etoposide phosphate


etoposide (VP-16-213)

Eposin (UK), Toposar, VePesid

etoposide phosphate

Etopophos

Pharmacologic class: Podophyllotoxin derivative

Therapeutic class: Antineoplastic

Pregnancy risk category D

Action

Damages DNA before mitosis by inhibiting topoisomerase II enzyme. This action impairs DNA synthesis and inhibits selected cancer cell growth. Cell-cycle-phase specific.

Availability

Capsules: 50 mg

Injection: 20 mg/ml

Powder for injection (phosphate): 100 mg in single-dose vials

Indications and dosages

➣ Testicular cancer

Adults: 50 to 100 mg/m2 I.V. daily for 5 days. Or 100 mg/m2 I.V. on days 1,3, and 5, with course repeated q 3 to 4 weeks.

➣ Small-cell carcinoma of lung

Adults: 70 mg/m2 (rounded up or down to nearest 50 mg) P.O. daily for 4 days, then a maximum of 100 mg/m2 (rounded up or down to nearest 50 mg) P.O. daily for 5 days every 3 to 4 weeks. Alternatively, 35 mg/m2 I.V. daily for 4 days, then a maximum of 50 mg/m2 I.V. daily for 5 days q 3 to 4 weeks.

Dosage adjustment

• Renal impairment

Off-label uses

• AIDS-related Kaposi's sarcoma

• Wilms' tumor

• Neuroblastoma

• Malignant lymphoma

• Hodgkin's disease

• Ovarian neoplasms

Contraindications

• Hypersensitivity to drug or its components

Precautions

Use cautiously in:

• active infections, decreased bone marrow reserve, renal or hepatic impairment

• pregnant patients and patients with childbearing potential

• breastfeeding patients

• children (safety and efficacy not established).

Administration

• For I.V. concentrations above 0.4 mg/ml, mix each 100 mg with 250 to 500 ml of dextrose 5% in water or normal saline solution, to help prevent crystallization.

• Give I.V. infusion over 30 to 60 minutes. Don't use in-line filter.

See Avoid rapid infusion, which may cause severe hypotension and bronchospasm.

• Administer with antiemetics, as prescribed.

• Wear disposable gloves when handling. If drug comes into contact with skin, wash thoroughly with soap and water.

• Be aware that drug is given with other chemotherapeutic agents.

Adverse reactions

CNS: drowsiness, fatigue, headache, vertigo, peripheral neuropathy

CV: hypotension (with I.V. use), heart failure, myocardial infarction

GI: nausea, vomiting, stomatitis

GU: sterility

Hematologic: anemia, leukopenia, thrombocytopenia, bone marrow depression

Hepatic: hepatotoxicity

Metabolic: hyperuricemia

Musculoskeletal: muscle cramps

Respiratory: pulmonary edema, bronchospasm

Other: alopecia, fever, phlebitis at I.V. site, allergic reactions including anaphylaxis

Interactions

Drug-drug. Live-virus vaccines: increased risk of adverse reactions

Other antineoplastics: additive bone marrow depression

Drug-diagnostic tests. Hemoglobin, neutrophils, platelets, red blood cells, white blood cells: decreased values

Uric acid: increased level

Patient monitoring

See Monitor blood pressure during and after infusion. Stop infusion if severe hypotension occurs.

• With I.V. use, monitor infusion rate closely to prevent infusion reactions.

• Throughout infusion, check I.V. site for extravasation, which may cause thrombophlebitis.

See Keep diphenhydramine, hydrocortisone, epinephrine, and artificial airway at hand in case anaphylaxis occurs.

• Assess for CNS adverse effects. Assist patient during ambulation as needed.

See Monitor for signs and symptoms of bone marrow depression.

• Monitor CBC, liver function tests, and blood urea nitrogen and creatinine levels. Report platelet count below 50,000/mm3 or neutrophil count below 500/mm3.

Patient teaching

• Instruct patient to inspect mouth daily for ulcers and bleeding gums.

See Tell patient to immediately report difficulty breathing or signs and symptoms of allergic reaction.

See Caution female of childbearing age to avoid pregnancy and breastfeeding during drug therapy.

• Instruct patient to move slowly when sitting up or standing, to avoid lightheadedness or dizziness from sudden blood pressure decrease.

• Tell patient drug may cause hair loss.

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

etoposide phosphate

(e-toe-poe-side fos-fate ) etoposidephosphate,

Etopophos

(trade name)

Classification

Therapeutic: antineoplastics
Pharmacologic: podophyllotoxin derivatives
Pregnancy Category: D

Indications

Refractory testicular neoplasms (IV only) (used in combination with other chemotherapeutic agents in patients who have already received chemotherapy, surgery, or radiation).Small cell lung carcinoma (PO and IV) (first-line therapy; used in combination with other chemotherapeutic agents).Lymphomas and some leukemias.Uterine cancer.Brain tumors.

Action

Damages DNA before mitosis (cycle-dependent and phase-specific).

Therapeutic effects

Death of rapidly replicating cells, particularly malignant ones.

Pharmacokinetics

Absorption: After IV administration, etoposide phosphate is rapidly converted to etoposide.Distribution: Rapidly distributed; poorly enters the CSF; probably crosses placenta; enters breast milk.Protein Binding: 97%.Metabolism and Excretion: Some metabolism by the liver with biliary excretion, 44% excreted in feces; 45% excreted unchanged by the kidneys.Half-life: 4–11 hr.

Time/action profile (noted as effects on blood counts)

ROUTEONSETPEAKDURATION
IVunknown12–19 days (granulocytes) 10–15 days (platelets)21 days

Contraindications/Precautions

Contraindicated in: Hypersensitivity; Obstetric / Lactation: Pregnancy and lactation; Known intolerance to dextran.Use Cautiously in: Obstetric: Patients with childbearing potential; Active infections; ↓ bone marrow reserve; Renal/hepatic impairment (dosage modification may be necessary); Hypoalbuminemia; Geriatric: May be at ↑ risk of adverse effects; Pediatric: Safety and effectiveness not established; Other chronic debilitating illnesses.

Adverse Reactions/Side Effects

Central nervous system

  • malaise (most frequent)
  • dizziness

Cardiovascular

  • hypertension
  • hypotension

Gastrointestinal

  • anorexia (most frequent)
  • mucositis (most frequent)
  • nausea (most frequent)
  • vomiting (most frequent)
  • abdominal pain
  • constipation
  • diarrhea
  • taste alteration

Dermatologic

  • stevens-johnson syndrome (life-threatening)
  • alopecia (most frequent)
  • pruritis
  • rash
  • urticaria

Endocrinologic

  • sterility

Hematologic

  • anemia (life-threatening)
  • leukopenia
  • thrombocytopenia (life-threatening)

Local

  • phlebitis at IV site

Miscellaneous

  • allergic reactions including anaphylaxis (life-threatening)
  • fever

Interactions

Drug-Drug interaction

↑ bone marrow depression with other antineoplastics or radiation therapy.May alter immune response to live-virus vaccines and ↑ risk of adverse reactions.

Route/Dosage

Other regimens are used. Dosages below are (and should always be) expressed as the desired etoposide dosage).Testicular NeoplasmsIntravenous (Adults) Dosage ranges from 50–100 mg/m2 daily for 5 days up to 100 mg/m2 daily on days 1, 3, and 5; repeat at 3–4 wk intervals.Small-Cell Carcinoma of the LungIntravenous (Adults) Dosage ranges from 35 mg/m2 daily for 4 days up to 50 mg/m2 daily for 5 days; repeat at 3–4 wk intervals.

Availability

Powder for injection: 100 mg/vial (with dextran)

Nursing implications

Nursing assessment

  • Monitor BP before and every 15 min during infusion. If hypotension occurs, stop infusion and notify health care professional. After stabilizing BP with IV fluids and supportive measures, infusion may be resumed at slower rate.
  • Monitor for hypersensitivity reaction (fever, chills, dyspnea, pruritus, urticaria, bronchospasm, tachycardia, hypotension). If these occur, stop infusion and notify health care professional. Keep epinephrine, an antihistamine, corticosteroids, volume expanders, and resuscitative equipment close by in the event of an anaphylactic reaction.
  • Assess for signs of infection (fever, chills, cough, hoarseness, lower back or side pain, sore throat, difficult or painful urination). Notify health care professional if these symptoms occur.
  • Assess for bleeding (bleeding gums, bruising, petechiae, guaiac test stools, urine, and emesis). Avoid IM injections and taking rectal temperatures. Apply pressure to venipuncture sites for 10 min.
  • Monitor intake and output, appetite, and nutritional intake. Etoposide causes mild-to-moderate nausea and vomiting. Prophylactic antiemetics may decrease frequency and duration of nausea and vomiting.
  • Adjust diet as tolerated to help maintain fluid and electrolyte balance and nutritional status.
  • Assess for rash periodically during therapy. May cause Stevens-Johnson syndrome. Discontinue therapy if severe or if accompanied with fever, general malaise, fatigue, muscle or joint aches, blisters, oral lesions, conjunctivitis, hepatitis and/or eosinophilia.
  • Lab Test Considerations: Monitor CBC and differential before, prior to each cycle of therapy and periodically during therapy. The nadir of leukopenia occurs in 15–22, days, granulocytopenia in 12–19 days, and. and thrombocytopenia in 10–15 days after initiation of therapy. Bone marrow recovery usually occurs by day 21, but may be delayed. If absolute neutrophil count is <500/mm3 or platelet count is <50,000/mm3, hold therapy until blood counts have recovered sufficiently.
    • Monitor liver function studies (AST, ALT, LDH, bilirubin) and renal function studies (BUN, creatinine) before and periodically during therapy to detect hepatotoxicity and nephrotoxicity.

Potential Nursing Diagnoses

Risk for injury (Side Effects)
Risk for infection (Side Effects)

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.
  • Do not confuse etoposide (VePesid) with etoposide phosphate (Etopophos).
  • Solution should be prepared in a biologic cabinet. Wear gloves, gown, and mask while handling medication. Discard equipment in designated containers.
    • Avoid contact with skin. Use Luer-Lok tubing to prevent accidental leakage. If contact with skin occurs, immediately wash skin with soap and water.
  • Intravenous Administration
  • pH: 2.9.
  • Intermittent Infusion: Reconstitute each vial with 5 or 10 mL of sterile water, D5W, or 0.9% NaCl for a concentration of 20 or 10 mg/mL, respectively.
    • Diluent: May be administered undiluted or diluted with D5W or 0.9% NaCl. Concentration: as low as 0.1 mg/mL.
    • Reconstituted solutions are stable for 24 hr at room temperature or for 7 days if refrigerated.
  • Rate: Administer over 5–210 min. Do not administer as a bolus injection.
  • Y-Site Compatibility: acyclovir, alemtuzumab, alfentanil, amifostine, amikacin, aminocaproic acid, aminophylline, amiodarone, ampicillin, ampicillin/sulbactam, anidulafungin, argatroban, atracurium, aztreonam, bivalirudin, bleomycin, bumetanide, buprenorphine, butorphanol, calcium acetate, calcium chloride, calcium gluconate, carboplatin, carmustine, caspofungin, cefazolin, cefoperazone, cefotaxime, cefotetan, cefoxitin, ceftazidime, ceftriaxone, cefuroxime, chloramphenicol, ciprofloxacin, cisatracurium, cisplatin, clindamycin, cyclophosphamide, cyclosporine, cytarabine, dacarbazine, dactinomycin, daptomycin, daunorubicin hydrochloride, dexamethasone, dexmedetomidine, dexrazoxane, digoxin, diltiazem, diphenhydramine, dobutamine, docetaxel, dopamine, doripenem, doxicurium, doxorubicin, doxycycline, enalaprilat, ephedrine, epinephrine, epirubicin, ertapenem, erythromycin, esmolol, famotidine, fenoldopam, fentanyl, floxuridine, fluconazole, fludarabine, fluorouracil, foscarnet, fosphenytoin, furosemide, ganciclovir, gemcitabine, gentamicin, glycopyrrolate, granisetron, haloperidol, heparin, hydralazine, hydrocortisone, hydromorphone, idarubicin, ifosfamide, insulin, irinotecan, isoproterenol, ketorolac, labetalol, leucovorin calcium, levofloxacin, levorphanol, lidocaine, linezolid, lorazepam, magnesium sulfate, mannitol, mechlorethamine, meperidine, meropenem, mesna, metaraminol, methotrexate, methyldopate, metoclopramide, metoprolol, metronidazole, midazolam, milrinone, mitoxantrone, morphine, nafcillin, nalbuphine, naloxone, nesiritide, nitroglycerine, nitroprusside, norepinephrine, octreotide, ondansetron, oxaliplatin, paclitaxel, palonosetron, pamidronate, pancuronium, pemetrexed, pentamidine, pentazocine, pentobarbital, phenobarbital, phentolamine, phenylephrine, piperacillin/tazobactam, potassium acetate, potassium chloride, potassium phosphates, procainamide, promethazine, propranolol, quinupristin/dalfopristin, ranitidine, remifentanil, rituximab, rocuronium, sodium acetate, sodium bicarbonate, sodium phosphates, streptozocin, succinylcholine, sufentanil, tacrolimus, teniposide, theophylline, thiopental, thiotepa, ticarcillin/clavulanate, tigecycline, tirofiban, tobramycin, tolazoline, trastuzumab, trimethoprim/sulfamethoxazole, vancomycin, vecuronium, verapamil, vinblastine, vincristine, vinorelbine, voriconizole, zidovudine, zoledronic acid
  • Y-Site Incompatibility: allopurinol, amphotericin B colloidal, amphotericin B lipid complex, amphotericin B liposome, cefepime, chlorpromazine, dantrolene, diazepam, imipenem/cilastatin, methohexital, methylprednisolone, mitomycin, pantoprazole, phenytoin, prochlorperazine

Patient/Family Teaching

  • Explain the purpose of etoposide phosphate to patient.
  • Advise patient to notify health care professional if fever; chills; sore throat or other signs of infection; bleeding gums; bruising; petechiae; or blood in urine, stool, or emesis occurs. Caution patient to avoid crowds and persons with known infections. Instruct patient to use soft toothbrush and electric razor. Caution patient not to drink alcoholic beverages or take products containing aspirin or NSAIDs.
  • Instruct patient to notify health care professional if rapid heartbeat, difficulty breathing, abdominal pain, yellow skin/eyes, weakness, paresthesia, or gait disturbances occur.
  • Instruct patient to inspect oral mucosa for redness and ulceration. If mouth sores occur, advise patient to use sponge brush and rinse mouth with water after eating and drinking. Viscous lidocaine swishes may be used if pain interferes with eating. Stomatitis pain may require treatment with opioid analgesics.
  • Discuss with patient the possibility of hair loss. Explore coping strategies.
  • Instruct patient not to receive any vaccinations without advice of health care professional.
  • Advise patient to use contraception.
  • Emphasize the need for periodic lab tests to monitor for side effects.

Evaluation/Desired Outcomes

  • Decrease in size or spread of malignancies in solid tumors.