FDA label 768af325-a1bb-4692-97ce-4853feb356a8

5 WARNINGS AND PRECAUTIONS Tumor Flare: Transient worsening of bone pain, uretral obstruction, spinal cord compression, or the occurrence of additional signs and symptoms of prostate cancer may develop during the first few weeks of treatment. Monitor patients closely and manage symptoms. ( 5.1 ) Hyperglycemia and Diabetes: Hyperglycemia and an increased risk of developing diabetes have been reported in men receiving GnRH agonists. Monitor blood glucose level and manage according to current clinical practice. ( 5.2 ) Cardiovascular Diseases: Increased risk of myocardial infarction, sudden cardiac death, and stroke has been reported in men receiving GnRH agonists. Monitor for cardiovascular disease and manage according to current clinical practice. ( 5.3 ) QT/QTc Prolongation: Androgen deprivation therapy may prolong the QT interval. Consider periodic monitoring of electrocardiograms and electrolytes. ( 5.4 ) Convulsions: Manage convulsions according to the current clinical practice. ( 5.5 ) Embryo-Fetal Toxicity: CAMCEVI may cause fetal harm. ( 5.7 , 8.1 ) 5.1 Tumor Flare CAMCEVI, like other GnRH agonists, causes a transient increase in serum levels of testosterone during the first week of treatment, declining thereafter to baseline levels or below by the end of the second week of treatment. Transient worsening of symptoms, or the occurrence of additional signs and symptoms of prostate cancer, may develop during the first few weeks of CAMCEVI treatment. Patients treated with CAMCEVI may experience a temporary increase in bone pain, which can be managed symptomatically. As with other GnRH agonists, cases of ureteral obstruction and spinal cord compression have been observed, which may contribute to paralysis with or without fatal complications. Patients with metastatic vertebral lesions and/or with urinary tract obstruction should be closely observed during the first few weeks of therapy. 5.2 Hyperglycemia and Diabetes Hyperglycemia and an increased risk of developing diabetes have been reported in men receiving GnRH agonists. Hyperglycemia may represent the 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. 5.3 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. 5.4 QT/QTc Prolongation Androgen deprivation therapy may prolong the QT/QTc interval. Providers should consider whether the benefits of androgen deprivation therapy outweigh the potential risks in patients with congenital long QT syndrome, congestive heart failure, frequent electrolyte abnormalities, and in patients taking drugs known to prolong the QT interval. Electrolyte abnormalities should be corrected. Consider periodic monitoring of electrocardiograms and electrolytes. 5.5 Convulsions Convulsions have been reported in patients receiving GnRH agonists, like CAMCEVI [see Adverse Reactions (6.2) ]. Manage patients receiving a GnRH agonist who experience convulsions according to current clinical practice. 5.6 Laboratory Tests Monitor serum levels of testosterone following injection of CAMCEVI. In the majority of patients treated with CAMCEVI, testosterone levels increased above baseline during the first week, and then declined thereafter to castration levels (<50 ng/dL) within 4 weeks [see Clinical Studies (14) and Adverse Reactions (6) ]. 5.7 Embryo-Fetal Toxicity Based on findings in animal studies and mechanism of action, CAMCEVI can cause fetal harm when administered to a pregnant woman. In animal developmental and reproductive toxicology studies, administration of a monthly formulation of leuprolide on day 6 of pregnancy (sustained exposure was expected throughout the period of organogenesis) caused adverse embryo-fetal toxicity in animals at doses less than the human dose based on body surface area using an estimated daily dose. Advise pregnant patients and females of reproductive potential of the potential risk to the fetus [see Use in Specific Population (8.1) , Clinical Pharmacology (12.1) ] .

6 ADVERSE REACTIONS The following adverse reactions are discussed in greater detail in other sections of the labeling: • Tumor Flare [see Warnings and Precautions (5.1) ] • Hyperglycemia and Diabetes [see Warnings and Precautions (5.2) ] • Cardiovascular Diseases [see Warnings and Precautions (5.3) ] • QT/QTc Prolongation [see Warnings and Precautions (5.4) ] • Convulsions [see Warnings and Precautions (5.5) ] The most common ( > 10%) adverse reactions were hot flush, hypertension, injection site reactions, upper respiratory tract infections, musculoskeletal pain, fatigue, and pain in extremity. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Foresee Pharmaceuticals at 1-866-941-7875 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch 6.1 Clinical Trial 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. In an open-label, non-comparative clinical trial (FP01C-13-001), patients with advanced prostate cancer received CAMCEVI administered subcutaneously at a dose of 42 mg on Day 0 and Day 168. Of 137 patients enrolled, 93% received both doses of CAMCEVI. Serious adverse reactions occurred in 15% of patients who received CAMCEVI, including 1% of patients who experienced subdural hematoma. Fatal adverse reactions occurred in 2% of patients, including cerebrovascular accident (0.7%) and pulmonary embolism (0.7%). The most common adverse reactions ( > 10%) occurring during a median follow-up duration of 336 days were hot flush, hypertension, injection site reactions, upper respiratory tract infections, musculoskeletal pain, fatigue, and pain in extremity. Table 1 summarizes the adverse reactions in FP01C-13-001. Table 1. Adverse Reactions Occurring in ≥5% of Patients - FP01C-13-001 Adverse Reaction N = 137 All Grades (%) Grade 3-4 (%) Vascular disorders Hot flush includes hot flush and flushing 50 0 Hypertension includes hypertension, essential hypertension, and blood pressure increased 15 0 General disorders and administration site conditions Injection site reactions includes injection site pain, injection site erythema, injection site hemorrhage, injection site nodule, injection site paraesthesia, injection site pruritus, and injection site warmth 11 0 Fatigue includes fatigue and asthenia 10 0 Infections and infestations Upper respiratory tract infection includes upper respiratory tract infection, sinusitis, and nasopharyngitis 11 0 Musculoskeletal and connective tissue disorders Musculoskeletal pain includes musculoskeletal pain, back pain, and bone pain 11 0 Pain in extremity 10 0 Arthralgia 7 0 Renal and urinary disorders Micturition urgency includes micturition urgency and dysuria 6 0 Nocturia 6 0 Nervous system disorders Dizziness includes dizziness, dizziness postural, vertigo, and vertigo positional. 5 0.7 6.2 Postmarketing Experience The following adverse reactions have been identified during post approval use of leuprolide. 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. Allergic Conditions: anaphylactoid or asthmatic process, rash, urticaria, and photosensitivity reactions Cardiovascular System: hypotension, myocardial infarction, pulmonary embolism Central/Peripheral Nervous System: convulsion, peripheral neuropathy, spinal fracture/paralysis Endocrine System: pituitary apoplexy, diabetes Hepato-biliary disorder: drug-induced liver injury Hematologic: white blood cells Psychiatric: mood swings, including depression, suicidal ideation and attempt Respiratory, thoracic and mediastinal disorder: interstitial lung disease Musculoskeletal System: decreased bone density, tenosynovitis-like symptoms, fibromyalgia Skin and Subcutaneous: injection site reactions Urogenital System: prostate pain

<table width="100%"><caption> Table 1. Adverse Reactions Occurring in &#x2265;5% of Patients - FP01C-13-001</caption><tbody><tr><td rowspan="2" align="center"><content styleCode="underline"><content styleCode="bold"> Adverse Reaction</content></content></td><td colspan="2" align="center"><content styleCode="underline"><content styleCode="bold"> N = 137 </content></content></td></tr><tr><td align="center"><content styleCode="underline"><content styleCode="bold"> All Grades</content></content> <content styleCode="underline"><content styleCode="bold">(%)</content></content></td><td align="center"><content styleCode="underline"><content styleCode="bold"> Grade 3-4</content></content> <content styleCode="underline"><content styleCode="bold">(%)</content></content></td></tr><tr><td colspan="3"> Vascular disorders </td></tr><tr><td> Hot flush<footnote ID="L41ecf77c-50b0-44b9-9918-cffb57a388ae">includes hot flush and flushing</footnote></td><td align="center"> 50</td><td align="center"> 0</td></tr><tr><td> Hypertension<footnote ID="L6fdafd2c-5439-4fb3-8c48-d4a1528eb44c">includes hypertension, essential hypertension, and blood pressure increased</footnote></td><td align="center"> 15</td><td align="center"> 0</td></tr><tr><td colspan="3"> General disorders and administration site conditions </td></tr><tr><td> Injection site reactions<footnote ID="L3a09fabe-cbd3-47d5-93ce-24bc32db7712">includes injection site pain, injection site erythema, injection site hemorrhage, injection site nodule, injection site paraesthesia, injection site pruritus, and injection site warmth</footnote></td><td align="center"> 11</td><td align="center"> 0</td></tr><tr><td> Fatigue<footnote ID="L2920987e-ee68-4277-9103-5b047c27f5ce">includes fatigue and asthenia</footnote></td><td align="center"> 10</td><td align="center"> 0</td></tr><tr><td colspan="3"> Infections and infestations </td></tr><tr><td> Upper respiratory tract infection<footnote ID="L047c54e6-3bc1-489e-b8c9-d5f591ca8f5d"> includes upper respiratory tract infection, sinusitis, and nasopharyngitis</footnote></td><td align="center"> 11</td><td align="center"> 0</td></tr><tr><td colspan="3"> Musculoskeletal and connective tissue disorders </td></tr><tr><td> Musculoskeletal pain<footnote ID="Ld88c5aae-b62d-4cb4-b9a4-0a8fc8030646">includes musculoskeletal pain, back pain, and bone pain</footnote></td><td align="center"> 11</td><td align="center"> 0</td></tr><tr><td> Pain in extremity</td><td align="center"> 10</td><td align="center"> 0</td></tr><tr><td> Arthralgia</td><td align="center"> 7</td><td align="center"> 0</td></tr><tr><td colspan="3"> Renal and urinary disorders </td></tr><tr><td> Micturition urgency<footnote ID="L8103d1b4-a143-4c30-84ae-0f4ae8d9c7de">includes micturition urgency and dysuria</footnote></td><td align="center"> 6</td><td align="center"> 0</td></tr><tr><td> Nocturia</td><td align="center"> 6</td><td align="center"> 0</td></tr><tr><td colspan="3"> Nervous system disorders </td></tr><tr><td> Dizziness<footnote ID="L4a73a862-0ec3-48ed-8d78-dcd4452d6427">includes dizziness, dizziness postural, vertigo, and vertigo positional.</footnote></td><td align="center"> 5</td><td align="center"> 0.7</td></tr></tbody></table>