COMPOSITION
Each vial contains :
Gemcitabine hydrochloride equivalent to 1000 mg Gemcitabine.
INDICATIONS
Therapeutic indications
Non-Small Cell Type Lung Cancer :
Gemcitabine is indicated for palliative therapy in adult patients with locally advanced or metastatic non-small cell lung cancer.
Pancreatic Cancer :
Gemcitabine is indicated as first-line therapy for patients with locally advanced (stage II or stage III non-resectable) or metastatic (stage IV) pancreatic adenocarcinoma. Gemcitabine is indicated for patients previously treated with 5-FU.
Bladder Cancer :
Gemcitabine is indicated for the treatment of advanced bladder cancer (stage IV muscle – invasive tumor with or without metastasis) in combination with cisplatin therapy.
CONTRAINDICATION
Gemcitabine is contraindicated in patients with known hypersensitivity to this drug.
POSOLOGY/METHOD OF ADMINISTRATION
Non-Small Cell Type Lung Cancer :
Usage as a sole agent : Adults : The recommended dose of Gemcitabine is 1000 mg/m2, given by intravenous infusion over 30 minutes. This administration should be repeated once a week for three weeks, followed by a one week rest period. This four-week cycle is then repeated. The dose reduction can be made based on the amount of toxicity experienced by the patient.
Pancreatic Cancer : Adults : The recommended dose of Gemcitabine is 1000 mg/m2, given by intravenous infusion over 30 minutes. This administration should be repeated once a week for 7 weeks, followed by a one week rest period. The next cycle should include the injection once a week for 3 consecutive weeks every 4 weeks. The dose reduction can be made based on the level of toxicity experienced by the patient.
Bladder Cancer : Combination use : Adults : The recommended dose of Gemcitabine is 1000 mg/m2, given intravenously for 30 minutes. This dose should be administered on days 1, 8, and 15 of each 28 day cycle in combination with Cisplatin given in the recommended dose of 70 mg/m2 on day 1 after Gemcitabine administration or day 2 of each 28 day cycle. Myelosuppression is more common when Cisplatin is used in doses of 100 mg/m2.
Patients receiving Gemcitabine should have their platelet, leucocyte and granulocyte count monitored before each dose and if necessary, the Gemcitabine dose can be reduced or delayed in the presence of haematological toxicity, according to the following scale :
| Absolute number of granulocytes (x 106/l) | Platelet count (x 106/l) | % of the full dose |
| > 1,000 | > 100,000 | 100 |
| 500 – 1,000 | 50,000 – 100,000 | 75 |
| < 500 | < 50,0000 | delayed |
For adjustment of the dose of Cisplatin in combination therapy, see the information available from the manufacturer. Periodic liver and kidney function tests, including transaminases and serum creatinine, should also be performed in patients receiving Gemcitabine.
Gemcitabine was well tolerated during infusion with only a few cases of injection site reactions reported. No reports of necrosis at the injection site. Gemcitabine can be given on an outpatient basis.
Elderly patients : Gemcitabine is well tolerated in patients over 65 years of age. There is no evidence that dose adjustment is necessary in elderly patients, although the clearance and half-life of Gemcitabine are affected by age.
Children : Gemcitabine has not been studied in children.
Liver and kidney disorders: Gemcitabine should be used with caution in patients with liver disorders or with impaired kidney function.
Radical radiotherapy: Gemcitabine should not be used in conjunction with radical radiotherapy.
INSTRUCTIONS FOR USE/HANDLING
Handling
Normal safety precautions for cytostatic agents must be observed when preparing and disposing of intravenous solutions. Handling of solutions for infusion should be carried out in a safety box and protective coats and gloves should be used. If there is no safety box, the equipment must be equipped with a mask and goggles.
If the preparation comes into contact with the eyes, it may cause serious irritation. Immediately flush eyes with water. If there is irritation that lasts for a long time, consult a doctor. If the liquid is spilled on the skin, rinse with water.
Instructions for reconstitution (and further dilution, if applicable)
The only diluent approved for Gemcitabine reconstitution is 9 mg/ml (0.9%) sodium chloride solution for injection (without preservative). Based on solubility, the maximum concentration for Gemcitabine after reconstitution is 40 mg/ml. Reconstitution at a concentration greater than 40 mg/ml can cause imperfect solutions and should be avoided.
- Use aseptic techniques during reconstitution and dilution of Gemcitabine for intravenous infusion.
- For reconstitution, add 5 ml of 9 mg/ml (0.9%) sterile sodium chloride solution for injection, without preservative, to a 200 mg bottle or 25 ml of 9 mg/ml (0.9%) sterile sodium chloride solution solution for injection, without preservatives, into a 1,000 mg vial. The total volume after reconstitution was 5.26 ml (200 mg vial) or 26.3 ml (1,000 mg vial), respectively. This yields a Gemcitabine concentration of 38 mg/ml, which includes the calculation of the volume displacement of the lyophilis powder. Shake until dissolved. Further dilution with sterile 9 mg/ml (0.9%) sodium chloride solution for injection, without preservative, is possible. The reconstituted solution is a clear colored solution that is colorless to yellowish.
- Parenteral medicinal products should be checked visually for particulate problems and discoloration prior to administration. If there are particles in the solution, do not apply. Any unused products or waste materials must be disposed of in accordance with local requirements.
INCOMPATIBILITIES
Compatibility with other drugs has not been studied.
WARNING AND PRECAUTIONS
Prolonged infusion time and increased dose frequency are known to cause increased toxicity. Gemcitabine can suppress bone marrow function resulting in leukopenia, thrombocytopenia and anemia. However, myelosuppression is short-lived and usually does not require dose reduction and therapy is rarely discontinued.
Gemcitabine should be discontinued if early signs of microangiopathic hemolytic anemia, such as rapid hemoglobin with thrombocytopenia, elevated serum bilirubin, serum creatinine, blood urea nitrogen, or LDH, are observed, which may indicate a decrease in the occurrence of hemolytic uremic syndrome. Renal failure that occurs is not reversible even with discontinuation of therapy, and dialysis may be required. Gemcitabine should not be given concurrently with radicals, as opposed to palliative, radiotherapy.
Precaution
General : Patients receiving therapy with Gemcitabine should be monitored closely. Laboratory facilities should be available to monitor patient status. Therapy for patients experiencing drug toxicity may be necessary.
Laboratory studies : Therapy should be initiated cautiously in patients with impaired bone marrow function. As with other oncolytics, the possibility of cumulative bone marrow suppression when using combination chemotherapy or sequential chemotherapy should be considered.
Patients receiving Gemcitabine should have their platelet, leucocyte and granulocyte count checked before each dose. Delay or modification of therapy should be considered if drug-induced bone marrow compression is found. Guidelines on dosage modification are provided in the dosage/mode of administration section. Peripheral blood counts may continue to decline after the drug is stopped.
PREGNANCY AND LACTATION
The use of Gemcitabine should be avoided in pregnant or nursing women because of the potential hazard to the fetus or infant.
EFFECTS ON ABILITY TO DRIVE AND USE MACHINES
Patients should be cautioned against driving or operating machinery until it is established that they do not become somnolent.
ADVERSE EFFECTS
Hematology :
Because Gemcitabine is a bone marrow suppressant, anemia, leukopenia and thrombocytopenia can occur as a result of Gemcitabine administration. Myelosuppression is generally mild to moderate in nature and is more pronounced for the number of granulocytes. Thrombocythemia is also frequently reported. Febrile neutropenia.
Gastrointestinal :
Liver transaminase enzyme abnormalities are generally mild, non-progressive and rarely require discontinuation of therapy. However, Gemcitabine should be used with caution in patients with impaired liver function.
Nausea and nausea accompanied by vomiting. These side effects require therapy in the patient, are rarely dose-limiting and are easily managed with standard anti-emetics.
Kidney :
Proteinuria and mild hematuria are rarely clinically significant and are generally not associated with changes in serum creatinine or blood urea nitrogen. However, some cases of kidney failure have no definite cause, including in very rare cases uremic hemolytic syndrome (signs of hemolytic microangiopathy) such as a rapid decrease in hemoglobin along with thrombocytopenia, an increase in serum bilirubin, serum creatinine, blood urea nitrogen or LDH . Therefore, Gemcitabine should be used with caution in patients with impaired renal function.
Allergic :
Rash was seen in some patients and associated with pruritus in some patients. The rash is generally mild, is not dose limited, and responds to local therapy. Desquamation, vesiculation and ulceration were rarely reported. Anaphylaxis was rarely reported.
Respiratory :
Bronchospasm after Gemcitabine infusion is generally mild and transient, but parenteral therapy may be required. Gemcitabine should not be given to patients who are known to be hypersensitive to this drug.
Shortness of breath that occurs within a few hours after injection of Gemcitabine is generally mild, of short duration, is rarely dose-limited and generally improves without specific therapy. The mechanism of this event is unknown and its association with Gemcitabine is unclear. Pulmonary effects that are sometimes severe (such as pulmonary edema, interstitial pneumonitis, or adult respiratory distress syndrome (ARDS), have been reported although they are rarely associated with Gemcitabine therapy. The cause of these effects is not known. If these effects occur, consideration should be given to discontinuing Gemcitabine administration. Early supportive care measures can help improve the condition.
Other effects :
Influenza-like symptoms are generally mild, short-lived and rarely dose-limited. Fever, headache, back pain, chills, myalgia, asthenia and anorexia are the symptoms most commonly reported. Cough, rhinitis, malaise, sweating and insomnia are also frequently reported.
Fever and asthenia are also frequently reported as isolated symptoms. The mechanism of this toxicity is unknown. Paracetamol can help relieve symptoms. Edema/peripheral edema and facial edema have also been reported. Pulmonary edema is reported rarely. Pulmonary edema/edema is reported rarely. Edema/peripheral edema is generally mild to moderate, rarely limited in dose, is sometimes reported as pain relief and is generally reversible after discontinuation of Gemcitabine therapy.
The mechanism of this toxicity is unknown. It is not associated with heart, liver or kidney failure.
The following side effects are also frequently reported : alopecia (usually minimal hair loss), somnolence, diarrhea, oral toxicity (especially pain and erythema) and constipation, radiation toxicity.
Several cases of hypotension have been reported. Myocardial infarction, congestive heart failure and arrhythmias have been reported but there is no clear evidence that Gemcitabine causes cardiac toxicity.
DRUG INTERACTION
No drug interactions were reported.
OVERDOSE
There is no known antidote for Gemcitabine overdose. A single dose of 5.7 g/m2 is given by IV infusion over 30 minutes every two weeks with clinically acceptable toxicity. If an overdose is suspected, the patient should be monitored for an appropriate blood count and given adjuvant therapy if necessary.
STORAGE
Store below 30°C.
Gemcitabine for injection is stable after reconstitution and dilution with 0.9 % Sodium Chloride solution for 24 hours stored below 30°C.
PRESENTATION AND REGISTRATION NUMBER
Gemcitabine for Injection 1000 mg
Each vial contains :
Gemcitabine hydrochloride USP equivalent to
Gemcitabine ……….. 1.00 g
Mannitol USP …….. 1.00 g
Sodium Acetate Anhydrous USP ……. 62.5 mg
Box, 1 Vial @ 1 g Gemhope, Reg No. : DKI2055000244A1
USE PRESCRIPTION ONLY
Manufactured by :
Glenmark Generics S.A
Calle 9, No. 593
Parque Industrial Pilar
Provincia de Buenos Aires
Republica Argentina
T +54 0230-4529555
Manufactured for :
Glenmark Pharmaceutical Ltd.
B/2, Mahalaxmi Chambers
22, Bhulabhai Desai Road
Mumbai – 400 026, India
Imported and distributed by :
Graha Farma
Solo – Indonesia
