Gemzar 200mg. 1000mg Injection

GEMZAR is indicated for the treatment of patients with locally advanced or metastatic non-small cell lung cancer.

GEMZAR is indicated as first-line treatment for patients with locally advanced (non-resectable Stage II or Stage III) or metastatic (Stage IV) adenocarcinoma of the pancreas. GEMZAR is indicated for patients previously treated with 5-FU.

GEMZAR is indicated for treatment of patients with transitional cell bladder cancer.

GEMZAR, in combination with paclitaxel, is indicated for the treatment of patients with unresectable, locally recurrent or metastatic breast cancer who have relapsed following adjuvant/neoadjuvant chemotherapy. Prior chemotherapy should have included an anthracycline unless clinically contra-indicated.

GEMZAR, alone or in combination, is indicated for the treatment of patients with recurrent epithelial ovarian carcinoma who have relapsed following platinum-based chemotherapy.

GEMZAR is for intravenous use only.

Patients with hepatic or renal impairment: GEMZAR should be used with caution in patients with hepatic insufficiency or with impaired renal function as no studies have been done in patients with significant renal or hepatic impairment. There is insufficient information from clinical studies to allow clear dose recommendation for this patient population.

Non-small cell lung cancer: Adults: The recommended monochemotherapy dosage is 1 000 mg/mu00b2, given by 30 minute intravenous infusion. This should be repeated once weekly for three weeks, followed by a one week rest period. This four week cycle is then repeated. Dosage reduction with each cycle or within a cycle may be applied based upon the amount of toxicity experienced by the patient.

GEMZAR may be used in combination with cisplatin using either a three week or a four week schedule. One of the following regimens is suggested:

• 3 week schedule: GEMZAR 1 250 mg/mu00b2, given by 30 minute intravenous infusion on days 1 and 8 of every 21 day cycle and cisplatin 100 mg/mu00b2 on day 1. Dosage reduction with each cycle or within a cycle may be applied based upon the amount of toxicity experienced by the patient.
• 4 week schedule: GEMZAR 1 000 mg/mu00b2 on days 1, 8 and 15 of every 28 day cycle and cisplatin 100 mg/mu00b2 on either day 1, 2 or 15 of therapy. Dose reduction with each cycle or within a cycle may be applied based upon the amount of toxicity experienced by the patient.

Pancreatic cancer: Adults: The recommended dose of GEMZAR is 1 000 mg/mu00b2, given by 30 minute intravenous infusion. This should be repeated once weekly for up to 7 weeks followed by a week of rest. Subsequent cycles should consist of injections once weekly for 3 consecutive weeks out of every 4 weeks. Dosage reduction with each cycle or within a cycle may be applied based upon the amount of toxicity experienced by the patient.

Bladder cancer: Adults: The recommended monochemotherapy dosage of GEMZAR is 1 250 mg/mu00b2, given by 30 minute intravenous infusion. The dose should be given on days 1, 8 and 15 of each 28 day cycle. This four week cycle is then repeated. Dosage reduction with each cycle or within a cycle may be applied based upon the amount of toxicity experienced by the patient.

GEMZAR may be used in combination with cisplatin. The recommended dose of GEMZAR is 1 000 mg/mu00b2, given by 30 minute infusion. The dose should be given on days 1, 8 and 15 of each 28 day cycle in combination with cisplatin. Cisplatin is given at a recommended dose of 70 mg/mu00b2 on day 1 following GEMZAR or day 2 of each 28 day cycle. This four week cycle is then repeated. Dosage reduction with each cycle or within a cycle may be applied based upon the amount of toxicity experienced by the patient. A clinical trial showed more myelosuppression when cisplatin was used in doses of 100 mg/mu00b2.

Breast cancer: Adults: GEMZAR in combination with paclitaxel is recommended using paclitaxel (175 mg/mu00b2) administered on day 1 over approximately 3 hours as an intravenous infusion, followed by GEMZAR (1 250 mg/mu00b2) as a 30 minute intravenous infusion on days 1 and 8 of each 21 day cycle. Dose reduction with each cycle or within a cycle may be applied based upon the amount of toxicity experienced by the patient. Patients should have an absolute granulocyte count of at least 1 500 (x 10 6 /L) prior to initiation of GEMZAR + paclitaxel combination.

Ovarian Cancer: Single agent use: Adults: The recommended dose of GEMZAR is 800 to 1 250 mg/mu00b2, given by a 30 minute intravenous infusion. The dose should be given on days 1, 8 and 15 of each 28 day cycle. This four week cycle is then repeated. Dosage reduction with each cycle or within a cycle may be applied based upon the amount of toxicity experienced by the patient.

Combination use: Adults: GEMZAR in combination with carboplatin is recommended using GEMZAR 1 000 mg/mu00b2 administered on days 1 and 8 of each 21 day cycle as a 30 minute intravenous infusion. After GEMZAR, carboplatin will be given on day 1 consistent with a target AUC of 4,0 g/ml/min. Dosage reduction with each cycle or within a cycle may be applied based upon the amount of toxicity experienced by the patient.

Patients receiving GEMZAR should be monitored prior to each dose for platelet, leucocyte and granulocyte counts and, if necessary, the dose of GEMZAR may be either reduced or withheld in the presence of haematological toxicity, according to the following scale:

Absolute granulocyte count (x 10 6 /L) Platelet count (x 10 6 /L) % of full dose

• >1 000 >100 000 100
• 500 - 1 000 50 000 - 100 000 75
• <500 <50 000 hold

Periodic physical examination and checks of renal and hepatic function should be made to detect non-haematologic toxicity. Dosage reduction with each cycle or within a cycle may be applied based upon the amount of toxicity experienced by the patient. Doses should be withheld until toxicity has resolved in the opinion of the physician.

GEMZAR is well tolerated during the infusion, with only a few cases of injection site reaction reported. GEMZAR can be easily administered on an outpatient basis.

Elderly patients: GEMZAR has been well tolerated in patients over the age of 65. There is no evidence to suggest that dose adjustments are necessary in the elderly, although GEMZAR clearance and half-life are affected by age.

Instructions for reconstitution: The only approved diluent for reconstitution of GEMZAR is 0,9% sodium chloride injection without preservatives. It is not recommended that GEMZAR be mixed with other medicines when reconstituted. Due to solubility considerations, the maximum concentration for GEMZAR upon reconstitution is 40 mg/ml. Reconstitution at concentrations greater than 40 mg/ml may result in incomplete dissolution and should be avoided. To reconstitute, add at least 5 ml of 0,9 % sodium chloride injection without preservatives to the 200 mg vial or at least 25 ml of 0,9 % sodium chloride injection without preservatives to the 1 g vial. Shake to dissolve. The appropriate amount of medicine may be administered as prepared or further diluted with 0,9 % sodium chloride injection without preservatives.

GEMZAR is contra-indicated in those patients with a known hypersensitivity to the medicine.

Pregnancy and lactation: The safety of GEMZAR in human pregnancy and lactation has not been established.

Usage in children: Safety and effectiveness in children have not been established.

Prolongation of the infusion time and increased dosing frequency have been shown to increase toxicity. GEMZAR can suppress bone marrow function as manifested by leucopoenia, thrombocytopenia and anaemia. Myelosuppression is usually mild to moderate and is more pronounced for the granulocyte count (see u2018DOSAGE AND DIRECTIONS FOR USEu2019 and u2018Side effects - Haematological Toxicityu2019).

RADIOTHERAPY: CONCURRENT (GIVEN TOGETHER OR u2264 7 DAYS APART) - TOXICITY ASSOCIATED WITH THIS MULTIMODALITY THERAPY IS DEPENDENT ON MANY DIFFERENT FACTORS, INCLUDING DOSE OF GEMZAR, FREQUENCY OF GEMZAR ADMINISTRATION, DOSE OF RADIATION, RADIOTHERAPY PLANNING TECHNIQUE, THE TARGET TISSUE, AND TARGET VOLUME. PRE-CLINICAL AND CLINICAL STUDIES HAVE SHOWN THAT GEMZAR HAS RADIOSENSITIZING ACTIVITY. IN A SINGLE TRIAL, WHEN GEMZAR AT A DOSE OF 1 000 mg/mu00b2 WAS ADMINISTERED CONCURRENTLY FOR UP TO 6 CONSECUTIVE WEEKS WITH THERAPEUTIC THORACIC RADIATION TO PATIENTS WITH NON-SMALL CELL LUNG CANCER, SIGNIFICANT TOXICITY IN THE FORM OF SEVERE AND POTENTIALLY LIFE THREATENING MUCOSITIS, ESPECIALLY ESOPHAGITIS, AND PNEUMONITIS WAS OBSERVED, PARTICULARLY IN PATIENTS RECEIVING LARGE VOLUMES OF RADIOTHERAPY (MEDIAN TREATMENT VOLUMES 4 795 cmu00b3). THE OPTIMUM REGIMEN FOR SAFE ADMINISTRATION OF GEMZAR WITH THERAPEUTIC DOSES OF RADIATION HAS NOT YET BEEN DETERMINED IN ALL TUMOUR TYPES. RADIATION INJURY HAS BEEN REPORTED ON TARGETED TISSUES (e.g. ESOPHAGITIS, COLITIS, AND PNEUMONITIS) IN ASSOCIATION WITH BOTH CONCURRENT AND NON-CONCURRENT USE OF GEMZAR.

The safety of GEMZAR in human pregnancy and lactation has not been established. See u2018CONTRA - INDICATIONSu2019.

GEMZAR has been reported to cause mild to moderate somnolence. Patients should be cautioned against driving or operating machinery until it is established that they do not become somnolent.

The most commonly reported adverse drug reactions associated with GEMZAR treatment include nausea with or without vomiting, raised liver transaminases (AST/ALT) and alkaline phosphatase, reported in approximately 60 % of patients, proteinuria and haematuria reported in approximately 50% of patients, dyspnoea reported in 10 to 40 % of patients (highest incidence in lung cancer patients) and allergic skin rashes occurring in approximately 25 % of patients and associated with itching in 10% of patients. The frequency and severity of adverse reactions are affected by the dose, infusion rate and intervals between doses (see u2018WARNINGSu2019). Dose-limiting adverse reactions are reductions in platelet, leucocyte and granulocyte counts (see u2018DOSAGE AND DIRECTIONS FOR USEu2019).

The following listing of undesirable effects and frequencies is based on clinical trial and post-marketing spontaneous reports.

Blood and Lymphatic System Disorders

• Very Common (>1:10): Leucopenia, thrombocytopenia, anaemia. (Neutropenia Grade 3 = 19,3 %; Grade 4 = 6 %). Myelosuppression is usually transient, usually does not result in dose reductions and rarely results in discontinuation. Dosage reduction or omission may be necessary for severe bone marrow depression (see u2018DOSAGE AND DIRECTIONS FOR USEu2019.)
• Common (>1:100, <1:10): Febrile neutropenia.

Immune System Disorders

• Very Rare (<1:10 000): Anaphylactoid reaction (see u2018CONTRA - INDICATIONSu2019).

Nervous System Disorders

• Common (>1:100, <1:10): Somnolence.

Cardiac Disorders

• Rare (>1:10 000, <1:1 000): Myocardial infarct, heart failure, arrhythmia (predominantly supraventricular in nature).

Vascular Disorders

• Rare (>1:10 000, <1:1 000): Hypotension.
• Very Rare (<1:10 000): Clinical signs of peripheral vasculitis and gangrene.

Respiratory, Thoracic and Mediastinal Disorders

• Very Common (>1:10): Dyspnoea. Usually mild and short-lived, rarely dose-limiting, and usually abates without any specific therapy.
• Uncommon (>1:1 000, <1:100): Bronchospasm. Usually mild and transient, but parenteral therapy may be required.
• Rare (>1:10 000, <1:1 000): Pulmonary oedema, interstitial pneumonitis (with associated pulmonary infiltrates), adult respiratory distress syndrome (ARDS). (See u2018PRECAUTIONSu2019.)

Gastrointestinal Disorders

• Very Common (>1:10): Nausea, vomiting. These adverse events require therapy in about 20% of patients, are rarely dose-limiting and are easily manageable with standard antiemetics. Stomatitis.
• Common (>1:100, <1:10): Diarrhoea, constipation.

Hepatobiliary Disorders

• Very Common (>1:10): Elevation of liver transaminases (AST and ALT) and alkaline phosphatase.
• Rare (>1:10 000, <1:1 000): Increased gamma-glutamyl transferase (GGT) and bilirubin.

Skin and Subcutaneous Tissue Disorders

• Very Common (>1:10): Allergic skin rash, frequently associated with pruritus. The rash is usually mild, not dose-limiting and responsive to local therapy. Alopecia.
• Rare (>1:10 000, <1:1 000): Scaling, vesicle and sore formation, ulceration.
• Very Rare (<1:10 000): Severe skin reactions, including desquamation and bullous skin eruptions.

Renal and Urinary Disorders

• Very Common (>1:10): Mild proteinuria and haematuria. Rarely clinically significant and not usually associated with any change in serum creatinine or blood urea nitrogen.
• Rare (>1:10 000, <1:1 000): Renal failure (aetiology unknown). Haemolytic uraemic syndrome (HUS) (see u2018PRECAUTIONSu2019 - u2018Renal toxicityu2019). GEMZAR should be used with caution in patients with impaired renal function (see u2018PRECAUTIONSu2019 u2013 u2018Patients with renal or hepatic impairmentu2019).

General Disorders and Administration Site Conditions

• Very Common (>1:10): Oedema/peripheral oedema. Usually mild to moderate, rarely dose-limiting, and usually reversible after stopping GEMZAR treatment. The mechanism of the toxicity is unknown. It is not associated with any evidence of cardiac, hepatic or renal failure.
• Influenza-like symptoms. The most common symptoms are fever, headache, back pain, shivering, muscle pain, asthenia and anorexia. Cough, rhinitis, malaise, perspiration and sleeping difficulties have also been reported. Fever and asthenia also occur as isolated symptoms. The mechanism of this toxicity is unknown.
• Common (>1:100, <1:10): Fever, asthenia.
• Very Rare (<1:10 000): Facial oedema.

Injury, Poisoning and Procedural Complications

• Radiosensitisation and radiation recall reactions have been reported (also see u2018INTERACTIONSu2019).

There is no antidote for overdosage of GEMZAR. In the event of suspected overdose, the patient should be monitored with appropriate blood counts and should receive supportive therapy, as necessary.