Lupron Depot

Lupron Depot (leuprolide acetate for depot suspension) is a man-made form of gonadotropin-releasing hormone (GnRH) used in men to treat the symptoms of prostate cancer. Lupron Depot is used in women to treat symptoms of endometriosis (overgrowth of uterine lining outside of the uterus) or uterine fibroids, and is also used to treat precocious (early-onset) puberty in both male and female children. Common side effects of Lupron Depot include:

• hot flashes (flushing)
• increased sweating
• night sweats
• chills
• clammy skin
• tiredness
• swelling of the ankles/feet
• increased urination at night
• mental/mood changes (e.g., depression, mood swings)
• dizziness
• injection site reactions (burning, redness, stinging, pain, bruising, swelling, abscess)
• acne
• increased growth of facial hair
• breakthrough bleeding in a female child during the first 2 months of Lupron Depot treatment
• weakness
• nausea
• diarrhea
• constipation
• stomach pain
• skin redness/itching/scaling
• joint or muscle pain
• vaginal itching or discharge
• breast swelling or tenderness
• testicle pain
• impotence
• loss of interest in sex
• sleep problems (insomnia)
• rash (including a painful rash with fever)
• memory problems
• blisters/sores
• facial swelling
• vaginitis
• weight gain
• headache

The recommended dose of Lupron Depot 22.5 mg for 3-month administration is one injection every 12 weeks. The recommended dose of Lupron Depot 30 mg for 4-month administration is one injection every 16 weeks. It is administered under physician supervision. Other drugs may interact with Lupron Depot. Tell your doctor all medications and supplements you use. Lupron Depot must not be used during pregnancy. It may harm a fetus. If you become pregnant or think you may be pregnant, inform your doctor. Consult your doctor to discuss birth control. Non-hormonal birth control methods are recommended. It is unknown if this drug passes into breast milk. Because the effects on a nursing infant are unknown, breastfeeding is not recommended.

Our Lupron Depot (leuprolide acetate for depot suspension) Side Effects Drug Center provides a comprehensive view of available drug information on the potential side effects when taking this medication.

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.

Get emergency medical help if you have signs of an allergic reaction (hives, difficult breathing, swelling in your face or throat) or a severe skin reaction (fever, sore throat, burning in your eyes, skin pain, red or purple skin rash that spreads and causes blistering and peeling).

Call your doctor at once if you have:

• bone pain, loss of movement in any part of your body;
• swelling, rapid weight gain;
• a seizure;
• unusual changes in mood or behavior (crying spells, anger, feeling irritable);
• sudden chest pain or discomfort, wheezing, dry cough or hack;
• painful or difficult urination; or
• high blood sugar--increased thirst, increased urination, hunger, dry mouth, fruity breath odor.

Rare but serious side effects may occur. Call your doctor if you have:

• pain or unusual sensations in your back, numbness, weakness, or tingly feeling in your legs or feet;
• muscle weakness or loss of use, loss of bowel or bladder control;
• heart attack symptoms--chest pain or pressure, pain spreading to your jaw or shoulder, nausea, sweating; or
• signs of a stroke--sudden numbness or weakness (especially on one side of the body), sudden severe headache, slurred speech.

Common side effects may include:

• hot flashes, sweating, acne, rash, itching, scaly skin;
• mood changes;
• headache, general pain;
• vaginal swelling, itching, or discharge;
• breakthrough bleeding;
• weight gain;
• decreased testicle size; or
• redness, pain, swelling, or oozing 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 entire detailed patient monograph for Lupron Depot (Leuprolide Acetate for Depot Suspension)

SIDE EFFECTS

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

LUPRON DEPOT 7.5 mg For 1-Month Administration

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.

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 or hematuria which, if aggravated, may lead to neurological problems such as temporary weakness and/or paresthesia of the lower limbs or worsening of urinary symptoms [see WARNINGS AND PRECAUTIONS].

In a clinical trial of LUPRON DEPOT 7.5 mg for 1-month administration, the following adverse reactions were reported in 5% or more of the patients during the initial 24-week treatment period.

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

LUPRON DEPOT 7.5 mg for 1-Month Administration (N=56)
	N	(%)
Body As A Whole
General pain	13	(23.2)
Infection	3	(5.4)
Cardiovascular System
Hot flashes/sweats*	32	(57.1)
Digestive System
GI disorders	8	(14.3)
Metabolic and Nutritional Disorders
Edema	8	(14.3)
Nervous System
Libido decreased*	3	(5.4)
Respiratory System
Respiratory disorder	6	(10.7)
Urogenital System
Urinary disorder	7	(12.5)
Impotence*	3	(5.4)
Testicular atrophy*	3	(5.4)
* Due to the expected physiologic effect of decreased testosterone levels.

In this same study, the following adverse reactions were reported in less than 5% of the patients on LUPRON DEPOT 7.5 mg for 1-month administration.

Body As A Whole - Asthenia, Cellulitis, Fever, Headache, Injection site reaction, Neoplasm

Cardiovascular System - Angina, Congestive heart failure

Digestive System - Anorexia, Dysphagia, Eructation, Peptic ulcer

Hemic and Lymphatic System - Ecchymosis

Musculoskeletal System - Myalgia

Nervous System - Agitation, Insomnia/sleep disorders, Neuromuscular disorders

Respiratory System - Emphysema, Hemoptysis, Lung edema, Sputum increased

Skin and Appendages - Hair disorder, Skin reaction

Urogenital System - Balanitis, Breast enlargement, Urinary tract infection

Laboratory Abnormalities

Abnormalities of certain parameters were observed, but their relationship to drug treatment are difficult to assess in this population. The following were recorded in ≥ 5% of patients at final visit: Decreased albumin, decreased hemoglobin/hematocrit, decreased prostatic acid phosphatase, decreased total protein, decreased urine specific gravity, hyperglycemia, hyperuricemia, increased BUN, increased creatinine, increased liver function tests (AST, LDH), increased phosphorus, increased platelets, increased prostatic acid phosphatase, increased total cholesterol, increased urine specific gravity, leukopenia.

LUPRON DEPOT 22.5 mg For 3-Month Administration

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 3: 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	(16.0)
Musculoskeletal System
Joint Disorders	11	(117)
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

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

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.

Table 4: Adverse Reactions Reported in ≥ 5% of Patients

LUPRON DEPOT 30 mg for 4-Month Administration
Body System/Events	Non orchiectomized Study 013		Orchiectomized 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

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

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 5 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 5: 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
F atigue/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	2.0
Musculoskeletal Pain/ Myalgia	12	7.9	3	2.0
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	2.0
Rash	9	6.0	3	2.0
Dysuria	9	6.0	1	0.7
Urinary Tract Infection/Cystitis	9	6.0	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	2.0
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, non-Hodgkin'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 Abnormalities

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

The following adverse reactions have been identified during post-approval use of LUPRON DEPOT. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.

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

Hepato-biliary disorder - Serious drug-induced liver injury

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 entire FDA prescribing information for Lupron Depot (Leuprolide Acetate for Depot Suspension)

Read the Lupron Depot User Reviews »

© Lupron Depot Patient Information is supplied by Cerner Multum, Inc. and Lupron Depot Consumer information is supplied by First Databank, Inc., used under license and subject to their respective copyrights.