avenous injection,perhaps due to a direct effect of Cremophor EL.If clinically significant hypotension develops, the VUMON infusion shouldbe discontinued. The blood pressure usually normalizes within hours in responseto cessation of the infusion and administration of fluids or other supportivetherapy as appropriate. If the infusion is restarted, a slower administrationrate should be used and the patient should be carefully monitored.
Acute central nervous system depression, hypotension, and metabolic acidosis have beenobserved in patients receiving investigational infusions of high-dose VUMONwho were pretreated with antiemetic drugs. The depressant effects of the antiemeticagents and the alcohol content of the VUMON formulation may place patientsreceiving higher than recommended doses of VUMON at risk for central nervoussystem depression.
VUMON may cause fetal harm when administeredto a pregnant woman. VUMON has been shown to be teratogenic and embryotoxicin laboratory animals. In pregnant rats, intravenous administration of VUMON,0.1 to 3 mg/kg (0.6-18 mg/m), every second dayfrom day 6 to day 16 post coitum caused dose-related embryotoxicity and teratogenicity.Major anomalies included spinal and rib defects, deformed extremities, anophthalmia,and celosomia.
There are no adequate and well-controlledstudies in pregnant women. If VUMON is used during pregnancy, or if the patientbecomes pregnant while receiving this drug, the patient should be apprisedof the potential hazard to the fetus. Women of childbearing potential shouldbe advised to avoid becoming pregnant during therapy with VUMON.
In all instances where the use of VUMON is considered for chemotherapy,the physician must eva luate the need and usefulness of the drug against therisk of adverse reactions. Most such adverse reactions are reversible if detectedearly. If severe reactions occur, the drug should be reduced in dosage ordiscontinued and appropriate corrective measures should be taken accordingto the clinical judgment of the physician. Reinstitution of VUMON therapyshould be carried out with caution, and with adequate consideration of thefurther need for the drug and alertness as to possible recurrence of toxicity.
VUMON must be administered as an intravenous infusion. Care shouldbe taken to ensure that the intravenous catheter or needle is in the properposition and functional prior to infusion. Improper administration of VUMONmay result in extravasation causing local tissue necrosis and/or thrombophlebitis.In some instances, occlusion of central venous access devices has occurredduring 24-hour infusion of VUMON at a concentration of 0.1 to 0.2 mg/mL. Frequentobservation during these infusions is necessary to minimize this risk.
Periodic complete blood counts and assessments of renal and hepaticfunction should be done during the course of VUMON treatment. They shouldbe performed prior to therapy and at clinically appropriate intervals duringand after therapy. There should be at least one determination of hematologicstatus prior to therapy with VUMON.
In a study in which 34 different drugs were tested, therapeuticallyrelevant concentrations of tolbutamide, sodium salicylate, and sulfamethizoledisplaced protein-bound teniposide in fresh human serum to a small but significantextent. Because of the extremely high binding of teniposide to plasma proteins,these small decreases in binding could cause substantial increases in
