Gemcitabine

Intravenous
Non-small cell lung cancer
Adult: Patient w/ locally advanced or metastatic cases: Monotherapy: 1,000 mg/m² once wkly via infusion over 30 min for 3 wk followed by 1 wk rest. This 4-wk cycle is then repeated. Combination therapy w/ cisplatin: 1,000 mg/m² via infusion over 30 min on days 1, 8, and 15 of a 28-day cycle. Alternatively, 1,250 mg/m² via infusion over 30 min on days 1 and 8 of a 21-day cycle. Dosage may reduce w/ each cycle or w/in a cycle based on toxicity.
Reconstitution: Add 5 or 25 mL of NaCl 0.9% inj in a vial labelled as containing 200 or 1,000 mg respectively, to provide a soln containing 38 mg/mL.

Intravenous
Pancreatic cancer
Adult: Patient w/ locally advanced or metastatic cases: 1,000 mg/m² once wkly via infusion over 30 min for 7 wk followed by 1 wk rest, then once wkly for 3 consecutive wk out of every 4 wk cycle. Dosage may reduce w/ each cycle or w/in a cycle based on toxicity.
Reconstitution: Add 5 or 25 mL of NaCl 0.9% inj in a vial labelled as containing 200 or 1,000 mg respectively, to provide a soln containing 38 mg/mL.

Intravenous
Bladder cancer
Adult: Patient w/ locally advanced or metastatic cases: Combination therapy w/ cisplatin: 1,000 mg/m² via infusion over 30 min on days 1, 8 and 15 of a 28-day cycle. This 4-wk cycle is then repeated. Dosage may reduce w/ each cycle or w/in a cycle based on toxicity.
Reconstitution: Add 5 or 25 mL of NaCl 0.9% inj in a vial labelled as containing 200 or 1,000 mg respectively, to provide a soln containing 38 mg/mL.

Intravenous
Breast cancer
Adult: Patient w/ unresectable, locally recurrent, or metastatic cases: Combination therapy w/ paclitaxel: 1,250 mg/m² via infusion over 30 min on days 1 and 8 of a 21-day cycle. Dosage may reduce w/ each cycle or w/in a cycle based on toxicity. Patients should have absolute granulocyte count of ≥1,500 x 10⁶/L prior to initiation of therapy.
Reconstitution: Add 5 or 25 mL of NaCl 0.9% inj in a vial labelled as containing 200 or 1,000 mg respectively, to provide a soln containing 38 mg/mL.

Intravenous
Ovarian cancer
Adult: Patient w/ locally advanced or metastatic epithelial cases: Combination therapy w/ carboplatin: 1,000 mg/m² via infusion over 30 min on days 1 and 8 of a 21-day cycle. Dosage may reduce w/ each cycle or w/in a cycle based on toxicity.
Reconstitution: Add 5 or 25 mL of NaCl 0.9% inj in a vial labelled as containing 200 or 1,000 mg respectively, to provide a soln containing 38 mg/mL.

Lactation. Admin of yellow fever and other live attenuated vaccines.

Patient w/ history of cirrhosis, hepatitis, alcoholism, CV events. Patients on radiotherapy. Hepatic (e.g. hepatic metastases) and renal impairment. Pregnancy. Prolonged infusion duration of >60 min or more frequent than wkly dosing may increase toxicity. Patient Counselling This drug may cause somnolence, if affected, do not drive or operate machinery. Monitoring Parameters Monitor CBC w/ differential and platelet count prior to each dose. Monitor pulmonary, hepatic, and renal function; electrolytes (i.e. K, Mg, Ca) when in combination therapy w/ cisplatin. Monitor for signs and symptoms of capillary leak syndrome and PRES.

Significant: Bone marrow suppression manifested by neutropenia, thrombocytopaenia, and anaemia; capillary leak syndrome, posterior reversible encephalopathy syndrome (PRES). Nervous: Somnolence, flu-like symptoms, paraesthesia. CV: Peripheral oedema. GI: Nausea, vomiting, diarrhea, stomatitis, constipation. Resp: Dyspnoea. Hepatic: Transient liver enzyme elevations (e.g. AST, ALT, bilirubin, alkaline phosphatase). Genitourinary: Haematuria, proteinuria, increased BUN. Haematologic: Haemorrhage. Musculoskeletal: Myalgia. Dermatologic: Rash, pruritus, oedema, thrombocytopenic purpura, alopecia, peripheral vasculitis, gangrene. Immunologic: Infection. Others: Pain, fever, extravasation, injection site reaction.
Potentially Fatal: Severe hepatotoxicity (e.g. liver failure), pulmonary toxicity (e.g. pulmonary oedema, pulmonary fibrosis, interstitial pneumonitis, adult resp distress syndrome), ischaemic colitis w/ necrosis. Rarely, haemolytic uremic syndrome leading to renal failure.

Symptoms: Myelosuppression, severe rash, paraesthesia. Management: Supportive treatment. Monitor CBC.

May cause pulmonary toxicity w/ concurrent use of bleomycin. May enhance anticoagulant effect of warfarin.
Potentially Fatal: Admin of yellow fever and other live attenuated vaccines may increase risk of systemic disease esp in immunosuppressed patients.

Gemcitabine, a synthetic pyrimidine nucleoside and cytarabine analogue, inhibits DNA synthesis by blocking DNA polymerase and ribonucleotide reductase. It is cell-cycle specific acting mainly on the S-phase, but may also block cellular progression at the G1-S border.
Distribution: Widely distributed into tissues; present in ascitic fluid. Volume of distribution: 50 L/m² (<70 min infusion time); 370 L/m² (70-285 min infusion time).
Metabolism: Rapidly metabolised in the liver, kidney, blood, and other tissues by cytidine deaminase to the inactive metabolite 2'-deoxy-2',2'-difluorouridine (dFdU); undergoes intracellular metabolism by nucleoside kinases to the active metabolites, gemcitabine diphosphate and triphosphate nucleosides.
Excretion: Mainly via urine (92-98% mainly as dFdU; <10% as unchanged drug) and faeces (<1% ). Elimination half-life: Gemcitabine: Approx 42-94 min (≤70 min infusion time); 4-10.5 hr (3-4 hr infusion time). Gemcitabine triphosphate: 1.7-19.4 hr.

Intravenous: Concentrate soln for infusion: Store between 2-8°C. Powder for soln for infusion: Store between 20-25°C. Avoid inhalation and contact w/ skin or mucous membranes by wearing gloves and protective equipments. Wash hands before and after handling. Any unused portions should be disposed of in accordance w/ local requirements. Pregnant staff should not handle this product.

Cytotoxic Chemotherapy

L01BC05 - gemcitabine ; Belongs to the class of antimetabolites, pyrimidine analogues. Used in the treatment of cancer.