Gemcitabine Hcl (gemcitabine HCl)

Dosage of gemcitabine hydrochloride is expressed in terms of gemcitabine and must be individualized based on body surface area and patient tolerance and response.

The manufacturer warns that gemcitabine should not be administered more frequently than once weekly since the risk of toxicity is increased with such dosing. In a phase 1 trial designed to assess the maximum tolerated dose on a schedule of 5 consecutive daily doses, patients developed intolerable hypotension and flu-like symptoms at gemcitabine dosages exceeding 10 mg/m2 daily; the incidence and severity of these effects were dose related. In other dose-ranging phase 1 trials using twice-weekly schedules, maximum tolerated gemcitabine doses were 65 mg/m2 when the drug was infused over 30 minutes and 150 mg/m2 when the drug was injected over 5 minutes; in these trials, dose-limiting toxicities included thrombocytopenia and flu-like symptoms, particularly asthenia.

Although optimum dosage regimens have not been established, gemcitabine dosages of 1 or 1.25 g/m2 administered by 30-minute IV infusion once weekly for 3 weeks followed by 1 week of rest have been used most commonly in patients receiving gemcitabine as monotherapy for advanced non-small cell lung cancer. Various dosage schedules have been studied for the combination of gemcitabine with cisplatin for the treatment of advanced non-small cell lung cancer; gemcitabine dosages of 1 g/m2 administered once weekly for 3 weeks on a 4-week cycle or 1.25 g/m2 administered once weekly for 2 weeks on a 3-week cycle have been used in large randomized trials (see Dosage and Administration: Dosage); gemcitabine doses of 1-1.5 g/m2 have been used in combination with cisplatin in phase 2 studies. Other dosage schedules for gemcitabine (e.g., higher doses, lower doses administered over longer infusion periods) are being investigated in patients with advanced non-small cell lung cancer.

Further study is needed to define the role of gemcitabine used alone or in combination therapy for the treatment of advanced non-small cell lung cancer. No single chemotherapy regimen currently can be recommended as superior in the treatment of non-small cell lung cancer. Various chemotherapy regimens used alone or in combination with other treatment modalities, such as radiation therapy, are continually being evaluated for the treatment of advanced non-small cell lung cancer. Because current treatment is not satisfactory for almost all patients with non-small cell lung cancer except selected patients with early-stage, resectable disease, all patients may be considered for enrollment in clinical trials at the time of diagnosis.

Dosage escalation can be considered for patients with pancreatic cancer who successfully complete the initial 7-week or subsequent 3-week cycle of gemcitabine therapy at the full weekly dosage of 1 g/m2, provided nadirs of the absolute granulocyte and platelet counts exceed 1500 and 100,000/mm3, respectively, and nonhematologic toxicity exceeding a World Health Organization (WHO) grade of 1 is not present. In such patients, the dosage can be increased to 1.25 g/m2 weekly. If a complete 3-week course at a dosage of 1.25 g/m2 is tolerated (i.e., these hematologic parameters are met and there is no evidence of WHO grade 1 nonhematologic toxicity), dosage can be escalated further to 1.5 g/m2 weekly given in 3-week cycles.

No dosing information is available for this tab.

No dosing information is available for this tab.

No dosing information is available for this tab.

No formal drug interaction studies have been performed to date.

There are no contraindication interactions for this drug.

There are no severe interactions for this drug.

There are no moderate interactions for this drug.

Known hypersensitivity to gemcitabine or any ingredient in the formulation.

There are no contraindication contraindications for this drug.

There are no severe contraindications for this drug.

There are no moderate contraindications for this drug.

Adverse effects reported in 10% or more of patients receiving gemcitabine monotherapy include myelosuppression (i.e., anemia, leukopenia, neutropenia, thrombocytopenia), proteinuria, hematuria, increased BUN, nausea, vomiting, pain, fever, rash, pruritus, dyspnea, constipation, diarrhea, hemorrhage, peripheral edema, edema, flu-like symptoms, infection, alopecia, stomatitis, somnolence, paresthesias, and increased serum AST, ALT, alkaline phosphatase, and bilirubin concentrations.

There are no severe adverse reactions for this drug.

There are no less severe adverse reactions for this drug.

No enhanced messaging available.

Efficacy of gemcitabine has not been established in children younger than 18 years of age. In a phase 1 study in pediatric patients with refractory leukemia+, the maximum tolerated dosage of gemcitabine was 10 mg/m2 per minute for 6 hours (360 minutes) 3 times weekly, followed by 1 week of rest. When gemcitabine was administered at this dosage in a phase 2 study in patients with relapsed acute lymphoblastic leukemia+ or acute myelogenous leukemia+, no clinically important activity was observed. Adverse effects reported in these studies were similar to those reported in adults and included bone marrow suppression, febrile neutropenia, increased serum transaminases, nausea, and rash/desquamation.

Category D. (See Fetal/Neonatal Morbidity and Mortality under Warnings/Precautions: Warnings, in Cautions.) (See Users Guide.)

It is not known whether gemcitabine is distributed into milk. The manufacturer states that a decision should be made whether to discontinue nursing or the drug, taking into account the importance of the drug to the woman and the potential risk to nursing infants..

Because gemcitabine clearance is reduced and half-life is increased in geriatric patients, dosage reductions, including withholding of doses in some cases, may be more likely in this population; however, there currently is no evidence that unusual dosage adjustments (i.e., other than those recommended in general for hematologic and nonhematologic toxicity) would be required. Information derived from the safety database for gemcitabine monotherapy indicates that the frequency of adverse effects in patients older than 65 years of age is similar to that in younger adults; however, severe (grade 3/4) thrombocytopenia has occurred more frequently in geriatric patients. In the clinical study of gemcitabine given in combination with carboplatin for recurrent ovarian cancer, no overall differences in efficacy or safety were observed between geriatric and younger patients; however, grade 3/4 neutropenia occurred more frequently in geriatric patients 65 years of age or older.