1 NEW ZEALAND DATA SHEET 1. PRODUCT NAME ZOLACOS CP 3.6 mg + 50 mg Combination pack ZOLACOS CP 10.8 mg + 50 mg Combination pack 2. QUALITATIVE AND QUANTITATIVE COMPOSITION ZOLACOS CP is a combination therapy containing Zoladex (goserelin) 3.6 mg or 10.8 mg subcutaneous implant plus Cosudex (bicalutamide) 50 mg tablets. BICALUTAMIDE COSUDEX 50 mg is a white film-coated tablet containing 50 mg bicalutamide and is impressed with CDX50 on one side and a logo on the other. GOSERELIN A sterile, white to cream coloured cylindrical implant in which goserelin acetate (equivalent to 3.6 mg or 10.8 mg of peptide base) is dispersed in a biodegradable matrix. It is supplied in a single dose syringe applicator. The SafeSystemTM incorporates a protective needle sleeve that automatically locks in place following administration of the implant to aid in the prevention of needle stick injury. 3. PHARMACEUTICAL FORM Combination pack. 4. CLINICAL PARTICULARS 4.1 THERAPEUTIC INDICATIONS ZOLACOS CP is indicated for the treatment of advanced prostate cancer and prevention of disease flare associated with the use of luteinizing-hormone releasing hormone (LHRH) agonists. 4.2 DOSE AND METHOD OF ADMINISTRATION Adult males including the elderly Bicalutamide (Cosudex): One tablet (50 mg) once a day. Treatment with Cosudex should be started at the same time as treatment with Zoladex. Goserelin (Zoladex): One 3.6 mg implant of goserelin every 28 days or one 10.8 mg implant of goserelin every 3 months, injected subcutaneously into the anterior abdominal wall. ZOLACOS CP Data Sheet 010817 Copyright 2 Children ZOLACOS CP is contraindicated in children. Renal and hepatic Impairment No dosage adjustment is necessary for patients with renal or hepatic impairment. Increased accumulation of bicalutamide may occur in patients with moderate to severe hepatic impairment (see WARNINGS AND PRECAUTIONS). Method of administration Goserelin (Zoladex) For correct administration of ZOLADEX, see instructions on the pouch/carton. Use as directed by the prescriber. Use extra care when administering ZOLADEX to patients with a low BMI and/or who are receiving full anticoagulation medication (see WARNINGS AND PRECAUTIONS). Use only if pouch is undamaged. Use immediately after opening pouch. The following information is intended for medical or healthcare professionals only: ZOLADEX is administered by subcutaneous injection - read and understand all the instructions fully prior to administration 1. Put the patient in a comfortable position with the upper part of the body slightly raised. Prepare the injection site according to the local policy and procedure. NOTE: Caution should be taken while injecting ZOLADEX into the anterior abdominal wall due to the proximity of underlying inferior epigastric artery and its branches; very thin patients may be at higher risk of vascular injury. 2. Examine the foil pouch and syringe for damage. Remove the syringe from the opened foil pouch and hold the syringe at a slight angle to the light. Check that at least part of the ZOLADEX implant is visible. (Figure 1). Figure 1. 3. Grasp the plastic safety tab and pull away from the syringe, and discard. (Figure 2). Remove needle cover. Unlike liquid injections, there is no need to remove air bubbles as attempts to do so may displace the ZOLADEX implant. ZOLACOS CP Data Sheet 010817 Copyright 3 Figure 2. 4. Holding the syringe around the protective sleeve, using an aseptic technique, pinch the patient’s skin and insert the needle at a slight angle (30 to 45 degrees) to the skin. With the opening of the needle facing up, insert needle into the subcutaneous tissue of the anterior abdominal wall below the navel line, until the protective sleeve touches the patient’s skin. (Figure 3). Figure 3. NOTE: The ZOLADEX syringe cannot be used for aspiration. If the hypodermic needle penetrates a large vessel, blood will be seen instantly in the syringe chamber. If a vessel is penetrated, withdraw the needle and immediately control any resultant bleeding, monitoring the patient for signs or symptoms of abdominal haemorrhage. After ensuring the patient is haemodynamically stable another ZOLADEX implant may be injected with a new syringe elsewhere. Use extra care when administering ZOLADEX to patients with a low BMI and/or to patients receiving full dose anticoagulation. 5. Do not penetrate into muscle or peritoneum. Incorrect grip and angle of presentation is shown (Figure 4.) Figure 4. 6. Depress the plunger fully, until you can depress no more, to discharge the ZOLADEX implant and to activate the protective sleeve. You may hear a ‘click’ and will feel the protective sleeve automatically begin to slide to cover the needle. If the plunger is not depressed fully, the protective sleeve will NOT activate. NOTE: The needle does not retract. ZOLACOS CP Data Sheet 010817 Copyright 4 7. Holding the syringe as shown in Figure 5, withdraw the needle and allow protective sleeve to continue to slide and cover needle. 1. Dispose of the syringe in an approved sharps collector. Figure 5. NOTE: In the unlikely event of the need to surgically remove a ZOLADEX implant, it may be localized by ultrasound. Before injection, it should be ensured that the implant is visible in the window of the applicator. The plunger should not be withdrawn once the needle is in position. The plunger should be fully depressed to expel the implant into the subcutaneous tissue well away from point of entry and to activate the protective needle sleeve. For correct administration of ZOLADEX, see instructions on the administration card. 4.3 CONTRAINDICATIONS Bicalutamide Bicalutamide is contraindicated in females and children. Bicalutamide must not be given to any patient who has shown a hypersensitivity reaction to the active substance or to any of the excipients. Goserelin Known severe hypersensitivity to the active substance or to any of the excipients of this product. 4.4 SPECIAL WARNINGS AND PRECAUTIONS FOR USE Androgen deprivation therapy may prolong the QT interval, although a causal association has not been established with ZOLACOS CP. In patients with a history of or who have risk factors for QT prolongation and in patients receiving concomitant medicinal products that may prolong the QT interval (see section 4.5) physicians should assess the benefit risk ratio including the potential for Torsade de Pointes prior to initiating ZOLACOS CP. Bicalutamide Bicalutamide is extensively metabolised in the liver. Data suggest that its elimination may be slower in subjects with severe hepatic impairment and this could lead to increased accumulation of bicalutamide. Therefore, COSUDEX should be used with caution in patients with moderate to severe hepatic impairment. ZOLACOS CP Data Sheet 010817 Copyright 5 Periodic liver function testing should be considered due to the possibility of hepatic changes. Severe hepatic changes and hepatic failure have been observed rarely with bicalutamide and fatal outcomes have been reported (see section 4.8). COSUDEX therapy should be discontinued if changes are severe. Antiandrogen therapy may cause morphological changes in spermatozoa. Although the effect of bicalutamide on sperm morphology has not been evaluated and no such changes have been reported for patients who received COSUDEX, patients and/or their partners should use adequate contraception methods during and for 130 days after COSUDEX therapy. Potentiation of coumarin anticoagulant effects have been reported in patients receiving concomitant COSUDEX therapy, which may result in increased Prothrombin Time (PT) and International Normalised Ratio (INR). Some cases have been associated with risk of bleeding. Close monitoring of PT/INR is advised and anticoagulant dose adjustment should be considered (see sections 4.5 and 4.8). Goserelin The use of ZOLADEX in men at particular risk of developing ureteric obstruction or spinal cord compression should be considered carefully and the patients monitored closely during the first month of therapy. If spinal cord compression or renal impairment due to ureteric obstruction are present or develop, specific standard treatment of these complications should be instituted. Isolated cases have been reported. Initially ZOLADEX, like other LHRH agonists, transiently increases serum testosterone. Some patients may experience a temporary increase in bone pain, which can be managed symptomatically. A reduction in glucose tolerance has been observed in males receiving LHRH agonists. This may manifest as diabetes or loss of glycaemic control in those with pre-existing diabetes mellitus. Consideration should therefore be given to monitoring blood glucose. An increased risk of developing myocardial infarction and sudden cardiac death 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. The use of LHRH agonists may cause a reduction in bone mineral density. In men, preliminary data suggest the use of a bisphosphonate in combination with a LHRH agonist may reduce bone mineral loss. ZOLADEX is not indicated for use in children as safety and efficacy has not been established in this group of patients. 4.5 INTERACTION WITH OTHER MEDICINES AND OTHER FORMS OF INTERACTION Since androgen deprivation treatment may prolong the QT interval, the concomitant use of ZOLACOS CP with medicinal products known to prolong the QT interval or medicinal products able to induce Torsade de Pointes should be carefully evaluated (see WARNINGS AND PRECAUTIONS). ZOLACOS CP Data Sheet 010817 Copyright 6 Bicalutamide In vitro studies have shown that R-bicalutamide is an inhibitor of CYP3A4, with lesser inhibitory effects on CYP 2C9, 2C19 and 2D6 activity. Although in vitro studies have suggested the potential for bicalutamide to inhibit cytochrome 3A4, a number of clinical studies show the magnitude of any inhibition is unlikely to be of clinical significance.