pentostatin

PEN-toe-sta-tin

Therapeutic Classification: antineoplastics

Pharmacologic Classification: enzyme inhibitors

High Alert

Treatment of hairy-cell leukemia in patients with active disease.

Inhibits adenine deaminase (ADA), an enzyme that blocks the synthesis of DNA, especially in T cells of the lymphoid system.

Therapeutic effects:

Decreased signs and symptoms of hairy-cell leukemia (recovery of hematologic parameters, organomegaly, and lymphadenopathy).

Absorption: IV administration results in complete bioavailability.

Distribution: Highest in the kidneys; minimal penetration into the CNS.

Metabolism/Excretion: 90% renally excreted.

Half-Life: 6 hr (↑ in renal impairment).

(clinical response)

ROUTE	ONSET	PEAK	DURATION
IV	4.7 mo	unknown	>7.7 mo (range 1.4–35.1 mo)‡

‡Inhibition of adenine deaminase lasts for >1 wk after administration.

Contraindicated in:

Hypersensitivity to pentostatin or mannitol;
Concurrent use of fludarabine (↑ risk of potentially fatal pulmonary toxicity).

Use Cautiously in:

Cardiovascular disease, seizures, or pre-existing renal, hepatic, or pulmonary disease or other chronic debilitating illness;
Patients with childbearing potential;
OB: Safety not established.

CV: MI, angina pectoris, arrhythmias, thrombophlebitis

Derm: itching, skin rash, dry skin

EENT: epistaxis, keratoconjunctivitis, pharyngitis, rhinitis, sinusitis, vision changes

GI: abdominal pain, anorexia, diarrhea, hepatotoxicity, nausea, stomatitis, vomiting, constipation, flatulence

GU: renal toxicity

Hemat: leukopenia, thrombocytopenia, anemia

MS: myalgia, arthralgia

Neuro: CNS toxicity, fatigue, headache, weakness

Resp: cough, pneumonia, bronchitis, dyspnea, pulmonary edema, PULMONARY TOXICITY

Misc: fever, ANAPHYLAXIS ALLERGIC REACTIONS INCLUDING , flu-like syndrome, weight loss

Drug-drug:

Risk of fatal pulmonary toxicity ↑ by concurrent use of fludarabine.
Effects of vidarabine↑ by pentostatin, which may result in increased toxicity of both agents.

IV (Adults ): 4 mg/m² every other week.

(Generic available)

Powder for injection: 10 mg/vial

Monitor patient for CNS toxicity, which initially manifests as lethargy and may progress to anxiety, nervousness, confusion, mental depression, numbness or tingling in hands or feet, sleepiness, and trouble sleeping. With high doses, CNS toxicity may lead to seizures, coma, and death. Dose should be withheld in patients manifesting CNS toxicity.
Monitor intake and output and renal function; provide adequate hydration. Administer 500–1000 mL of D5/0.45% NaCl before administration and 500 mL of D5W or a similar solution after administration of pentostatin. Antiemetics should be administered for 48–72 hr after therapy.
Monitor patient for allergic reactions, including anaphylactic reactions, rash, and itching. Therapy should be discontinued if severe rash or anaphylaxis develops. Epinephrine, an antihistamine, and resuscitation equipment should be available during therapy.
Monitor for bone marrow depression. Assess for bleeding (bleeding gums, bruising, petechiae, guaiac stools, urine, and emesis) and avoid IM injections and rectal temperatures if platelet count is low. Apply pressure to venipuncture sites for 10 min. Assess for signs of infection during neutropenia. Anemia may occur. Monitor for increased fatigue, dyspnea, and orthostatic hypotension.

Lab Test Considerations:

Before initiating therapy, assess renal function by measuring serum creatinine or CCr. Measure serum creatinine before each dose. Dose may be withheld if serum creatinine is ↑.
- Monitor CBC with differential and platelet count before each dose and periodically during therapy. Temporarily withhold pentostatin if absolute neutrophil count (ANC) is <200 cells/mm³ during treatment in a patient whose initial neutrophil count was >500 cells/mm³. Resume treatment when ANC returns to pretreatment levels.
- May cause transiently ↑ serum alkaline phosphatase, AST, ALT, and LDH in most patients.
- Monitor peripheral blood for hairy cells periodically throughout therapy to determine response to treatment.
- Monitor serum uric acid concentrations before and periodically throughout therapy. May cause ↑ serum uric acid concentrations.
- Bone marrow aspiration and biopsies may be required every 2–3 mo to assess response to therapy.

Fatalities have occurred with incorrect administration of chemotherapeutic agents. Before administering, clarify all ambiguous orders; double check single, daily, and course-of-therapy dose limits; have second practitioner independently double check original order, calculations and infusion pump settings. Clarify orders that do not include generic and brand names.
Pentostatin should be administered under the supervision of a physician experienced in the use of antineoplastic agents.
- Avoid administration of live vaccines to immunocompromised patients.
- Prepare solution in a biologic cabinet. Wear gloves, gown, and mask while handling medication. Discard equipment in specially designated containers. Spills and wastes should be treated with 5% sodium hypochlorite solution before disposal.

IV Administration:

Diluent: Reconstitute by adding 5 mL of sterile water for injection to each 10-mg vial. Shake thoroughly to ensure complete dissolution of the drug. May be administered without further undiluted.Concentration: Concentration will be 2 mg/mL. .
Rate: Administer as a bolus injection over 5 min.
Intermittent Infusion: Diluent: Dilute in 25–50 mL of D5W or 0.9% NaCl for concentrations of 0.33 or 0.18 mg/mL, respectively. Solutions are stable for 8 hr at room temperature. Discard unused solution.
Rate: Administer over 20–30 min.

Instruct patient to notify health care professional immediately if rash or signs of anaphylaxis develop.
Instruct patient to notify health care professional promptly if fever; chills; cough; hoarseness; sore throat; signs of infection; lower back or side pain; painful or difficult urination; bleeding gums; bruising; petechiae; blood in stools, urine, or emesis; increased fatigue; dyspnea; or orthostatic hypotension occurs. Caution patient to avoid crowds and persons with known infections. Instruct patient to use soft toothbrush and electric razor and to avoid falls. Caution patient not to drink alcoholic beverages or take medication containing aspirin or NSAIDs; may precipitate gastric bleeding.
Advise patient to use sunscreen and protective clothing to prevent photosensitivity reactions.
Instruct patient not to receive any vaccinations without advice of health care professional.
Emphasize need for periodic lab tests to monitor for side effects.

Decrease in number of hairy cells in the peripheral blood and bone marrow.
Decreased organomegaly.
Decreased lymphadenopathy. Pentostatin is usually continued for 2 doses after a complete response is achieved. If a partial response is achieved, pentostatin is continued for 12 mo. If neither a complete nor partial response is achieved in 6 mo, pentostatin therapy is discontinued.

Nipent

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US Brand Names ⬆