m), on days 6 through 15 of gestation. Fetal malformations that were observed were an omphalocele at 0.05 mg/kg (0.3 mg/m), gastroschisis at 0.75 mg/kg and 1 mg/kg (4.5 and 6 mg/m), and a flexure defect of the hindlimbs at 0.75 mg/kg (4.5 mg/m). Pentostatin was also shown to be teratogenic in mice when administered as a single 2 mg/kg (6 mg/m) intraperitoneal injection on day 7 of gestation. Pentostatin was not teratogenic in rabbits when administered intravenously on days 6 through 18 of gestation at doses of 0, 0.005, 0.01, or 0.02 mg/kg/day (0, 0.015, 0.03, or 0.06 mg/m); however maternal toxicity, abortions, early deliveries, and deaths occurred in all drug-treated groups. There are no adequate and well-controlled studies in pregnant women. If NIPENT is used during pregnancy, or if the patient becomes pregnant while taking (receiving) this drug, the patient should be apprised of the potential hazard to the fetus. Women of childbearing potential receiving NIPENT should be advised to avoid becoming pregnant.
Therapy with NIPENT requires regular patient observation and monitoring of hematologic parameters and blood chemistry values. If severe adverse reactions occur, the drug should be withheld (see DOSAGE AND ADMINISTRATION ), and appropriate corrective measures should be taken according to the clinical judgment of the physician.
NIPENT treatment should be withheld or discontinued in patients showing evidence of nervous system toxicity.
Patients should be advised of the signs and symptoms of adverse events associated with NIPENT therapy. (See ADVERSE REACTIONS .)
Prior to initiating therapy with NIPENT, renal function should be assessed with a serum creatinine and/or a creatinine clearance assay. (See CLINICAL PHARMACOLOGY and DOSAGE AND ADMINISTRATION .) Complete blood counts and serum creatinine should be performed before each dose of NIPENT and at other appropriate periods during therapy (see DOSAGE AND ADMINISTRATION ). Severe neutropenia has been observed following the early courses of treatment with NIPENT and therefore frequent monitoring of complete blood counts is recommended during this time. If hematologic parameters do not improve with subsequent courses, patients should be eva luated for disease status, including a bone marrow examination. Periodic monitoring of the peripheral blood for hairy cells should be performed to assess the response to treatment.
In addition, bone marrow aspirates and biopsies may be required at 2 to 3 month intervals to assess the response to treatment.
Allopurinol and NIPENT are both associated with skin rashes. Based on clinical studies in 25 refractory patients who received both NIPENT and allopurinol, the combined use of NIPENT and allopurinol did not appear to produce a higher incidence of skin rashes than observed with NIPENT alone. There has been a report of one patient who received both drugs and experienced a hypersensitivity vasculitis that resulted in death. It was unclear whether this adverse event and subsequent death resulted from the drug combination.
Biochemical studies have demonstrated that pentostatin enhances the effects of vidarabine, a purine nucleoside with antiviral activity. The combined use of vidarabine and NIPENT may result in an increase in adverse reactions associated with each drug. The therapeutic benefit of the drug combination has not been established.
The combined use of NIPENT and fludarabine phosphate is not recommended because it may be associated with
