Caution should be used when administering ibuprofen concurrently with ALIMTA to patients with mild to moderate renal insufficiency (creatinine clearance from 45 to 79 mL/min). Patients with mild to moderate renal insufficiency should avoid taking NSAIDs with short elimination half-lives for a period of 2 days before, the day of, and 2 days following administration of ALIMTA. In the absence of data regarding potential interaction between ALIMTA and NSAIDs with longer half-lives, all patients taking these NSAIDs should interrupt dosing for at least 5 days before, the day of, and 2 days following ALIMTA administration. If concomitant administration of an NSAID is necessary, patients should be monitored closely for toxicity, especially myelosuppression, renal and gastrointestinal toxicities.
Concomitant administration of nephrotoxic drugs or substances that are tubularly secreted could result in delayed clearance of ALIMTA.
It is recommended that nursing be discontinued if the mother is being treated with ALIMTA.
ALIMTA should be administered under the supervision of a qualified physician experienced in the use of antineoplastic agents.
Dose adjustments may be necessary in patients with hepatic insufficiency.
Dosing and Modification Guidelines
Dose adjustments at the start of a subsequent cycle should be based on nadir hematologic counts or maximum nonhematologic toxicity from the preceding cycle of therapy. Modify or suspend therapy according to the Dosage Reduction Guidelines in the full Prescribing Information.
Adverse Events
The most common adverse events (grades 3/4) with ALIMTA in combination with cisplatin for the treatment of patients with MPM were neutropenia (24%); leukopenia (16%); anemia (6%); thrombocytopenia (5%); infection without neutropenia (2%); fatigue (17%); thrombsis/embolism (6%); nausea (12%); vomiting (11%); dyspnea (11%); and chest pain (9%). The most common clinically relevant adverse events (all grades) were fatigue (80%); thrombosis/embolism (7%); nausea (84%); vomiting (58%); constipation (44%); anorexia (35%); stomatitis/pharyngitis (28%); diarrhea (26%); dyspnea (66%); chest pain (40%); and rash (22%).
The most common adverse events (grades 3/4) with ALIMTA for the treatment of patients with NSCLC were anemia (8%); leukopenia (5%); neutropenia (5%); thrombocytopenia (2%); infection without neutropenia (6%); fatigue (16%); thrombosis/embolism (3%); cardiac ischemia (3%);anorexia (5%); dyspnea (18%); and chest pain (7%). The most common clinically relevant adverse events (all grades) were fatigue (87%); anorexia (62%); nausea (39%); constipation (30%); vomiting (25%); diarrhea (21%); stomatitis/pharyngitis (20%); dyspnea (72%); chest pain (38%); neuropathy/sensory (29%); infection without neutropenia (23%); and rash (17%).
See complete Warnings, Precautions, Adverse Reactions, and Dosage and Administration sections in the accompanying full Prescribing Information for safety and dosing guidelines.
GEMZAR
Indications
GEMZAR in combination with paclitaxel is indicated for the first-line treatment of patients with metastatic breast cancer after failure of prior anthracycline-containing adjuvant chemotherapy, unless anthracyclines were clinically contraindicated.
GEMZAR is indicated in combination with cisplatin for the first-line treatment of patients with inoperable, locally advanced (stage IIIA or IIIB), or metastatic (stage IV) non-small cell lung cancer.
GEMZAR is indicated as first-line treatment for patients with locally advanced (nonresectable stage II or stage III) or metastatic (stage IV)adenocarcinoma of the pancreas. GEMZAR is indicated for patients previously treated with 5-FU.
GEMZAR in combination with carboplatin is indicated for the treatment of patients with advanced ovarian cancer that has relapsed at least 6 months after completion of platinum-based therapy.
Important Safety Information for GEMZAR
Myelosuppression is usually the dose-limiting toxicity with GEMZAR therapy.
Contraindication
Known hypersensitivity to GEMZAR. Anaphylactoid reaction has been reported rarely.
Warnings
Infusion times of GEMZAR longer than 60 minutes and more frequent than weekly dosing have been shown to increase toxicity.
Pulmonary toxicity has been reported with the use of GEMZAR. In cases of severe lung toxicity, GEMZAR therapy should be discontinued immediately and appropriate supportive care measures instituted.
Hemolytic Uremic Syndrome (HUS) and/or renal failure have been reported following one or more doses of GEMZAR. Renal failure leading to death or requiring dialysis, despite discontinuation of therapy, has been rarely reported. The majority of the cases of renal failure leading to death were due to HUS.
Serious hepatotoxicity, including liver failure and death, has been reported very rarely in patients receiving GEMZAR alone or in combination with other potentially hepatotoxic drugs.
GEMZAR is Pregnancy Category D. GEMZAR can cause fetal harm when administered to a pregnant woman.
Precautions
Use caution in patients with pre-existing renal impairment or hepatic insufficiency. Administration of GEMZAR may exacerbate underlying hepatic insufficiency.
The optimum regimen for safe administration of GEMZAR with therapeutic doses of radiation has not yet been determined in all tumor types. GEMZAR has radiosensitizing activity and radiation recall reactions have been reported.
It is not known whether GEMZAR or its metabolites are excreted in human milk.
The effectiveness of GEMZAR in pediatric patients has not been demonstrated.
The toxicities of GEMZAR observed in pediatric patients were similar to those reported in adults.
GEMZAR clearance is affected by age as well as gender.
Patients receiving therapy with GEMZAR should be monitored closely by a physician experienced in the use of cancer chemotherapeutic agents.
Monitoring and Dosage Modifications
Dosage adjustments for hematologic toxicity may be required.
Serum creatinine, potassium, calcium, and magnesium should be monitored during combination therapy with cisplatin.
Patients should be assessed with a CBC, including differential and platelet count, prior to each dose of GEMZAR. Modify or suspend therapy according to the Dosage Reduction Guidelines in the full Prescribing Information.
Hepatic and renal function (including transaminases and serum creatinine) should be evaluated prior to therapy with GEMZAR and periodically thereafter.
Adverse Events
The most severe adverse events (grades 3/4) with GEMZAR plus paclitaxel for the treatment of patients with MBC were neutropenia (48%); alopecia (18%); leukopenia (11%); anemia (7%); fatigue (7%); thrombocytopenia (6%); ALT elevation (6%); and neuropathy-sensory (6%). The most common adverse events (all grades) were nausea (50%); fatigue (40%); myalgia (33%); and vomiting (29%).
The most severe adverse events (grades 3/4) with GEMZAR for the first-line treatment of patients with pancreatic cancer were neutropenia (24%-26%); alkaline phosphatase elevation (16%-20%); AST elevation (12%-17%); nausea/vomiting (12%-13%); ALT elevation (10%-11%); anemia (10%); leukopenia (9%-10%); thrombocytopenia (8%-10%); bilirubin elevation (4%-8%); and pain (2%-7%). The most common adverse events (all grades) were AST (72%-78%); alkaline phosphatase (71%-77%); anemia (65%-73%); ALT (72%); leukopenia (64%-71%); nausea and vomiting (64%-71%); neutropenia (61%-62%); thrombocytopenia (36%-47%); pain (10%-42%); fever (30%-38%); proteinuria (10%-32%); constipation (10%-31%); diarrhea (24%-30%); rash (24%-28%); and bilirubin (16%-26%).
The most severe adverse events (grades 3/4) with GEMZAR plus cisplatin for the first-line treatment of patients with NSCLC were neutropenia (57%-64%); thrombocytopenia (50%-55%); leukopenia (29%-46%); anemia (22%-25%); nausea (27%); vomiting (23%); nausea/vomiting (39%); neuromotor (12%); hypomagnesemia (7%); neurohearing (6%); creatinine elevation (5%); alopecia (1%-13%); and dyspnea (1%-7%). The most common adverse events (all grades) were paresthesias (38%); hyperglycemia (30%); infection (18%-28%); and constipation (17%-28%).
(CONTINUA)
