LUTRATE DEPOT
Generic: LEUPROLIDE ACETATE
Basic Information
Manufacturer
Avyxa Pharma, LLC
Product Type
HUMAN PRESCRIPTION DRUG
Route of Administration
FDA Set ID
3a6d1373-17d9-4289-b62f-d299ffe55831
Indications & Usage
1 INDICATIONS AND USAGE LUTRATE DEPOT 22.5 mg for 3-month administration (leuprolide acetate) is indicated for treatment of advanced prostate cancer.
LUTRATE DEPOT is a gonadotropin-releasing hormone (GnRH) agonist indicated for: Treatment of advanced prostate cancer.
( 1 )
LUTRATE DEPOT is a gonadotropin-releasing hormone (GnRH) agonist indicated for: Treatment of advanced prostate cancer.
( 1 )
Adverse Reactions
6 ADVERSE REACTIONS The following is discussed in more detail in other sections of the labeling: Tumor Flare [see Warnings and Precautions (5.1) ] Metabolic Syndrome [ see Warnings and Precautions (5.2) ] Cardiovascular Disease [see Warnings and Precautions (5.3) ] Effect on QT/QTc Interval [ see Warnings and Precautions (5 .4) ] Convulsions [see Warnings and Precautions (5.5) ] Severe Cutaneous Adverse Reactions [see Warnings and Precautions (5.6) ] Most common adverse reactions (incidence > 10%) are hot flushes, upper respiratory infection, fatigue, diarrhea, pollakiuria, arthralgia, and injection site pain ( 6 ) .
As with other GnRH agonist, other adverse reactions, including decreased bone density and rare cases of pituitary apoplexy may occur.
( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Avyxa Pharma, LLC at 1-888-520-0954 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1 Clinical Trials Experience 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.
LUTRATE DEPOT 22.5 mg for 3-Month Administration In a clinical trial of LUTRATE DEPOT 22.5 mg for 3-month administration, patients were treated for 24 weeks with 157/163 receiving two injections.
The table includes adverse reactions were reported in 5% or more of the patients during the treatment period as well as the incidence of these adverse reaction that were considered, by the treating physician, to be at least possibly related to LUTRATE DEPOT.
Grade 3-4 adverse reactions reported as treatment-emergent in 13% of patients and treatment-related 4% of patients.
CTCAE v.3 1 Includes cold sweat, flushing, hot flush, hyperhidrosis, and night sweats 2 Includes influenza, influenza-like illness, nasal congestion, nasopharyngitis, rhinorrhea, upper respiratory tract infection and congestion Table 2.
Adverse Reactions Reported in ≥ 5% of Patients LUTRATE DEPOT 22.5 mg for 3-Month Administration N = 163 (%) Grade 1-4 Treatment-Emergent Treatment-Related Hot Flush/Flushing 1 128 (79) 127 (78) Upper Respiratory Infection 2 28 (17) 0 Fatigue/Asthenia 24 (15) 22 (13) Diarrhea 21 (13) 2 (1) Pollakiuria 20 (12) 3 (2) Arthralgia/Arthritis 18 (11) 2 (1) Injection Site Pain/Discomfort 18 (11) 15 (9) Constipation 15 (9) 1 (0.6) Extremity Pain 14 (9) 0 Nausea 14 (9) 4 (2) Nocturia 14 (9) 3 (2) Abdominal Pain/Discomfort 13 (8) 1 (0.6) Urinary Tract Pain 13 (8) 2 (1) Dizziness 12 (7) 2 (1) Headache/Sinus Headache 12 (7) 1 (0.6) Urinary Tract Infection 12 (7) 0 Bone Pain 11 (7) 4 (2) Back Pain 10 (6) 1 (0.6) Hypertension/Blood Pressure Increased 10 (6) 0 Pruritus/Generalized Pruritus 9 (6) 3 (2) In the same study, erectile dysfunction and testicular atrophy were reported in patients on LUTRATE DEPOT 22.5 mg.
Laboratory abnormalities During the treatment period, at least a one grade change in laboratory values was seen (>10%) in the following: anemia, increased triglyceride, hyperglycemia, increased cholesterol, increased creatine kinase, leukopenia, increased AST, increased creatinine, and increased ALT.
6.2 Post-marketing Experience The following adverse reactions have been identified during post approval use of gonadotropin-releasing hormone agonists.
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.
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 LUTRATE DEPOT.
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.
Pituitary apoplexy: During postmarketing 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.
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 acetate-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.
Immune Disorders: Anaphylaxis Psychiatric Disorders: Depression Cardiovascular System - hypotension, myocardial infarction, pulmonary embolism Respiratory, Thoracic and Mediastinal disorder - Pneumonitis, interstitial lung disease Hepato-biliary disorder - serious drug-induced liver injury, non-alcoholic fatty liver disease Skin reactions – rash, urticaria, photosensitivity, erythema multiforme, bullous dermatitis, exfoliative dermatitis, DRESS, SJS/TEN, and AGEP Blood and Lymphatic System - decreased WBC Central/Peripheral Nervous System - convulsion, peripheral neuropathy, spinal fracture/paralysis Endocrine System - diabetes mellitus Musculoskeletal System - tenosynovitis-like symptoms Urogenital System - prostate pain
As with other GnRH agonist, other adverse reactions, including decreased bone density and rare cases of pituitary apoplexy may occur.
( 6 ) To report SUSPECTED ADVERSE REACTIONS, contact Avyxa Pharma, LLC at 1-888-520-0954 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
6.1 Clinical Trials Experience 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.
LUTRATE DEPOT 22.5 mg for 3-Month Administration In a clinical trial of LUTRATE DEPOT 22.5 mg for 3-month administration, patients were treated for 24 weeks with 157/163 receiving two injections.
The table includes adverse reactions were reported in 5% or more of the patients during the treatment period as well as the incidence of these adverse reaction that were considered, by the treating physician, to be at least possibly related to LUTRATE DEPOT.
Grade 3-4 adverse reactions reported as treatment-emergent in 13% of patients and treatment-related 4% of patients.
CTCAE v.3 1 Includes cold sweat, flushing, hot flush, hyperhidrosis, and night sweats 2 Includes influenza, influenza-like illness, nasal congestion, nasopharyngitis, rhinorrhea, upper respiratory tract infection and congestion Table 2.
Adverse Reactions Reported in ≥ 5% of Patients LUTRATE DEPOT 22.5 mg for 3-Month Administration N = 163 (%) Grade 1-4 Treatment-Emergent Treatment-Related Hot Flush/Flushing 1 128 (79) 127 (78) Upper Respiratory Infection 2 28 (17) 0 Fatigue/Asthenia 24 (15) 22 (13) Diarrhea 21 (13) 2 (1) Pollakiuria 20 (12) 3 (2) Arthralgia/Arthritis 18 (11) 2 (1) Injection Site Pain/Discomfort 18 (11) 15 (9) Constipation 15 (9) 1 (0.6) Extremity Pain 14 (9) 0 Nausea 14 (9) 4 (2) Nocturia 14 (9) 3 (2) Abdominal Pain/Discomfort 13 (8) 1 (0.6) Urinary Tract Pain 13 (8) 2 (1) Dizziness 12 (7) 2 (1) Headache/Sinus Headache 12 (7) 1 (0.6) Urinary Tract Infection 12 (7) 0 Bone Pain 11 (7) 4 (2) Back Pain 10 (6) 1 (0.6) Hypertension/Blood Pressure Increased 10 (6) 0 Pruritus/Generalized Pruritus 9 (6) 3 (2) In the same study, erectile dysfunction and testicular atrophy were reported in patients on LUTRATE DEPOT 22.5 mg.
Laboratory abnormalities During the treatment period, at least a one grade change in laboratory values was seen (>10%) in the following: anemia, increased triglyceride, hyperglycemia, increased cholesterol, increased creatine kinase, leukopenia, increased AST, increased creatinine, and increased ALT.
6.2 Post-marketing Experience The following adverse reactions have been identified during post approval use of gonadotropin-releasing hormone agonists.
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.
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 LUTRATE DEPOT.
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.
Pituitary apoplexy: During postmarketing 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.
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 acetate-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.
Immune Disorders: Anaphylaxis Psychiatric Disorders: Depression Cardiovascular System - hypotension, myocardial infarction, pulmonary embolism Respiratory, Thoracic and Mediastinal disorder - Pneumonitis, interstitial lung disease Hepato-biliary disorder - serious drug-induced liver injury, non-alcoholic fatty liver disease Skin reactions – rash, urticaria, photosensitivity, erythema multiforme, bullous dermatitis, exfoliative dermatitis, DRESS, SJS/TEN, and AGEP Blood and Lymphatic System - decreased WBC Central/Peripheral Nervous System - convulsion, peripheral neuropathy, spinal fracture/paralysis Endocrine System - diabetes mellitus Musculoskeletal System - tenosynovitis-like symptoms Urogenital System - prostate pain