Nipent

pentostatin

Nipent

Pharmacologic class: Antimetabolite

Therapeutic class: Antineoplastic

Pregnancy risk category D

FDA Box Warning

• Give under supervision of physician experienced in cancer chemotherapy, in facility with adequate diagnostic and treatment resources.

• Use of higher dosages than those specified isn't recommended, as dose-limiting severe renal, liver, pulmonary, and CNS toxicities may occur.

• In study of patients with refractory chronic lymphocytic leukemia receiving drug at recommended dosage in combination with fludarabine, four of six patients had severe or fatal pulmonary toxicity. Use in combination with fludarabine isn't recommended.

Action

Unknown. Thought to inhibit adenosine deaminase, thereby increasing levels of deoxyadenosine triphosphate in cells, blocking DNA synthesis, and inhibiting ribonucleotide reductase.

Availability

Powder for injection: 10-mg vials

Indications and dosages

➣ Hairy cell leukemia

Adults: 4 mg/m2 I.V. every other week

Contraindications

• Hypersensitivity to drug

Precautions

Use cautiously in:

• renal disease, bone marrow depression

• pregnant or breastfeeding patients

• children.

Administration

• Before giving, hydrate patient with 500 to 1,000 ml of dextrose 5% and normal saline solution (or its equivalent). After administering, give 500 ml of dextrose 5% in water (D5W) or its equivalent.

See Follow facility protocol for handling, administering, and disposing of chemotherapeutic drugs.

• Give by direct I.V. bolus injection or dilute with 25 to 50 ml of D5W or normal saline solution; infuse over 20 to 30 minutes.

Adverse reactions

CNS: headache, malaise, anxiety, confusion, depression, dizziness, insomnia, nervousness, paresthesia, drowsiness, abnormal thinking, fatigue, asthenia, hallucinations, hostility, amnesia

CV: peripheral edema, cellulitis, vasculitis, hypotension, angina, tachycardia, bradycardia, phlebitis, thrombophlebitis, cardiac arrest, heart failure, hemorrhage, ventricular asystole, pericardial effusion, sinus arrest

EENT: abnormal vision, nonreactive pupils, photophobia, retinopathy, eye pain, conjunctivitis, dry or watery eyes, hearing loss, tinnitus, ear pain, epistaxis, pharyngitis, rhinitis

GI: nausea, vomiting, diarrhea, constipation, dyspepsia, abdominal pain, ileus, flatulence, stomatitis, glossitis, anorexia

GU: amenorrhea, breast lump, erectile dysfunction, decreased libido, renal calculi, renal dysfunction, renal insufficiency, renal failure

Hematologic: ecchymosis, anemia, hemolytic anemia, agranulocytosis, aplastic anemia, leukopenia, thrombocytopenia

Metabolic: hyperuricemia, hypercalcemia, hyponatremia

Musculoskeletal: myalgia, joint pain

Respiratory: cough, dyspnea, respiratory tract infection, pulmonary embolism

Skin: rash, eczema, petechiae, dry skin, pruritus, skin disorder, furunculosis, acne, alopecia, diaphoresis, photosensitivity

Other: unusual taste, gingivitis, fever, chills, pain, facial edema, lymphadenopathy, herpes simplex or herpes zoster infection, flulike symptoms, viral or bacterial infection, allergic reaction, sepsis, neoplasm

Interactions

Drug-drug. Allopurinol: hypersensitiv-ity vasculitis

Carmustine, cyclophosphamide, etoposide: potentially fatal acute pulmonary edema and hypotension

Fludarabine: severe or fatal pulmonary toxicity.

Vidarabine: increased risk and severity of adverse reactions

Drug-diagnostic tests. Calcium, liver

function tests, serum uric acid: increased values

Granulocytes, platelets, sodium, white blood cells: decreased levels

Patient monitoring

See Monitor CBC (including platelet count). Watch for evidence of blood dyscrasias.

• Assess kidney and liver function tests. Stay alert for evidence of organ dysfunction.

• Monitor temperature. Watch for signs and symptoms of bacterial and viral infection.

• Closely monitor vital signs and ECG, particularly for life-threatening arrhythmias, heart failure, and pulmonary edema.

Patient teaching

See Tell patient drug lowers resistance to infection. Instruct him to avoid crowds and to immediately report fever, cough, sore throat, and other infection symptoms.

• Advise patient to minimize GI upset by eating small, frequent servings of food and drinking plenty of fluids.

• Instruct female patient of childbearing age to avoid pregnancy during drug therapy and to seek medical advice before becoming pregnant.

• Caution patient to avoid driving and other hazardous activities until he knows how drug affects concentration and alertness.

• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs and tests mentioned above.

pentostatin

(pen-toe-sta-tin) pentostatin,

Nipent

(trade name)

Classification

Therapeutic: antineoplastics
Pharmacologic: enzyme inhibitors
Pregnancy Category: D

Indications

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

Action

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).

Pharmacokinetics

Absorption: IV administration results in complete bioavailability.Distribution: Highest in the kidneys; minimal penetration into the CNS.Metabolism and Excretion: 90% renally excreted.Half-life: 6 hr (increased in renal impairment).

Time/action profile (clinical response)

ROUTEONSETPEAKDURATION
IV4.7 mounknown>7.7 mo (range 1.4–35.1 mo)†
†Inhibition of adenine deaminase lasts for >1 wk after administration

Contraindications/Precautions

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; Obstetric / Lactation / Pediatric: Pregnancy, lactation, or children (safety not established).

Adverse Reactions/Side Effects

Central nervous system

  • CNS toxicity (most frequent)
  • fatigue (most frequent)
  • headache (most frequent)
  • weakness (most frequent)

Ear, Eye, Nose, Throat

  • epistaxis
  • keratoconjunctivitis
  • pharyngitis
  • rhinitis
  • sinusitis
  • vision changes

Respiratory

  • pulmonary toxicity (life-threatening)
  • bronchitis
  • dyspnea
  • pneumonia
  • cough (most frequent)
  • pulmonary edema

Cardiovascular

  • MI (life-threatening)
  • angina pectoris
  • arrhythmias
  • thrombophlebitis

Gastrointestinal

  • anorexia (most frequent)
  • diarrhea (most frequent)
  • hepatotoxicity (most frequent)
  • nausea (most frequent)
  • vomiting (most frequent)
  • constipation
  • flatulence
  • abdominal pain (most frequent)
  • stomatitis (most frequent)

Genitourinary

  • renal toxicity

Dermatologic

  • itching (most frequent)
  • skin rash (most frequent)
  • dry skin

Hematologic

  • anemia
  • leukopenia (most frequent)
  • thrombocytopenia (most frequent)

Musculoskeletal

  • arthralgia
  • myalgia (most frequent)

Miscellaneous

  • allergic reactions including anaphylaxis (life-threatening)
  • fever (most frequent)
  • flu-like syndrome
  • weight loss

Interactions

Drug-Drug interaction

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

Route/Dosage

Intravenous (Adults) 4 mg/m2 every other week.

Availability

Powder for injection: 10 mg/vial

Nursing implications

Nursing assessment

  • 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.

Potential Nursing Diagnoses

Risk for infection (Side Effects)
Deficient knowledge, related to medication regimen (Patient/Family Teaching)

Implementation

  • high alert: 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.
    • Administration of live vaccines to immunocompromised patients should be avoided.
    • Solution should be prepared in a biologic cabinet. Wear gloves, gown, and mask while handling medication. Discard equipment in specially designated containers (see ). Spills and wastes should be treated with 5% sodium hypochlorite solution before disposal.
    • for a.
  • Intravenous 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.
  • Y-Site Compatibility: fludarabine, melphalan, ondansetron, paclitaxel, sargramostim
  • Solution Compatibility: 0.9% NaCl, lactated Ringer’s injection

Patient/Family Teaching

  • 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.

Evaluation/Desired Outcomes

  • 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®

Pentostatin, see there.

Nipent

A brand name for PENTOSTATIN.