CAMCEVI

CAMCEVI is a sterile formulation of leuprolide mesylate for subcutaneous injection. CAMCEVI is designed to deliver approximately 42 mg of leuprolide over 6 months. Leuprolide mesylate is a synthetic nonapeptide analog of naturally occurring GnRH and is a GnRH agonist. The analog possesses greater potency than the natural hormone. The chemical name is 5-oxo-L-prolyl-L-histidyl-L-tryptophyl-L-seryl-L-tyrosyl-D-leucyl-L-leucyl-L-arginyl-N-ethyl-L-prolinamide mesylate (salt) with the following structural formula. The pH of 50 mg/mL solution of leuprolide mesylate in water is approximately 5.7. CAMCEVI is supplied as a kit with a pre-filled, single-dose, sterile syringe for subcutaneous injection. Each pre-filled syringe delivers 42 mg leuprolide (equivalent to approximately 48 mg leuprolide mesylate), poly(D, L-lactide) (184 mg) polymer and N -methyl-2-pyrrolidone (136 mg). camcevi-inj-structure-terumo-needle

CAMCEVI is indicated for the treatment of adult patients with advanced prostate cancer. CAMCEVI is a gonadotropin-releasing hormone (GnRH) agonist indicated for the treatment of adult patients with advanced prostate cancer.

See Full Prescribing Information for instructions on the preparation and administration of the injectable emulsion in a pre-filled syringe. ( 2 ) Recommended Dosage: 42 mg subcutaneously every 6 months. ( 2 ) 2.1 Recommended Dosage The recommended dose of CAMCEVI is 42 mg administered subcutaneously once every 6 months. 2.2 Preparation and Administration CAMCEVI must be administered by a healthcare provider. Important: Read the instructions completely before you administer Camcevi for the first time. Do NOT substitute any of the components from the kit for administration. CAMCEVI is packaged in a blister in the kit. Check to make sure the kit contains: One sterile, single-dose pre-filled syringe with plunger rod and backstop One sterile 18-gauge SurGuard®3 safety needle, 5/8-inch needle Prescribing Information Follow the detailed instructions to ensure correct preparation of CAMCEVI prior to administration: STEP 1 Remove CAMCEVI kit from refrigerator. Keep the contents in their original, sealed blister carton and allow to sit at room temperature for 30 minutes before use. Return to refrigerator after 30 minutes if not used. STEP 2 On a clean, dry surface, open carton and remove the contents. Examine all contents of the package. Do not use if any component is damaged. Check the expiration date on the syringe. Do not use if the expiration date has passed. The use of gloves is recommended during syringe assembly and administration. STEP 3 Remove pre-filled syringe (A) from the blister tray and open the safety needle (B) package by peeling back the paper tab. The safety needle (B) package is located beneath the blister tray. Visually inspect the syringe for particulate matter prior to administration. The emulsion should appear off-white to pale yellow, viscous, and opalescent. Do not use if particulate matter is observed prior to administration. STEP 4 Remove the gray cap from the syringe (A). Attach the needle (B) to the end of the syringe (A) by gently screwing clockwise with approximately a three-quarter turn until the needle is secure . Do not overtighten, as the needle hub may become damaged resulting in leakage of the product during injection. The safety sheath may also be damaged if the needle is overtightened onto the syringe. See figure of assembled pre-filled syringe below. STEP 5 Choose an injection site on the upper- or mid-abdominal area with sufficient soft or loose subcutaneous tissue that has not recently been used. Clean the injection site with an alcohol swab. Do NOT inject in areas with brawny or fibrous subcutaneous tissue or locations that can be rubbed or compressed (i.e., with a belt or clothing waistband). In addition, avoid applying heat directly to the site of Camcevi injection. STEP 6 (1) Move the safety sheath away from the needle and towards the syringe and (2) remove the clear needle cover immediately before injection. Note: Should the needle hub appear to be damaged, or leak, the product should NOT be used. The damaged needle should NOT be replaced and the product should NOT be injected. In the event of damage to the needle hub, use a new replacement CAMCEVI kit. STEP 7 Use standard aseptic technique when performing the injection. Grab and bunch the skin around the injection site with one hand. Insert the needle at a 90° angle to the skin surface, and then release the bunched skin. STEP 8 Inject the full contents of the syringe with a slow and steady push on the plunger, and then withdraw the needle at the same 90° angle used for insertion. STEP 9 Immediately following the withdrawal of the needle, activate the safety sheath using a finger/thumb or flat surface and push until it completely covers the needle tip and locks into place. An audible and tactile “click” verifies a locked position. Check to confirm the safety sheath is fully engaged. STEP 10 After use, discard all components safely in a suitable sharps container. Dispose of the syringe and contaminated products according to local regulations/procedures. camcevi-inj-image-2-terumo-needle camcevi-inj-image-3-terumo-needle camcevi-inj-image-4-terumo-needle camcevi-inj-image-9-terumo-needle camcevi-inj-image-5-terumo-needle.jpg camcevi-inj-image-6-terumo-needle camcevi-inj-image-7-terumo-needle camcevi-inj-image-8-terumo-needle

CAMCEVI is contraindicated in patients known to be hypersensitive to GnRH, GnRH agonist analogs, or any of the excipients in CAMCEVI. Anaphylactic reactions to GnRH agonist analogs have been reported in the medical literature. Hypersensitivity to GnRH, GnRH agonist analogs, or any of the components of CAMCEVI. ( 4 )

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 (≥5%) adverse reactions were hot flushes, hypertension, injection site reactions, fatigue, upper respiratory tract infections, musculoskeletal pain, pain in extremity, arthralgia, micturition urgency, nocturia, and dizziness. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Accord BioPharma Inc. 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. FP01C-13-001 The safety of CAMCEVI was evaluated in an open-label, single-arm, international clinical trial (FP01C-13-001) in patients with advanced prostate cancer. Patients 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 CAMCEVI in Advanced Prostate Cancer Patients - FP01C-13-001 Adverse Reaction CAMCEVI N=137 All Grades (%) Grade 3-4 (%) Vascular disorders Hot flushes a 50 0 Hypertension b 15 0 General disorders and administration site conditions Injection site reactions c 11 0 Fatigue d 10 0 Infections and infestations Upper respiratory tract infection e 11 0 Musculoskeletal and connective tissue disorders Musculoskeletal pain f 11 0 Pain in extremity 10 0 Arthralgia 7 0 Renal and urinary disorders Micturition urgency g 6 0 Nocturia 6 0 Nervous system disorders Dizziness h 5 0.7 a includes hot flush and flushing b includes hypertension, essential hypertension, and blood pressure increased c includes injection site pain, injection site erythema, injection site hemorrhage, injection site nodule, injection site paraesthesia, injection site pruritus, and injection site warmth d includes fatigue and asthenia e includes upper respiratory tract infection, sinusitis, and nasopharyngitis f includes musculoskeletal pain, back pain, and bone pain g includes micturition urgency and dysuria h includes dizziness, dizziness postural, vertigo, and vertigo positional. 6.2 Postmarketing Experience The following adverse reactions have been identified during post approval use of CAMCEVI or 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: hypersensitivity reactions including anaphylaxis, 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: leukopenia 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 induration or swelling, SJS/TEN, DRESS, AGEP, dermatitis exfoliative, bullous dermatitis, and erythema multiforme Urogenital System: prostate pain