Pentostatin

A to Z Drug Facts

Actions Pentostatin is a potent transition state inhibitor of the enzyme adenosine deaminase (ADA) that leads to cytotoxicity because of elevated intracellular levels of dATP which can block DNA synthesis through inhibition of ribonucleotide reductase. Pentostatin can also inhibit RNA synthesis as well as cause increased DNA damage. Following a single dose of 4 mg/m² infused over 5 min, the distribution half-life was 11 min, the mean terminal half-life was 5.7 hr, the mean plasma clearance was 68 mL/min/m², and approximately 90% of the dose was excreted in the urine as unchanged pentostatin or metabolites. Plasma protein binding of pentostatin is low, approximately 4%.

 Indications Hairy cell leukemia.

Palliative therapy of chronic lymphocytic leukemia, refractory acute lymphocytic leukemia, mycosis fungoides.

 Contraindications Standard considerations.

 Route/Dosage

Refractory Hairy Cell Leukemia

ADULTS: IV For patients with a Ccr at least 60 mL/min, give 4 mg/m² qod until complete response is achieved then give 2 additional doses. Assess patient response after 6 mo of therapy. If no response occurs, discontinue therapy. If a partial response occurs, continue therapy for no more than 6 more months then discontinue. Give 2 additional doses after achieving a complete response. Delay further therapy in patients whose absolute neutrophil count falls less than 200/mm³ from a baseline value greater than 500/mm³ and in patients with active infections, severe rash, or nervous system toxicity. Therapy may be resumed when these conditions resolve.

Interactions

Allopurinol

May enhance toxicity of pentostatin.

Fludarabine

Coadministration can result in severe pulmonary toxicity; coadministration is not recommended.

Vidarabine

Pentostatin may increase toxicity of vidarabine.

Lab Test Interferences None well documented.

 Adverse Reactions

CARDIOVASCULAR: Angina, CHF, acute arrhythmias, edema. CNS: Fatigue, headache, anxiety, insomnia, confusion, depression, paresthesia. DERMATOLOGIC: Erythematous, papular, vesiculobullous rashes, eczema, dry skin, urticaria. GI: Moderate potential for nausea and vomiting, anorexia, abdominal pain, diarrhea, mucositis, elevated LFTs. HEMATOLOGIC: Bone marrow suppression observed during first several courses of therapy, may represent disease-induced myelosuppression in hairy cell leukemia. HYPERSENSITIVITY: Anaphylactoid reaction. MUSCULOSKELETAL: Myalgia, arthralgia. RENAL: Increased serum creatinine, increased BUN, hematuria. RESPIRATORY: Cough, dyspnea. SPECIALSENSES: Abnormal vision, keratoconjunctivitis, ocular pain. OTHER: Fever, chills.

 Precautions

Pregnancy: Category D. Lactation: Undetermined. Children: Safety and efficacy have not been established. Adjustment in renal insufficiency: Dosage reduction may be required in patients with impaired renal failure (Ccr less than 60 mL/min). CNS toxicity: Withhold or discontinue therapy in those with evidence of CNS toxicity. Myelosuppression: Patients may experience myelosuppression, primarily during the first few courses of treatment. Rashes: Rashes, occasionally severe, were commonly reported and may worsen with continued treatment. Withholding of treatment may be required. Renal toxicity: In patients treated at the recommended dose, elevations in serum creatinine were usually minor and reversible. Some patients who began treatment with normal renal function had evidence of mild to moderate toxicity at a final assessment.

 Administration/Storage

• Refrigerate unopened vials. Reconstituted solutions of pentostatin 2 mg/mL are stable for no more than 72 hr at room temperature. After further dilution, pentostatin solutions are stable at room temperature for 24 hr. However, the manufacturer recommends disposal of pentostatin solutions within 8 hr of reconstitution.
• Reconstitute powder for injection with 5 mL sterile water for injection, shaking the vial to dissolve the powder; gives 2 mg/mL solution.
• For IV infusion, further dilute reconstituted solution with 25 or 50 mL of 5% Dextrose or 0.9% Sodium Chloride to a concentration of 0.18 to 0.33 mg/mL.
• Administer by IV bolus injection or IV infusion.

Pretreatment regimen

• Hydrate patients to reduce risk of renal toxicity.

IV bolus

• Give reconstituted solution by IV bolus injection over 5 min.

IV infusion

• Infuse diluted solution over 20 to 30 min.

 Assessment/Interventions

• Monitor CBC and renal function at baseline, prior to each course, and throughout the first few courses of therapy.
• Hyperuricemia may occur in patients with chronic lymphocytic leukemia because of rapid cell lysis; monitor serum uric acid. Minimize effects of hyperuricemia with hydration, urinary alkalinization, and allopurinol.

 Patient/Family Education

• Explain name, action, and potential side effects of drug.
• Advise patient, family, or caregiver that medication will be prepared and administered by health care provider in a health care setting.
• Review dosing schedule with patient, family, or caregiver.
• Advise patient, family, or caregiver to immediately report any of the following to health care provider: rash; itching; shortness of breath or difficulty breathing; fever, chills or other signs of infection; sores in mouth; unusual bleeding or bruising; pain, redness or swelling at injection site.
• Advise patient, family, or caregiver to report any of the following to health care provider: persistent stomach pain, diarrhea or appetite loss; persistent or worsening fatigue or general body weakness.
• Instruct patient to not take any prescription or otc medications or dietary supplements unless advised by health care provider.
• Caution women of childbearing potential to avoid becoming pregnant while being treated.
• Instruct women of childbearing potential to notify health care provider if they become pregnant, plan on becoming pregnant, or are breastfeeding.
• Advise patient that after discharge follow-up visits and laboratory tests will be required to monitor therapy and to be sure to keep appointments.

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Copyright © 2003 Facts and Comparisons
David S. Tatro
A to Z Drug Facts