Source: http://rxdrugsinfo.com/drug-info-label/ifex-mesnex
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IFEX®(ifosfamide for injection) - Drug label and information - Rx Drugs Info
ifex/mesnex (ifosfamide and mesna)
ifex (ifosfamide) injection, powder, for solution
IFEX should be administered under the supervision of a qualified physician experienced in the use of cancer chemotherapeutic agents. Urotoxic side effects, especially hemorrhagic cystitis, as well as CNS toxicities such as confusion and coma have been associated with the use of IFEX. When they occur, they may require cessation of IFEX therapy. Severe myelosuppression has been reported. (See ADVERSE REACTIONS section.)
IFEX should be given cautiously to patients with impaired renal function as well as to those with compromised bone marrow reserve, as indicated by: leukopenia, granulocytopenia, extensive bone marrow metastases, prior radiation therapy, or prior therapy with other cytotoxic agents.
Pregnancy “Category D.” (See WARNINGS section.)
In pregnant mice, resorptions increased and anomalies were present at day 19 after 30 mg/m2 dose of ifosfamide was administered on day 11 of gestation. Embryolethal effects were observed in rats following the administration of 54 mg/m2 doses of ifosfamide from the 6th through the 15th day of gestation and embryotoxic effects were apparent after dams received 18 mg/m2 doses over the same dosing period. Ifosfamide is embryotoxic to rabbits receiving 88 mg/m2/day doses from the 6th through the 18th day after mating. The number of anomalies was also significantly increased over the control group.
In patients receiving IFEX as a single agent, the dose-limiting toxicities are myelosuppression and urotoxicity. Dose fractionation, vigorous hydration, and a protector such as mesna can significantly reduce the incidence of hematuria, especially gross hematuria, associated with hemorrhagic cystitis. At a dose of 1.2 g/m2 daily for 5 consecutive days, leukopenia, when it occurs, is usually mild to moderate. Other significant side effects include alopecia, nausea, vomiting, and central nervous system toxicities.
Myelosuppression was dose related and dose limiting. It consisted mainly of leukopenia and, to a lesser extent, thrombocytopenia. A WBC count<3000/µL is expected in 50% of the patients treated with IFEX single agent at doses of 1.2 g/m2 per day for 5 consecutive days. At this dose level, thrombocytopenia (platelets <100,000/µL) occurred in about 20% of the patients. At higher dosages, leukopenia was almost universal, and at total dosages of 10-12 g/m2/cycle, one half of the patients had a WBC count below 1000/µL and 8% of patients had platelet counts less than 50,000/µL. Myelosuppression was usually reversible and treatment can be given every 3 to 4 weeks. When IFEX is used in combination with other myelosuppressive agents, adjustments in dosing may be necessary. Patients who experience severe myelosuppression are potentially at increased risk for infection. Anemia has been reported as part of postmarketing surveillance.
Nausea and vomiting occurred in 58% of the patients who received IFEX. They were usually controlled by standard antiemetic therapy. Other gastrointestinal side effects include anorexia, diarrhea, and in some cases, constipation.
Urotoxicity consisted of hemorrhagic cystitis, dysuria, urinary frequency and other symptoms of bladder irritation. Hematuria occurred in 6% to 92% of patients treated with IFEX. The incidence and severity of hematuria can be significantly reduced by using vigorous hydration, a fractionated dose schedule and a protector such as mesna. At daily doses of 1.2 g/m2 for 5 consecutive days without a protector, microscopic hematuria is expected in about one half of the patients and gross hematuria in about 8% of patients.
Renal toxicity occurred in 6% of the patients treated with ifosfamide as a single agent. Clinical signs, such as elevation in BUN or serum creatinine or decrease in creatinine clearance, were usually transient. They were most likely to be related to tubular damage. One episode of renal tubular acidosis which progressed into chronic renal failure was reported. Proteinuria and acidosis also occurred in rare instances. Metabolic acidosis was reported in 31% of patients in one study when IFEX was administered at doses of 2.0 to 2.5 g/m2/day for 4 days. Renal tubular acidosis, Fanconi syndrome, renal rickets, and acute renal failure have been reported. Close clinical monitoring of serum and urine chemistries including phosphorus, potassium, alkaline phosphatase and other appropriate laboratory studies is recommended. Appropriate replacement therapy should be administered as indicated.
CNS side effects were observed in 12% of patients treated with IFEX. Those most commonly seen were somnolence, confusion, depressive psychosis, and hallucinations. Other less frequent symptoms include dizziness, disorientation, and cranial nerve dysfunction. Seizures and coma with death were occasionally reported. The incidence of CNS toxicity may be higher in patients with altered renal function.
Alopecia occurred in approximately 83% of the patients treated with IFEX as a single agent. In combination, this incidence may be as high as 100%, depending on the other agents included in the chemotherapy regimen. Increases in liver enzymes and/or bilirubin were noted in 3% of the patients. Other less frequent side effects included phlebitis, pulmonary symptoms, fever of unknown origin, allergic reactions, stomatitis, cardiotoxicity, and polyneuropathy.
No specific antidote for IFEX is known. Management of overdosage would include general supportive measures to sustain the patient through any period of toxicity that might occur.
IFEX should be administered intravenously at a dose of 1.2 g/m2 per day for 5 consecutive days. Treatment is repeated every 3 weeks or after recovery from hematologic toxicity (Platelets ≥100,000/µL, WBC ≥4,000/µL). In order to prevent bladder toxicity, IFEX should be given with extensive hydration consisting of at least 2 liters of oral or intravenous fluid per day. A protector, such as mesna, should also be used to prevent hemorrhagic cystitis. IFEX should be administered as a slow intravenous infusion lasting a minimum of 30 minutes. Although IFEX has been administered to a small number of patients with compromised hepatic and/or renal function, studies to establish optimal dose schedules of IFEX in such patients have not been conducted.
Because essentially identical stability results were obtained for Sterile Water admixtures as for the other admixtures (5% Dextrose Injection, 0.9% Sodium Chloride Injection, and Lactated Ringer’s Injection), the use of large volume parenteral glass bottles, Viaflex bags or PAB™ bags that contain intermediate concentrations or mixtures of excipients (eg, 2.5% Dextrose Injection, 0.45% Sodium Chloride Injection, or 5% Dextrose and 0.9% Sodium Chloride Injection) is also acceptable.
IFEX® (ifosfamide for injection) is available in combination packages with the uroprotective agent Mesnex® (mesna) injection or as single-dose vials as follows:
IFEX (ifosfamide for injection)/Mesnex (mesna) injection.
NDC 0015-3556-26 5 × 1-gram Single-Dose Vial of Ifex/3 × 1-gram Multidose Vial of Mesnex
NDC 0015-3554-27 10 × 1-gram Single-Dose Vial of Ifex/10 × 1-gram Multidose Vial of Mesnex
NDC 0015-3564-15 2 × 3-gram Single-Dose Vial of Ifex/6 × 1-gram Multidose Vial of Mesnex
NDC 0015-0556-05 1-gram Single-Dose Vial
NDC 0015-0557-41 3-gram Single-Dose Vial
Store at controlled room temperature 20° C to 25° C (68° F to 77° F).
Protect from temperatures above 30° C (86° F).
Clinical Oncological Society of Australia: Guidelines and Recommendations for Safe Handling of Antineoplastic Agents. Med J Australia 1983;1:426-428.
1029940A5
USA 5663-7004 C 470
Rev Jul 2007
Product Code 0015-3556 Dosage Form KIT
1 0015-3556-26 1 KIT In 1 PACKAGE, COMBINATION None
Part 1 5 VIAL, SINGLE-DOSE 100 MILLILITER In 1
Part 2 3 VIAL, MULTI-DOSE 30 MILLILITER In 1
Route Of Administration INTRAVENOUS Dosage Form INJECTION, POWDER, FOR SOLUTION
ifosfamide (ifosfamide) Active 1 GRAM In 20 MILLILITER
1 1 VIAL In 1 CARTON contains a VIAL, SINGLE-DOSE
1 20 MILLILITER In 1 VIAL, SINGLE-DOSE This package is contained within the CARTON
benzyl alcohol Inactive 10.4 MILLIGRAM In 1 MILLILITER
1 1 VIAL In 1 CARTON contains a VIAL, MULTI-DOSE
1 10 MILLILITER In 1 VIAL, MULTI-DOSE This package is contained within the CARTON
Product Code 0015-3554 Dosage Form KIT
1 0015-3554-27 1 KIT In 1 PACKAGE, COMBINATION None
Part 1 10 VIAL, SINGLE-DOSE 200 MILLILITER In 1
Part 2 10 VIAL, MULTI-DOSE 100 MILLILITER In 1
Product Code 0015-3564 Dosage Form KIT
1 0015-3564-15 1 KIT In 1 PACKAGE, COMBINATION None
Part 1 2 VIAL, SINGLE-DOSE 120 MILLILITER In 1
Part 2 6 VIAL, MULTI-DOSE 60 MILLILITER In 1
ifosfamide (ifosfamide) Active 3 GRAM In 60 MILLILITER
1 60 MILLILITER In 1 VIAL, SINGLE-DOSE This package is contained within the CARTON
Product Code 0015-0556 Dosage Form INJECTION, POWDER, FOR SOLUTION
1 0015-0556-05 1 VIAL In 1 CARTON contains a VIAL, SINGLE-DOSE
1 20 MILLILITER In 1 VIAL, SINGLE-DOSE This package is contained within the CARTON (0015-0556-05)
Product Code 0015-0557 Dosage Form INJECTION, POWDER, FOR SOLUTION
1 0015-0557-41 1 VIAL In 1 CARTON contains a VIAL, SINGLE-DOSE
1 60 MILLILITER In 1 VIAL, SINGLE-DOSE This package is contained within the CARTON (0015-0557-41)