Nipent

Your doctor will perform blood tests to make sure you do not have conditions that would prevent you from safely receiving pentostatin.

Pentostatin is injected into a vein through an IV. A healthcare provider will give you this injection.

You may need frequent medical tests at your doctor's office to be sure this medication is not causing harmful effects. Your cancer treatments may be delayed based on the results of these tests. You may also need to have a bone marrow biopsy.

Seek emergency medical attention or call the Poison Help line at 1-800-222-1222.

Call your doctor for instructions if you miss an appointment for your pentostatin injection.

Medications can interact with certain foods. In some cases, this may be harmful and your doctor may advise you to avoid certain foods. In the case of this medication, there are no specific foods that you must exclude from your diet.

Nipent comes as a powder to be mixed with liquid and injected into a vein by a healthcare professional. It is usually injected once every other week.

Take this medication exactly as prescribed by your doctor. Follow the directions on your prescription label carefully.
The dose your doctor recommends may be based on the following:

• the condition being treated
• other medical conditions you have
• other medications you are taking
• how you respond to this medication
• your weight
• your height
• your age
• your gender

The recommended dosage of Nipent is 4 mg/m² every other week.

Because this medication is administered by a healthcare provider in a medical setting, it is unlikely that an overdose will occur. However, if overdose is suspected, seek emergency medical attention.

Hairy Cell Leukemia

Used alone as first-line therapy for active hairy cell leukemia (leukemic reticuloendotheliosis), defined as disease involving clinically relevant anemia, neutropenia, thrombocytopenia, or disease-related symptoms.1 15 59

Used in patients with active hairy cell leukemia that responds inadequately to, or progresses during, interferon alfa therapy (i.e., disease that progresses despite ≥3 months of interferon alfa therapy or fails to respond to ≥6 months of therapy).1 15 59 97 110

Pentostatin or cladribine considered first-line therapy because of apparent greater efficacy (i.e., higher complete response rate) compared with interferon alfa;15 59 99 100 101 102 103 104 105 106 107 however, cladribine may be preferred.99 100 103 105 106 107

Chronic Lymphocytic Leukemia (CLL)

Used alone or in combination with other agents for treatment of chronic lymphocytic leukemia (CLL)†.22 59

Cutaneous T-cell Lymphoma

Treatment of cutaneous T-cell lymphoma†59 (e.g., mycosis fungoides†, Sézary syndrome†).2 76 77 85 119

General

• Consult specialized references for procedures for proper handling and disposal of antineoplastics.1

• Hydrate with 500–1000 mL of 5% dextrose in 0.45% sodium chloride injection or a similar IV fluid prior to pentostatin administration; hydrate with an additional 500 mL of 5% dextrose or a similar IV fluid immediately after pentostatin administration to minimize risk of adverse renal effects.1 3 11 97 (See Renal Effects under Cautions.)

Administration

For solution and drug compatibility information, see Compatibility under Stability.

Administer by IV infusion or direct IV injection.1

Handle cautiously; use of protective clothing and polyethylene gloves recommended during preparation of IV solution.1 Treat spills and waste with 5% sodium hypochlorite solution prior to disposal.1 97

Reconstituted and diluted solutions contain no preservatives; use within 8 hours of preparation.1

IV Administration

Reconstitute vial containing 10 mg of lyophilized pentostatin by adding 5 mL of sterile water for injection to provide a solution containing 2 mg/mL.1 Shake thoroughly to ensure complete dissolution of the drug.1 97

Prior to administration by IV infusion, must be diluted in 5% dextrose injection or 0.9% sodium chloride injection.1 Dilute entire contents of reconstituted vial with 25 or 50 mL of 5% dextrose injection or 0.9% sodium chloride injection to provide solutions containing 0.33 or 0.18 mg/mL, respectively.1

Administer by IV infusion over 20–30 minutes.1 97

Administer by IV injection over 5 minutes.1 9 97

Dosage

Adults

4 mg/m2 as a single dose every other week.1 3 4 Higher dosages not recommended.1 (See Prescribing Limits under Dosage and Administration.)

Optimum duration of therapy not determined.1 If clinical improvement is observed (in the absence of any major toxicity), continue therapy until a complete response is achieved.1 Clinical evidence suggests 2 additional doses following achievement of a complete response.1 97 98

If a complete or partial response is not achieved after 6 months of therapy, discontinue therapy.1 If a partial response is achieved, continue therapy until a complete response is achieved.1 If after 12 months of therapy only a partial response is achieved, discontinue therapy.1

Patients with initial ANC >500 cells/mm3: If ANC decreases during treatment to <200 cells/mm3, temporarily withhold therapy and resume when ANC returns to predose levels.1

No dosage adjustments necessary when starting therapy in patients with anemia, neutropenia, or thrombocytopenia.1

Dosage adjustments not necessary during treatment in patients with thrombocytopenia or anemia managed with appropriate hematologic monitoring and/or therapy.1

If patient exhibits evidence of nervous system toxicity (e.g., lethargy, seizures, coma), withhold or discontinue therapy.1

If patient experiences a severe rash, withhold therapy.1

In patients with an active underlying infection, withhold therapy.1 Resume therapy once infection is controlled.1

Withhold individual doses and determine Clcr in patients with an increased predose Scr.1 (See Renal Impairment under Dosage and Administration.)

Prescribing Limits

Adults

Maximum 4 mg/m2 as a single dose every other week.1 3 4 Risk of severe toxicity (e.g., renal, hepatic, pulmonary, CNS) increases with higher dosages (e.g., 20–50 mg/m2 in divided doses over 5 days).1 2 97 98

Not recommended more frequently than every 2 weeks;2 97 98 if weekly therapy is used, ≤3 successive weekly doses recommended by some clinicians.2

Patients unable to achieve a complete or partial response to therapy: Maximum 6 months.1

Patients with only a partial response to therapy: Maximum 12 months.1

Special Populations

Hepatic Impairment

No specific dosage recommendations at this time.1

Renal Impairment

Withhold individual doses and determine Clcr in patients with an elevated predose Scr.1

Insufficient data to recommend an initial or subsequent dose of pentostatin in patients with impaired renal function (i.e., Clcr<60 mL/minute); 2 patients with Clcr of 50–60 mL/minute achieved complete responses without unusual toxicity when treated with 2 mg/m2 of pentostatin.1

Administer to patients with impaired renal function only when potential benefits justify possible risks of toxicity.1 2 98 (See Renal Effects under Cautions.)

Geriatric Patients

Select dosage with caution, usually starting at the low end of the dosing range, because of age-related decreases in hepatic, renal, and/or cardiac function and concomitant disease and drug therapy.1

Pentostatin belongs to the group of medicines called antimetabolites. It is used to treat a type of cancer of the white blood cells called hairy cell leukemia. This medicine may be used in patients with hairy cell leukemia who have already been treated with other medicines (e.g., alpha-interferon) that did not work well.

Pentostatin interferes with the growth of cancer cells, which are eventually destroyed. Since the growth of normal body cells may also be affected by pentostatin, other effects may also occur. Some of these may be serious and must be reported to your doctor. Other effects may not be serious but may cause concern. Some effects may not occur for months or years after the medicine is used.

Before you begin treatment with pentostatin, you and your doctor should talk about the good this medicine will do as well as the risks of using it.

This medicine is to be administered only by or under the immediate supervision of your doctor.

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

• Upset stomach or throwing up.
• Feeling tired or weak.
• Headache.
• Loose stools (diarrhea).
• Belly pain.
• Not hungry.
• Runny nose.
• Itching.
• Mouth irritation or mouth sores.
• Sweating a lot.
• Muscle or joint pain.
• Signs of a common cold.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.

• If you need to store this medicine at home, talk with your doctor, nurse, or pharmacist about how to store it.

General

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.

Information for Patients

Patients should be advised of the signs and symptoms of adverse events associated with Nipent therapy. (See ADVERSE REACTIONS.)

Laboratory Tests

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 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.

Drug Interactions

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, Mutagenesis, Impairment of Fertility

No animal carcinogenicity studies have been conducted with pentostatin.

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.

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.

Pregnancy

(See WARNINGS)

Nursing Mothers

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 nursing infants from pentostatin, a decision should be made whether to discontinue nursing or discontinue the drug, taking into account the importance of Nipent to the mother.

Pediatric Use

Safety and effectiveness in children or adolescents have not been established.

Nipent (pentostatin for injection) is supplied as a sterile lyophilized white to off-white powder in single-dose vials containing 10 mg of pentostatin. The vials are packed in individual cartons.

NDC 0409-0801-09.

Storage

Store Nipent vials under refrigerated storage conditions 2° to 8° C (36° to 46°F).