Pentostatin

Pentostatin is used to treat hairy cell leukemia (cancer of a certain type of white blood cell).

This medication may be prescribed for other uses. Ask your doctor or pharmacist for more information.

Tell your doctor if you are breastfeeding or plan to breastfeed.

It is not known if this medication crosses into human milk. Because many medications can cross into human milk and because of the possibility for serious adverse reactions in nursing infants with use of this medication, a choice should be made whether to stop nursing or stop the use of this medication. Your doctor and you will decide if the benefits outweigh the risk of using this medication.

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 pentostatin 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.

Pentostatin should be administered under the supervision of a physician qualified and experienced in the use of cancer chemotherapeutic agents. The use of higher doses than those specified is not recommended. Dose-limiting severe renal, liver, pulmonary, and CNS toxicities occurred in Phase 1 studies that used pentostatin at higher doses (20-50 mg/m2 in divided doses over 5 days) than recommended.

In a clinical investigation in patients with refractory chronic lymphocytic leukemia using pentostatin at the recommended dose in combination with fludarabine phosphate, 4 of 6 patients entered in the study had severe or fatal pulmonary toxicity. The use of pentostatin in combination with fludarabine phosphate is not recommended.

Pentostatin is a cancer medication that interferes with the growth and spread of cancer cells in the body.

Pentostatin is used to treat hairy cell leukemia (a type of blood cancer).

Pentostatin may also be used for purposes not listed in this medication guide.

Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have:

• fever, swollen glands, cold or flu symptoms, blisters or ulcers in your mouth, red or swollen gums, trouble swallowing;

• pale skin, weakness, easy bruising, unusual bleeding (nose, mouth, vagina, or rectum), purple or red pinpoint spots under your skin;

• swelling, rapid weight gain, little or no urinating, pain in your side or lower back;

• red or pink urine;

• skin sores, severe skin rash;

• anxiety, sweating, severe shortness of breath, wheezing, gasping for breath, chest pain, fast or uneven heart rate;

• cough with foamy mucus, cough with yellow or green mucus;

• eye pain, vision problems; or

• numbness, tingling, or burning pain.

Common side effects may include:

• loss of appetite, nausea, vomiting;

• constipation, diarrhea;

• joint or muscle pain;

• headache, dizziness, drowsiness, depressed mood; or

• sleep problems (insomnia).

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Usual Adult Dose for Hairy Cell Leukemia:

For use as single agent treatment for both untreated and alpha interferon refractory hairy cell leukemia patients with active disease (as defined by clinically significant anemia, neutropenia, thrombocytopenia, or disease related symptoms):
4 mg/m2 every other week. (Higher doses are not recommended.)

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.

It is recommended that patients receive hydration with 500 to 1,000 mL of 5% Dextrose in 0.5 Normal Saline or equivalent before Pentostatin administration. An additional 500 mL of 5% Dextrose or equivalent should be administered after Pentostatin is given.

The recommended dosage of Pentostatin for the treatment of hairy cell leukemia is 4 mg/m2 every other week. Pentostatin may be administered intravenously by bolus injection or diluted in a larger volume and given over 20 to 30 minutes. (See Preparation of Intravenous Solution.)

Higher doses are not recommended.

No extravasation injuries were reported in clinical studies.

The optimal duration of treatment has not been determined. In the absence of major toxicity and with observed continuing improvement, the patient should be treated until a complete response has been achieved. Although not established as required, the administration of two additional doses has been recommended following the achievement of a complete response.

All patients receiving Pentostatin at 6 months should be assessed for response to treatment. If the patient has not achieved a complete or partial response, treatment with Pentostatin should be discontinued.

If the patient has achieved a partial response, Pentostatin treatment should be continued in an effort to achieve a complete response. At any time thereafter that a complete response is achieved, two additional doses of Pentostatin are recommended. Pentostatin treatment should then be stopped. If the best response to treatment at the end of 12 months is a partial response, it is recommended that treatment with Pentostatin be stopped.

Withholding or discontinuation of individual doses may be needed when severe adverse reactions occur. Drug treatment should be withheld in patients with severe rash, and withheld or discontinued in patients showing evidence of nervous system toxicity.

Pentostatin treatment should be withheld in patients with active infection occurring during the treatment but may be resumed when the infection is controlled.

Patients who have elevated serum creatinine should have their dose withheld and a creatinine clearance determined. There are insufficient data to recommend a starting or a subsequent dose for patients with impaired renal function (creatinine clearance <60 mL/min).

Patients with impaired renal function should be treated only when the potential benefit justifies the potential risk. Two patients with impaired renal function (creatinine clearances 50 to 60 mL/min) achieved complete response without unusual adverse events when treated with 2 mg/m2.

No dosage reduction is recommended at the start of therapy with Pentostatin in patients with anemia, neutropenia, or thrombocytopenia. In addition, dosage reductions are not recommended during treatment in patients with anemia and thrombocytopenia if patients can be otherwise supported hematologically. Pentostatin should be temporarily withheld if the absolute neutrophil count falls during treatment below 200 cells/mm3 in a patient who had an initial neutrophil count greater than 500 cells/mm3 and may be resumed when the count returns to predose levels.

Preparation of Intravenous Solution

1. Procedures for proper handling and disposal of anticancer drugs should be followed. Several guidelines on this subject have been published.2-7 There is no general agreement that all of the procedures recommended in the guidelines are necessary or appropriate. Spills and wastes should be treated with a 5% sodium hypochlorite solution prior to disposal.

2. Protective clothing including polyethylene gloves must be worn.

3. Transfer 5 mL of sterile water for injection to the vial containing Pentostatin and mix thoroughly to obtain complete dissolution of a solution yielding 2 mg/mL. Parenteral drug products should be inspected visually for particulate matter and discoloration prior to administration.

4. Pentostatin may be given intravenously by bolus injection or diluted in a larger volume (25 to 50 mL) with 5% dextrose injection or 0.9% sodium chloride injection. Dilution of the entire contents of a reconstituted vial with 25 mL or 50 mL provides a Pentostatin concentration of 0.33 mg/mL or 0.18 mg/mL, respectively, for the diluted solutions.

5. Pentostatin solution when diluted for infusion with 5% dextrose injection or 0.9% sodium chloride injection does not interact with PVC infusion containers or administration sets at concentrations of 0.18 mg/mL to 0.33 mg/mL.

Stability

Pentostatin vials are stable at refrigerated storage temperature 2° to 8°C (36° to 46°F) for the period stated on the package. Vials reconstituted or reconstituted and further diluted as directed may be stored at room temperature and ambient light but should be used within 8 hours because Pentostatin contains no preservatives.

(pen toe STAT in)

• 2′-Deoxycoformycin
• Co-Vidarabine
• dCF
• Deoxycoformycin

Excipient information presented when available (limited, particularly for generics); consult specific product labeling.

Solution Reconstituted, Intravenous:

Nipent: 10 mg (1 ea)

• Antineoplastic Agent, Antimetabolite
• Antineoplastic Agent, Antimetabolite (Purine Analog)

Acute graft-versus-host disease (treatment)

Data from a phase II study (initial therapy for acute graft-versus-host disease [GVHD]) and a phase I study in steroid-refractory acute GVHD support the use of pentostatin in the management of acute GVHD [Alousi 2009], [Bolanos-Meade 2005]. Additional trials may be necessary to further define the role of pentostatin in the treatment of this condition.

Chronic graft-versus-host disease, steroid-refractory (treatment)

Data from two phase II studies in steroid-refractory chronic GVHD also support the use of pentostatin in the management of chronic GVHD [Jacobsohn 2007], [Jacobsohn 2009]. Additional trials may be necessary to further define the role of pentostatin in the treatment of this condition.

Based on the American Society for Blood and Marrow Transplant (ASBMT) Consensus Conference on Clinical Practice in Chronic GVHD: Second-Line Treatment of Chronic Graft-versus-Host Disease, pentostatin may be given for the management of steroid-refractory chronic graft-versus-host disease (GVHD), although the best results have been in children with chronic GVHD.

Chronic lymphocytic leukemia

Data from two studies (one in previously-treated and one in previously-untreated patients) supports the use of pentostatin (in combination with cyclophosphamide and rituximab) for the treatment of chronic lymphocytic leukemia [Kay 2007], [Lamanna 2006]. Additional trials may be necessary to further define the role of pentostatin in the treatment of this condition.

Cutaneous T-cell lymphomas, mycosis fungoides/Sezary syndrome

Data from a phase II study in patients with T-cell malignancies supports the use of pentostatin in the treatment of the cutaneous T-cell lymphomas mycosis fungoides and Sezary syndrome [Ho 1999]. Additional trials may be necessary to further define the role of pentostatin in the treatment of this condition.

T-cell prolymphocytic leukemia, refractory

Data from a small phase II study in patients with T-cell malignancies supports the use of pentostatin (in combination with alemtuzumab) in the treatment of refractory T-cell prolymphocytic leukemia [Ravandi 2009]. In addition, data from a retrospective study of patients with T-cell malignancies supports the use of pentostatin in the treatment of the T-cell prolymphocytic leukemia [Mercieca 1994]. Additional trials may be necessary to further define the role of pentostatin in the treatment of this condition.

Chronic graft-versus-host disease (GVHD), steroid-refractory: IV: 4 mg/m2 once every 2 weeks; discontinue after 6 months for sustained objective response, or continue every 2 to 4 weeks for up to 12 months if still improving (Jacobsohn, 2007; Jacobsohn, 2009) or 4 mg/m2 once every 2 weeks for 3 months (Wolff, 2011)

There are no dosage adjustments provided in the manufacturer’s labeling.

American Society of Clinical Oncology (ASCO) Guidelines for appropriate chemotherapy dosing in obese adults with cancer: Utilize patient’s actual body weight (full weight) for calculation of body surface area- or weight-based dosing, particularly when the intent of therapy is curative; manage regimen-related toxicities in the same manner as for nonobese patients; if a dose reduction is utilized due to toxicity, consider resumption of full weight-based dosing with subsequent cycles, especially if cause of toxicity (eg, hepatic or renal impairment) is resolved (Griggs, 2012).

American Society for Blood and Marrow Transplantation (ASBMT) practice guideline committee position statement on chemotherapy dosing in obesity: Utilize actual body weight (full weight) for calculation of body surface area in pentostatin dosing for hematopoietic stem cell transplant conditioning regimens in adults (Bubalo, 2014).

Reconstitute with 5 mL SWFI to a concentration of 2 mg/mL. The solution may be further diluted in 25 to 50 mL NS or D5W for infusion. When diluted for infusion in D5W or NS at concentrations of 0.18 to 0.33 mg/mL, pentostatin is compatible with PVC containing infusion bags and infusion sets.

Administer IV over 20 to 30 minutes or as a bolus infusion. Hydrate with 500 to 1,000 mL fluid prior to infusion and 500 mL after infusion.

Store intact vials under refrigeration at 2°C to 8°C (36°F to 46°F). Reconstituted vials and solutions diluted for infusion (in D5W or NS) may be stored at room temperature for 8 hours.

Concerns related to adverse effects:

• Bone marrow suppression: Myelosuppression may occur, primarily early in treatment (first few courses). Neutropenia may worsen during initial courses for the treatment of hairy cell leukemia. If severe neutropenia persists beyond early cycles, evaluate for disease status. Monitor blood counts during treatment (more frequently in the initial cycles).

• CNS toxicity: [U.S. Boxed Warnings]: Severe CNS toxicities have occurred with doses higher than recommended; do not exceed the recommended dose. Withhold treatment or discontinue for CNS toxicity.

• Hepatotoxicity: [U.S. Boxed Warnings]: Severe liver toxicities have occurred with doses higher than recommended; do not exceed the recommended dose. May cause elevations (usually reversible) in liver function tests.

• Pulmonary toxicity: [U.S. Boxed Warnings]: Severe pulmonary toxicities have occurred with doses higher than recommended; do not exceed the recommended dose. Do not administer concurrently with fludarabine; concomitant use has resulted in serious or fatal pulmonary toxicity.

• Rash: Severe rashes may occur and worsen with therapy continuation; may require treatment interruption or discontinuation.

• Renal toxicity: [U.S. Boxed Warnings]: Severe renal toxicities have occurred with doses higher than recommended; do not exceed the recommended dose. Serum creatinine elevations occurring at recommended doses are usually minor and reversible. Withhold treatment for elevated serum creatinine and determine creatinine clearance. May require dosage adjustment or therapy discontinuation.

Disease-related concerns:

• Infections: In patients who present with infections prior to treatment, infections should be resolved, if possible, prior to initiation of treatment; preexisting infections may worsen with pentostatin treatment. Treatment should be temporarily withheld for active infections during therapy. Use in patients with infections only if the potential benefit justifies the potential risk.

• Renal impairment: Use with caution in patients with renal dysfunction (CrCl <60 mL/minute); the terminal half-life is prolonged; may require dosage adjustment.

Concurrent drug therapy issues:

• Drug-drug interactions: Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information. Concurrent use with fludarabine has resulted in severe or fatal pulmonary toxicity and is not recommended. Fatal pulmonary edema and hypotension have been reported in patients treated with pentostatin in combination with carmustine, etoposide, or high-dose cyclophosphamide as part of a myeloablative regimen for bone marrow transplant.

Other warnings/precautions:

• Experienced physician: [U.S. Boxed Warning]: Should be administered under the supervision of an experienced cancer chemotherapy physician.

For use as single agent treatment for both untreated and alpha interferon refractory hairy cell leukemia patients with active disease (as defined by clinically significant anemia, neutropenia, thrombocytopenia, or disease related symptoms):
4 mg/m2 every other week. (Higher doses are not recommended.)

There are insufficient data to recommend a starting or a subsequent dose for patients with impaired renal function (creatinine clearance <60 mL/min)