(pentostatin for injection)
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 CLcr 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 evaluated 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 an increased risk of fatal pulmonary toxicity (see WARNINGS).
Acute pulmonary edema and hypotension, leading to death, have been reported in the literature in patients treated with pentostatin in combination with carmustine, etoposide and high dose cyclophosphamide as part of the ablative regimen for bone marrow transplant.
Carcinogenesis: No animal carcinogenicity studies have been conducted with pentostatin.
Mutagenesis: Pentostatin was nonmutagenic when tested in Salmonella typhimurium strains TA-98, TA-1535, TA-1537, and TA-1538. When tested with strain TA-100, a repeatable statistically significant response trend was observed with and without metabolic activation. The response was 2.1 to 2.2 fold higher than the background at 10 mg/plate, the maximum possible drug concentration. Formulated pentostatin was clastogenic in the in vivo mouse bone marrow micronucleus assay at 20, 120, and 240 mg/kg. Pentostatin was not mutagenic to V79 Chinese hamster lung cells at the HGPRT locus exposed 3 hours to concentrations of 1 to 3 mg/mL, with or without metabolic activation. Pentostatin did not significantly increase chromosomal aberrations in V79 Chinese hamster lung cells exposed 3 hours to 1 to 3 mg/mL in the presence or absence of metabolic activation.
Impairment of Fertility: No fertility studies have been conducted in animals; however, in a 5-day intravenous toxicity study in dogs, mild seminiferous tubular degeneration was observed with doses of 1 and 4 mg/kg. The possible adverse effects on fertility in humans have not been determined. Advise patients on the potential risks for infertility.
Due to the genotoxicity and embryo-fetal toxicity findings in nonclinical studies, advise females of reproductive potential to use effective contraception during treatment and for 6 months following the last dose of NIPENT.
Due to the genotoxicity findings in nonclinical studies, advise male patients with female partners of reproductive potential to use effective contraception during treatment and for 3 months following the last dose of NIPENT.
It is not known whether NIPENT is excreted in human milk. Because many drugs are excreted in human milk, and because of the potential for serious adverse reactions in the breast-fed child due to pentostatin, advise patients not to breast-feed while on NIPENT therapy and for 1 week following the last dose of treatment.
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