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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
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 As A Whole|
|Injection Site Reaction||13||(13.8)|
|Central/Peripheral Nervous System|
|Skin and Appendages|
|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
Metabolic and Nutritional Disorders -Dehydration, Edema
Central/Peripheral Nervous System -Anxiety, Delusions, Depression, Hypesthesia, Libido decreased*, Nervousness, Paresthesia
* Physiologic effect of decreased testosterone.
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 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|
|Body As a Whole|
|Injection Site Reaction||4||(8.2)||9||(37.5)|
|Metabolic and Nutritional Disorders|
|Skin and Appendages|
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.
Cardiovascular System -Atrial fibrillation, Deep thrombophlebitis, Hypertension
Hemic and Lymphatic System -Lymphadenopathy
Metabolic and Nutritional Disorders -Healing abnormal, Hypoxia, Weight loss
Musculoskeletal System -Leg cramps, Pathological fracture, Ptosis
Skin and Appendages -Herpes zoster, Melanosis
* Physiologic effect of decreased testosterone.
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 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||(%)|
|Injection Site Pain/Discomfort||29||19.2||16||10.6|
|Upper Respiratory Tract Infection/Influenza-like Illness1||32||21.2||0||0|
|Musculoskeletal Pain/ Myalgia||12||7.9||3||2|
|Second Primary Neoplasm2||11||7.3||0||0|
|Urinary Tract Infection/Cystitis||9||6||0||0|
|Dyspnea/Dyspnea on Exertion||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
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.
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.
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.
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.
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
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.
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.
Read the Lupron Depot Drug Interactions Center for a complete guide to possible interactions
Last reviewed on RxList: 8/3/2012
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