Gemcitabine is used to treat several types of cancer, either alone or in combination with other anticancer medicines.

Non-Small Cell Lung Cancer (NSCLC): Gemcitabine combined with Cisplatin is used as a first-line treatment for patients with locally advanced (inoperable Stage IIIA or IIIB) or metastatic (Stage IV) non-small cell lung cancer. It may also be used for palliative treatment in adults with advanced or metastatic NSCLC.

Pancreatic Cancer: Gemcitabine is indicated for adults with locally advanced or metastatic pancreatic adenocarcinoma. It is also used in patients whose pancreatic cancer does not respond to previous treatment with Fluorouracil (5-FU).

Bladder Cancer: Gemcitabine, in combination with Cisplatin, is used to treat advanced bladder cancer, including muscle-invasive Stage IV tumors with or without metastasis.

Breast Cancer: Gemcitabine together with Paclitaxel is used to treat metastatic breast cancer in patients whose disease has returned after adjuvant or neoadjuvant chemotherapy. Previous treatment usually included an anthracycline, unless it was medically unsuitable.

Ovarian Cancer: Gemcitabine combined with Carboplatin is used for patients with recurrent epithelial ovarian cancer that has relapsed after platinum-based chemotherapy.

Gemcitabine (dFdC) is converted inside cells by nucleoside kinases into its active diphosphate (dFdCDP) and triphosphate (dFdCTP) forms. Its cytotoxic effect mainly results from inhibition of DNA synthesis through the actions of these metabolites. Firstly, dFdCDP inhibits ribonucleotide reductase, an enzyme responsible for producing deoxynucleoside triphosphates required for DNA synthesis. This leads to a reduction in intracellular deoxynucleotide levels, particularly dCTP. Secondly, dFdCTP competes with dCTP for incorporation into DNA. A small amount may also be incorporated into RNA. The decreased availability of dCTP enhances the incorporation of dFdCTP into DNA (self-potentiation). Once incorporated, DNA polymerase is unable to effectively remove gemcitabine, resulting in impaired DNA repair. After one additional nucleotide is added, DNA synthesis is effectively terminated (masked chain termination). Ultimately, incorporation of gemcitabine into DNA leads to inhibition of DNA replication and triggers programmed cell death (apoptosis).

Non-Small Cell Lung Cancer:
Single-agent Use: The recommended dose of Gemcitabine is 1000 mg/m², 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.

Combination Use: Gemcitabine, in combination with Cisplatin has been investigated using two dosing regimens. One regimen used a three-week schedule and the other used a four-week schedule. The three-week schedule used Gemcitabine 1250 mg/m², given by 30-minute intravenous infusion, on days 1 and 8 of each 21-day cycle. Dosage reduction with each cycle or within a cycle may be applied based upon the amount of toxicity experienced by the patient. The four-week schedule used Gemcitabine 1000 mg/m², given by 30-minute intravenous infusion, on days 1, 8, and 15 of each 28-day cycle. Dosage reduction with each cycle or within a cycle may be applied based upon the amount of toxicity experienced by the patient.

Pancreatic Cancer: The recommended dose of Gemcitabine is 1000 mg/m², 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:
Single agent use: The recommended dose of Gemcitabine is 1250 mg/m², given by 30-minute intravenous infusion. The dose should be given on days 1, 8 and 15 of each 28-day cycle. This 4-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: The recommended dose for Gemcitabine is 1000 mg/m², 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/m² on day 1 following Gemcitabine or day 2 of each 28-day cycle. This 4-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/m².

Breast Cancer: Gemcitabine in combination with Paclitaxel is recommended using Paclitaxel (175 mg/m²) administered on Day 1 over approximately 3 hours as an intravenous infusion, followed by Gemcitabine (1250 mg/m²) 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 (×10⁶/L) prior to initiation of Gemcitabine + Paclitaxel combination.

Ovarian Cancer: Gemcitabine in combination with Carboplatin is recommended using Gemcitabine 1000 mg/m² administered on days 1 and 8 of each 21-day cycle as a 30-minute intravenous infusion. After Gemcitabine, Carboplatin should be given on day 1 consistent with target AUC of 4.0 mg/mL/min. Dosage reduction with each cycle or within a cycle may be applied based upon the amount of toxicity experienced by the patient.

Gemcitabine currently has no well-established drug–drug interactions. Specific clinical studies evaluating interactions with other medicines have not been conducted.

Gemcitabine should not be used in patients who have a known hypersensitivity or allergy to Gemcitabine or any of the components of this medicine.

Hematological Toxicity: Since Gemcitabine suppresses bone marrow function, anemia, leukopenia, and thrombocytopenia may occur following its administration. Myelosuppression is generally mild to moderate and is more pronounced in granulocyte counts. Approximately two-thirds of patients experience some degree of anemia, although only 7% show hemoglobin levels below 8 g/100 mL. While 19% of patients required transfusions, only 0.2% discontinued treatment due to anemia. White blood cell counts are reduced in 61% of patients, but only 9% fall below 2000 cells/mm³ and only 0.1% discontinue due to leukopenia. Granulocyte counts decrease in 64% of patients, with nearly 25% dropping below 1000 cells/mm³. Platelet counts decrease in 21% of patients, but only 5% fall below 50,000 cells/mm³ and only 0.4% discontinue due to thrombocytopenia. Prior cytotoxic therapy increases the risk and severity of leukopenia, granulocytopenia, and thrombocytopenia. No cumulative hematological toxicity has been observed. Anemia can be managed with transfusions, while dose reduction or omission may be necessary in severe leukopenia or thrombocytopenia. Rare hemorrhagic events associated with thrombocytopenia have been reported but are usually disease-related. Thrombocythemia has also been reported (7.5%), but did not lead to treatment discontinuation. Febrile neutropenia is also commonly observed.

Hepatic Toxicity: Elevations in liver transaminase enzymes occur in about two-thirds of patients but are usually mild, non-progressive, and rarely require treatment discontinuation. Fewer than 10% of patients show elevations greater than five times the normal value, and only 0.5% discontinue due to liver abnormalities. In rare cases, liver failure has been reported, though confounded by other factors such as chronic alcohol use. ALT levels tend to decline over time even with continued therapy. Elevated alkaline phosphatase levels (>5× normal) occur in 6.6% of patients and may be related to bone disorders. Elevated bilirubin (>5× normal) occurs in 1.5% of patients, while most patients maintain normal bilirubin levels.

Gastrointestinal: Nausea, with or without vomiting, is reported in about one-third of patients. Around 20% require treatment for these symptoms, which are rarely dose-limiting and can be controlled with antiemetics. Only 0.9% of patients experience severe vomiting or discontinue therapy due to nausea and vomiting. Diarrhea and stomatitis are also common. Diarrhea is reported in 7% of patients and is generally mild, while only 0.5% experience severe diarrhea requiring treatment. No discontinuations due to diarrhea have been reported.

Genito-Urinary Toxicity: Mild proteinuria and hematuria occur in approximately half of the patients but are usually not clinically significant and do not typically affect serum creatinine or blood urea nitrogen levels. However, rare cases (0.6%) of renal failure have been reported, so caution is advised in patients with renal impairment. Rare instances (0.4%) of possible hemolytic uremic syndrome have also been noted. No cumulative renal toxicity has been observed.

Pulmonary Toxicity: Dyspnea occurring shortly after Gemcitabine administration is reported in about 10% of patients. It is usually mild, short-lived, and resolves without treatment. The exact mechanism is unclear. Only 0.6% of patients discontinue therapy due to dyspnea, and very few cases are directly attributed to the drug. Interstitial pneumonitis has been reported rarely.

Allergic Toxicity: Skin rash occurs in approximately 25% of patients, often accompanied by itching in about 10%. These reactions are generally mild and respond to local treatment. Rare cases of desquamation, vesiculation, and ulceration have been reported. Discontinuation due to skin toxicity is rare (0.3%). Gemcitabine is generally well tolerated during infusion, with minimal injection site reactions reported and no evidence of vesicant properties. Bronchospasm may occur but is usually mild and transient. The drug should not be used in patients with known hypersensitivity.

Neurotoxicity: Mild to moderate drowsiness occurs in about 10% of patients, with very few discontinuations (0.1%). Asthenia is commonly reported, sometimes with flu-like symptoms, and leads to discontinuation in about 1.4% of cases. Paresthesia occurs in 3.4% of patients but is severe in only 0.2%. Peripheral edema is reported in approximately 30% of patients and is usually mild to moderate and reversible after discontinuation. Rare cases of pulmonary edema (1%) and facial edema have also been observed.

Alopecia: Most patients (86.7%) do not experience hair loss. Mild to moderate alopecia occurs in about 13% of patients, while complete but reversible hair loss is rare (0.5%).

Gemcitabine is classified as Pregnancy Category D, meaning it may cause harm to the fetus. It is unknown whether Gemcitabine passes into breast milk, so breastfeeding during treatment is not recommended.

Gemcitabine should be used with caution in patients who are at risk of schedule-dependent toxicity, bone marrow suppression, pulmonary toxicity and respiratory failure, hemolytic uremic syndrome, liver toxicity, embryo-fetal toxicity, radiation-related toxicity, and potential impairment of fertility.

Elderly Patients: Gemcitabine is generally well tolerated in patients over 65 years. Dose adjustment is usually not required.

Renal & Hepatic Impairment: Use cautiously in patients with kidney or liver impairment, as clinical data are limited.

Children: Clinical studies in children are limited, and the safety and effectiveness of Gemcitabine in pediatric patients have not been clearly established.

There is no specific antidote for Gemcitabine overdose. Symptoms may include severe bone marrow suppression, paresthesia, and severe skin rash. In case of overdose, patients should receive supportive treatment and close monitoring.

Cytotoxic Chemotherapy

Store the vial in the original carton at 20°–25°C, protected from light. Do not refrigerate, as crystallization may occur. Keep out of the reach of children.