CAMCEVI

CAMCEVI- leuprolide mesylate injection, emulsion
Foresee Pharmaceuticals Co., Ltd.

1 INDICATIONS AND USAGE

CAMCEVI is indicated for the treatment of adult patients with advanced prostate cancer.

2 DOSAGE AND ADMINISTRATION

2.1 Recommended Dosage

CAMCEVI must be administered by a healthcare provider.
The recommended dose of CAMCEVI is 42 mg administered subcutaneously once every 6 months.

2.2 Preparation and Administration

Syringe Assembly

1. Remove CAMCEVI kit from refrigerator. Open carton and remove blister.
2. Allow prefilled syringe to sit at room temperature for 30 minutes prior to subcutaneous injection.
3. Examine all contents of the package. Do not use if any component is damaged.
4. Check the expiration date on the syringe. Do not use if the expiration date has passed.
5. The use of gloves is recommended during syringe assembly and administration.
6. On a clean, dry surface, remove pre-filled syringe (A) and needle cartridge (B) from the blister carton. Visually inspect the contents prior to use.
7. Remove the gray cap from the syringe (A).
8. Twist the clear cap off the bottom of the needle cartridge (B).
9. Attach the needle (B) to the end of the syringe (A) by pushing and turning the needle until firmly connected to the syringe. Do not over twist the needle and strip the threading.

Remove contents	Syringe Assembly	Assembled Pre-Filled Syringe
		(click image for full-size original)

Administration Procedure

1. 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.
2. Pull the blue cover off the needle (B). Use standard sharps safety techniques to avoid needle sticks.
3. 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.
4. 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.

Prepare the Injection Site	Administer Treatment

Needle Protection

1. Do not remove the needle from the syringe. Use the enclosed Point-Lok^® device to prevent needle sticks.
2. Retrieve the Point-Lok® needle protection device from the Camcevi kit and place it on a secured, flat surface with its largest surface base touching the surface as shown in the diagram below.
3. Immediately after use of the needle, gently insert the exposed needle into the Point-Lok^® device opening at the top of the Point-Lok^® device. (see Figure 1 below)
4. Push the needle into the top opening until it is fully inserted into the Point-Lok® device. This action will seal the needle tip and lock the needle firmly into the Point-Lok^® device. (see Figure 2 below)

5. After use, place the used syringe with needle protected in a suitable sharps container. Dispose of contaminated product in a safe manner according to Centers for Disease Control and Prevention, USA and Federal/State/Local regulations (EPA,OSHA) and health care facility guidelines or local equivalent.

3 DOSAGE FORMS AND STRENGTHS

Injectable emulsion: 42 mg leuprolide (equivalent to approximately 48 mg leuprolide mesylate) as a sterile, off-white to pale yellow, viscous, and opalescent emulsion in a single-dose, pre-filled syringe for subcutaneous injection.

4 CONTRAINDICATIONS

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.

5 WARNINGS AND PRECAUTIONS

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)].