22.5 mg for 3-Month Administration
Mean Serum Testosterone Concentrations

Mean Serum Testosterone Concentrations - Illustration

An 85% rate of “no progression” was achieved during the initial 24 weeks of treatment. A decrease from baseline in serum PSA of ≥ 90% was reported in 71% of the patients and a change to within the normal range ( ≤ 3.99 ng/mL) in 63% of the patients.

Periodic monitoring of serum testosterone and 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.

LUPRON DEPOT 30 mg for 4-Month Administration

In an open-label, noncomparative, multicenter clinical study of LUPRON DEPOT 30 mg for 4-month administration, 49 patients with stage D2 prostatic adenocarcinoma (with no prior treatment) were enrolled. The objectives were to determine whether a 30 mg depot formulation of leuprolide injected once every 16 weeks would reduce and maintain serum testosterone levels at castrate levels ( ≤ 50 ng/dL), and to assess the safety of the formulation. The study was divided into an initial 32-week treatment phase and a long-term treatment phase. Serum testosterone levels were determined biweekly or weekly during the first 32 weeks of treatment. Once the patient completed the initial 32-week treatment period, treatment continued at the investigator's discretion with serum testosterone levels being done every 4 months prior to the injection.

In the majority of patients, testosterone levels increased 50% or more above the baseline during the first week of treatment. Mean serum testosterone subsequently suppressed to castrate levels within 30 days of the first injection in 94% of patients and within 43 days in all 49 patients during the initial 32-week treatment period. The median dosing interval between injections was 112 days. One escape from suppression (two consecutive testosterone values greater than 50 ng/dL after castrate levels achieved) was noted at Week 16. In this patient, serum testosterone increased to above the castrate range following the second depot injection (Week 16) but returned to the castrate level by Week 18. No adverse reactions were associated with this rise in serum testosterone. A second patient had a rise in testosterone at Week 17, then returned to the castrate level by Week 18 and remained there through Week 32. In the long-term treatment phase two patients experienced testosterone elevations, both at Week 48. Testosterone for one patient returned to the castrate range at Week 52, and one patient discontinued the study at Week 48 due to disease progression.

Secondary efficacy endpoints evaluated in the study were the objective tumor response as assessed by clinical evaluations of tumor burden (complete response, partial response, objectively stable and progression) and evaluations of changes in prostatic involvement and prostate-specific antigen (PSA). These evaluations were performed at Weeks 16 and 32 of the treatment phase. The long-term treatment phase monitored PSA at each visit (every 16 weeks). The objective tumor response analysis showed “no progression” (i.e. complete or partial response, or stable disease) in 86% (37/43) of patients at Week 16, and in 77% (37/48) of patients at Week 32. Local disease improved or remained stable in all patients evaluated at Week 16 and/or 32. For patients with elevated baseline PSA, 50% (23/46) had a normal PSA (less than 4.0 ng/mL) at Week 16, and 51% (19/37) had a normal PSA at Week 32.

Periodic monitoring of serum testosterone and 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.

Using historical comparisons, the safety and efficacy of LUPRON DEPOT 30 mg for 4-month administration appear similar to the other LUPRON DEPOT formulations.

Figure 2: LUPRON DEPOT 30 mg for 4-Month Administration
Mean Serum Testosterone Concentrations

Mean Serum Testosterone Concentrations - Illustration

LUPRON DEPOT 45 mg for 6-Month Administration

An open-label, non-comparative, multicenter clinical study of LUPRON DEPOT 45 mg for 6-month administration enrolled 151 patients with prostate cancer. The study drug was administered as two intramuscular injections of LUPRON DEPOT 45 mg at 24 week intervals (139/151 received 2 injections), and patients were followed for a total of 48 weeks.

Among 148 patients who had testosterone value at Week 4, serum testosterone was suppressed to castrate levels ( < 50 ng/dL) from Week 4 through Week 48 in an estimated 93.4% (two-sided 95% CI: 89.2%, 97.6%) of patients. One patient failed to achieve testosterone suppression by Week 4, and eight patients had escapes from suppression (any testosterone value > 50 ng/dL after castrate levels were achieved). Mean testosterone levels increased to 608 ng/dL from a baseline of 435 ng/dL during the first week of treatment. By Week 4, the mean testosterone concentration had decreased to below castrate levels (16 ng/dL).

Periodic monitoring of serum testosterone levels is recommended, especially if the anticipated clinical or biochemical response to treatment has not been achieved. Testosterone determinations are dependent on assay methodology and it is advisable to be aware of the type and precision of the assay methodology to make appropriate clinical and therapeutic decisions.

Figure 3 below shows the mean testosterone concentration at various time points.

Figure 3: LUPRON DEPOT 45 mg for 6-Month Administration
Serum Testosterone Concentrations (Mean + SE)

Serum Testosterone Concentrations - Illustration

Last reviewed on RxList: 8/3/2012
This monograph has been modified to include the generic and brand name in many instances.

PATIENT INFORMATION

Patients should be informed that:

  • If they experience an allergic reaction to other drugs like LUPRON DEPOT, they should not use this drug.
  • The most common side effects associated with LUPRON DEPOT are hot flashes, pain (especially joint pain and back pain), injection site pain and fatigue.
  • LUPRON DEPOT may cause impotence.
  • The increase in testosterone that occurs during the first weeks of therapy can cause an increase in urinary symptoms or pain.
  • If they have metastatic cancer to the spine or urinary tract, they need close medical attention during the first weeks of therapy.
  • They should notify their doctor if they develop new or worsened symptoms after beginning LUPRON DEPOT treatment.

Last reviewed on RxList: 8/3/2012
This monograph has been modified to include the generic and brand name in many instances.

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PATIENT INFORMATION

Patients should be informed that:

  • If they experience an allergic reaction to other drugs like LUPRON DEPOT, they should not use this drug.
  • The most common side effects associated with LUPRON DEPOT are hot flashes, pain (especially joint pain and back pain), injection site pain and fatigue.
  • LUPRON DEPOT may cause impotence.
  • The increase in testosterone that occurs during the first weeks of therapy can cause an increase in urinary symptoms or pain.
  • If they have metastatic cancer to the spine or urinary tract, they need close medical attention during the first weeks of therapy.
  • They should notify their doctor if they develop new or worsened symptoms after beginning LUPRON DEPOT treatment.

Last reviewed on RxList: 8/3/2012
This monograph has been modified to include the generic and brand name in many instances.

Disclaimer

Lupron Depot Consumer

IMPORTANT: HOW TO USE THIS INFORMATION: This is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate for you. This information is not individual medical advice and does not substitute for the advice of your health care professional. Always ask your health care professional for complete information about this product and your specific health needs.

LEUPROLIDE 4 MONTH (30 MG) - INTRAMUSCULAR INJECTION

(LEW-pro-lide)

COMMON BRAND NAME(S): Lupron Depot

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. Talk to your doctor about the risks and benefits of treatment.

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. Leuprolide may also be used to stop early puberty in children.

HOW TO USE: This medication is given as an injection into a muscle (intramuscularly), usually once every 4 months by a health care professional or as directed by your doctor. This product slowly releases the medication into your blood over a 4-month period.

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.

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, mark your calendar to keep track of when to receive the next dose.

Disclaimer

Lupron Depot Consumer (continued)

SIDE EFFECTS: Hot flashes (flushing), increased sweating, night sweats, tiredness, swelling of the ankles/feet, increased urination at night, dizziness, or mild burning/pain/bruising at the injection site may occur. If any of these effects persist or worsen, tell your doctor or pharmacist promptly.

Infrequently, 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.

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 level of testosterone will actually increase before it decreases. This is a normal response by your body to this drug. This 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: new/worsening bone pain, easily broken bones, increased thirst/urination, mental/mood changes (such as depression, thoughts of suicide, mood swings, aggression in children).

Get medical help right away if any of these rare but serious side effects occur: chest/jaw/left arm pain, irregular heartbeat, weakness on one side of the body, slurred speech.

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 (especially of the face/tongue/throat), 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.

In the US -

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

In Canada - Call your doctor for medical advice about side effects. You may report side effects to Health Canada at 1-866-234-2345.

Read the Lupron Depot (leuprolide acetate for depot suspension) Side Effects Center for a complete guide to possible side effects »

PRECAUTIONS: Before using leuprolide, tell your doctor or pharmacist if you are allergic to it; or if you have any other allergies. This product may contain inactive ingredients, which can cause allergic reactions or other problems. Talk to your pharmacist for more details.

Before using this medication, tell your doctor or pharmacist your medical history, especially of: diabetes, heart disease (such as heart attack), stroke, high cholesterol, family history of sudden cardiac death.

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. Do not drive, use machinery, or do any activity that requires alertness until you are sure you can perform such activities safely. 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 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.

Disclaimer

Lupron Depot Consumer (continued)

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., blood testosterone level, PSA blood test, blood glucose) 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 do miss a dose, contact your doctor promptly to establish a new schedule.

STORAGE: Store at room temperature at 77 degrees F (25 degrees C) away from moisture. Brief storage between 59-86 degrees F (15-30 degrees C) is permitted. Once mixed, use the medication immediately. 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 February 2012. Copyright(c) 2012 First Databank, Inc.

Lupron Depot Patient Information Including Side Effects

Brand Names: Eligard, Lupron, Lupron Depot, Lupron Depot-Gyn, Lupron Depot-Ped

Generic Name: leuprolide (Pronunciation: LOO proe lide)

What is leuprolide (Lupron Depot)?

Leuprolide is a man-made form of a hormone that regulates many processes in the body. 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. Leuprolide treats only the symptoms of prostate cancer and does not treat the cancer itself. Use any other medications your doctor has prescribed to best treat your condition.

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.

What are the possible side effects of leuprolide (Lupron Depot)?

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficulty breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have a serious side effect such as:

  • bone pain, loss of movement in any part of your body;
  • swelling, rapid weight gain;
  • pain, burning, stinging, bruising, or redness where the medication was injected;
  • feeling like you might pass out;
  • painful or difficult urination;
  • urinating more often than usual;
  • high blood sugar (increased thirst, increased urination, hunger, dry mouth, fruity breath odor, drowsiness, dry skin, blurred vision, weight loss);
  • sudden numbness or weakness (especially on one side of the body), problems with speech or balance;
  • sudden headache with vision problems, vomiting, confusion, slow heart rate, weak pulse, fainting, or slow breathing; or
  • chest pain or heavy feeling, pain spreading to the arm or shoulder, nausea, sweating, general ill feeling.

Rare but serious side effects may include:

  • pain or unusual sensations in your back;
  • numbness, weakness, or tingly feeling in your legs or feet;
  • muscle weakness or loss of use; and
  • loss of bowel or bladder control.

Less serious side effects may include:

  • acne, increased growth of facial hair;
  • breakthrough bleeding in a female child during the first 2 months of leuprolide treatment;
  • dizziness, weakness, tired feeling;
  • hot flashes, night sweats, chills, clammy skin;
  • nausea, diarrhea, constipation, stomach pain;
  • skin redness, itching, or scaling;
  • joint or muscle pain;
  • vaginal itching or discharge
  • breast swelling or tenderness;
  • testicle pain;
  • impotence, loss of interest in sex;
  • depression, sleep problems (insomnia), memory problems; or
  • redness, burning, stinging, or pain where the shot was given.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Read the Lupron Depot (leuprolide acetate for depot suspension) Side Effects Center for a complete guide to possible side effects »

What is the most important information I should know about leuprolide (Lupron Depot)?

You should not breast-feed while you are using leuprolide.

You should not use this medication if you are allergic to leuprolide or similar medications such as buserelin (Suprefact, Suprecor), goserelin (Zoladex), histrelin (Supprelin), or nafarelin (Synarel).

You should not use leuprolide if you have abnormal vaginal bleeding that has not been diagnosed by a doctor.

Before using leuprolide, tell your doctor if you have epilepsy, asthma, migraines, heart or kidney disease, a history of depression, osteoporosis, bone cancer affecting your spine, blood in your urine, or if you are unable to urinate.

Tell your doctor if you have a personal or family history of osteoporosis, or if you have any risk factors for bone loss such as smoking, alcohol use, or taking steroid or seizure medications long term. Long-term use of this medication may decrease bone density, possibly leading to osteoporosis.

Certain brands or strengths of leuprolide are used to treat only men and should not be used in women or children. Always check your medication to make sure you have received the correct brand and strength prescribed by your doctor.

Lupron Depot Patient Information including How Should I Take

What should I discuss with my healthcare provider before using leuprolide (Lupron Depot)?

Certain brands or strengths of leuprolide are used to treat only men and should not be used in women or children. Always check your medication to make sure you have received the correct brand and strength prescribed by your doctor. Ask the pharmacist if you have any questions about the medicine you receive at the pharmacy.

You should not use this medication if you are allergic to leuprolide or similar medications such as buserelin (Suprefact, Suprecor), goserelin (Zoladex), histrelin (Supprelin), nafarelin (Synarel), or if you have:

  • abnormal vaginal bleeding that has not been diagnosed by a doctor; or
  • if you are pregnant or breast-feeding.

Do not breast-feed a baby while using leuprolide.

To make sure you can safely use leuprolide, tell your doctor if you have any of these other conditions:

  • a personal or family history of osteoporosis;
  • risk factors for bone loss such as smoking, alcohol use, or taking steroid or seizure medications long term;
  • diabetes, heart disease, high blood pressure, recent weight gain, high cholesterol (especially in men);
  • epilepsy;
  • asthma;
  • migraines;
  • kidney disease;
  • a history of depression;
  • bone cancer affecting your spine;
  • blood in your urine; or
  • if you are unable to urinate.

FDA pregnancy category X. This medication can cause birth defects. Do not use leuprolide if you are pregnant. Tell your doctor right away if you become pregnant during treatment.

Leuprolide usually causes women to stop ovulating or having menstrual periods. However, you may still be able to get pregnant. Use an effective barrier form of birth control (such as a condom or diaphragm with spermicide gel or inserts). Hormonal forms of contraception (such as birth control pills, injections, implants, skin patches, and vaginal rings) may not be effective in preventing pregnancy while you are using leuprolide.

Because leuprolide is expected to cause your menstrual periods to stop, contact your doctor if your periods continue while you are being treated with this medication.

Long-term use of this medication may decrease bone density, possibly leading to osteoporosis. Talk with your doctor about your possible risk for osteoporosis. You may need to receive a bone scan if you ever need to be re-treated with leuprolide in the future.

How should I use leuprolide (Lupron Depot)?

Leuprolide is injected under the skin or into a muscle. You may be shown how to use injections at home. Do not self-inject this medicine if you do not fully understand how to give the injection and properly dispose of used needles and syringes.

This medication comes with patient instructions for safe and effective use. Follow these directions carefully. Ask your doctor or pharmacist if you have any questions.

Leuprolide may be given once every month or once every 3 to 6 months. How often you receive this medication will depend on the condition being treated. Follow your doctor's instructions.

Because different brands or strengths of leuprolide are used to treat different conditions, it is very important that you receive exactly the brand and strength your doctor has prescribed. If you self-inject this medication at home, always check your medication to make sure you have received the correct brand and type prescribed by your doctor.

Your symptoms may become temporarily worse as your hormones adjust when you first start using this medication. For best results, keep using the medication as instructed by your doctor. Your condition should eventually improve with continued use of leuprolide.

To be sure this medication is helping your condition, your blood may need to be tested often. This will help your doctor determine how long to treat you with leuprolide. You may still need blood tests for up to 3 months after you stop using leuprolide to check your hormone levels and pituitary gland function. Do not miss any scheduled appointments.

Store Lupron in the original carton at room temperature, away from moisture and heat.

Store Eligard in the refrigerator. Do not freeze. You may take the medicine out and allow it to reach room temperature before mixing and injecting your dose. After the dose is mixed, you must use the injection within 30 minutes.

Use a disposable needle only once. Throw away used needles in a puncture-proof container (ask your pharmacist where you can get one and how to dispose of it). Keep this container out of the reach of children and pets.

Lupron Depot Patient Information including If I Miss a Dose

What happens if I miss a dose (Lupron Depot)?

Call your doctor for instructions if you miss a dose.

Women who miss more than one leuprolide dose may have breakthrough bleeding. Children who miss more than one dose may have a return of pubertal symptoms such as breast development, growth in the testicles, or menstrual periods.

What happens if I overdose (Lupron Depot)?

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

Overdose symptoms may include weakness, or irritation where the leuprolide shot was given.

What should I avoid while using leuprolide (Lupron Depot)?

Follow your doctor's instructions about any restrictions on food, beverages, or activity.

What other drugs will affect leuprolide (Lupron Depot)?

There may be other drugs that can interact with leuprolide. Tell your doctor about all medications you use. This includes prescription, over-the-counter, vitamin, and herbal products. Do not start a new medication without telling your doctor.

Where can I get more information?

Your pharmacist can provide more information about leuprolide.


Remember, keep this and all other medicines out of the reach of children, never share your medicines with others, and use this medication only for the indication prescribed.

Every effort has been made to ensure that the information provided by Cerner Multum, Inc. ('Multum') is accurate, up-to-date, and complete, but no guarantee is made to that effect. Drug information contained herein may be time sensitive. Multum information has been compiled for use by healthcare practitioners and consumers in the United States and therefore Multum does not warrant that uses outside of the United States are appropriate, unless specifically indicated otherwise. Multum's drug information does not endorse drugs, diagnose patients or recommend therapy. Multum's drug information is an informational resource designed to assist licensed healthcare practitioners in caring for their patients and/or to serve consumers viewing this service as a supplement to, and not a substitute for, the expertise, skill, knowledge and judgment of healthcare practitioners. The absence of a warning for a given drug or drug combination in no way should be construed to indicate that the drug or drug combination is safe, effective or appropriate for any given patient. Multum does not assume any responsibility for any aspect of healthcare administered with the aid of information Multum provides. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the drugs you are taking, check with your doctor, nurse or pharmacist.

Copyright 1996-2012 Cerner Multum, Inc. Version: 14.01. Revision date: 9/13/2011.

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