Names and pronunciation
Etopophos
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Drug reference
Etopophos
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Func. class.: Antineoplastic— miscellaneous
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Chem. class.: Semisynthetic podo- phyllotoxin
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ACTION: Inhibits cells from entering mitosis, depresses DNA/RNA synthesis, cell-cycle–specific S and G2; binds to a complex of DNA and topoisomerase II, leading to DNA strand breaks
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USES: Testicular cancer, small cell lung cancer
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Unlabeled uses: Leukemias (ALL, AML), desmoid tumor, gastric/ovarian cancer, bone marrow ablation, Hodgkin’s/ non-Hodgkin’s lymphoma, malignant gli- oma, neuroblastoma, stem cell transplant preparation, trophoblastic disease
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CONTRAINDICATIONS: Preg- nancy, breastfeeding, hypersensitivity Precautions: Children, renal/hepatic disease, gout, neutropenia, thrombocyto- penia, infection, bleeding
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Black Box Warning: Bone marrow de- pression, bleeding, infection; requires an experienced clinician Black Box Warning: Bone marrow de- pression: CBC, differential, platelet count weekly; withhold product if WBC is <500/ mm3 or platelet count is <50,000/mm3; notify prescriber, treatment should be delayed • Nephrotoxicity: BUN; serum uric acid; urine CCr; electrolytes prior to, during therapy; I&O ratio; report fall in urine output to <30 mL/hr; check B/P bid, re- port any significant decrease Black Box Warning: Infection: monitor temperature, fever may indicate begin- ning infection; treat active infection be- fore treatment • Hepatotoxicity: hepatic studies prior to, during therapy (bilirubin, AST, ALT, LDH) as needed or monthly; monitor jaundice of skin and sclera, dark urine, clay-colored stools, itchy skin, abdominal pain, fever, diarrhea Black Box Warning: Bleeding: hematu- ria, guaiac stools, bruising or petechiae, mucosa or orifices q8hr • Effects of alopecia on body image; discuss feelings about body changes • B/P q15min during infusion; if systolic reading <90 mm Hg, discontinue infu- sion, notify prescriber • Buccal cavity q8hr for dryness, sores or ulceration, white patches, oral pain, bleeding, dysphagia • Injection site reaction: monitor site closely for infiltration • Local irritation, pain, burning, discol- oration at injection site • Symptoms indicating severe aller- gic reaction: rash, pruritus, urticaria, purpuric skin lesions, itching, flush- ing, restlessness, coughing, difficulty breathing • Frequency of stools, characteristics: cramping, acidosis • Signs of dehydration: rapid respira- tions, poor skin turgor, decreased urine output, dry skin, restlessness, weakness • Geriatric patients: increased alope- cia, GI effects, infection, nephrotoxicity, myelosuppression Black Box Warning: An experienced cli- nician knowledgeable in the use of cyto- toxic products • Pregnancy/breastfeeding: do not use in pregnancy, breastfeeding unless bene- fits to mother outweigh risk to fetus
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SIDE EFFECTS CNS: Headache, fever, peripheral neu- ropathy, paresthesias, confusion, chills, fever CV: Hypotension, MI, dysrhythmias GI: Nausea, vomiting, anorexia, hep- atotoxicity, dyspepsia, diarrhea, constipation GU: Nephrotoxicity HEMA: Thrombocytopenia, leukopenia, myelosuppression, anemia INTEG: Rash, alopecia, phlebitis at IV site, Stevens-Johnson syndrome RESP: Bronchospasm SYST: Anaphylaxis, secondary malignancy
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INTERACTIONS Increase: bone marrow depression— other antineoplastics, radiation, immuno- suppressives Increase: adverse reactions—live virus vaccines, toxoids Increase: effect of etoposide, toxicity— voriconazole, conivaptan, cycloSPORINE, imatinib, nilotinib, etravirine, telithromycin Increase: risk of bleeding—anticoagu- lants, NSAIDs, platelet inhibitors, throm- bolytics, salicylate Decrease: etoposide effect—sargramos- tim, filgrastim, separate by ≥24 hr Drug/Food • Decreased oral etoposide—grapefruit juice Drug/Lab Test Decrease: platelets, RBC, WBC, neutro- phils, Hb, calcium, phosphate Increase: uric acid, potassium
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DOSAGE AND ROUTES Testicular cancer • Adult: IV 100 mg/m2/day on days 1, 2 in combination with bleomycin and CIS- platin (BEP) or 100 mg/m2/day on days 1, 3, 5, repeat q3-4wk Small cell lung carcinoma first-line treatment with CISplatin • Adult: IV 50 mg/m2/day over 5 min- 3.5 hr 5 days of a 21-day cycle Renal dose • Adult: IV CCr 45-60 mL/min, reduce dose by 15%; CCr 30-44 mL/min, reduce dose by 20%; CCr <30 mL/min, reduce dose by 25% Hepatic dose • Adult: IV/PO total bilirubin 1.5-2.9 mg/dL: reduce dose by 50%; total biliru- bin 3-5 mg/dL: reduce dose by 75%; total bilirubin >5 mg/dL: hold
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Available forms: Injection 20 mg/mL; 100 mg powder for injection, capsules 50 mg
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Administer: • Antiemetic 30-60 min prior to product and prn to prevent vomiting Urate nephropathy • Allopurinol, aggressive alkalinization to maintain uric acid levels • Antispasmodic, EPINEPHrine, cortico- steroids, antihistamines for reactions PO route • Give without regard to food • Increase fluid intake to 2-3 L/day to prevent urate deposits, calculi forma- tion • Refrigerate oral product; do not freeze IV route • Do not use acrylic or ABS plastic de- vices; may crack, leak Intermittent IV INFUSION route (etopo- side) • Use cytotoxic handling procedures, use Luer-Lok fittings to prevent leakage • After diluting 5-mL vial with 100 mg/250 mL or more D5W or NaCl to 0.2- 0.4 mg/mL, infuse over 30-60 min Y-site compatibilities: Acyclovir, alfent- anil, allopurinol, amifostine, amikacin, aminocaproic acid, aminophylline, amiodarone, amphotericin B colloidal, amphotericin B lipid complex, ampho- tericin B liposome, ampicillin, ampicil lin-sulbactam, anidulafungin, atenolol, atracurium, aztreonam, bivalirudin, bleo- mycin, bumetanide, buprenorphine, butorphanol, calcium chloride/gluconate, CARBOplatin, caspofungin, ceFAZolin, cefotaxime, cefoTEtan, cefOXitin, cefTAZi- dime, ceftizoxime, cefTRIAXone, cefurox- ime, chloramphenicol, chlorproMAZINE, cimetidine, ciprofloxacin, cisatracurium, CISplatin, cladribine, clindamycin, codeine, cyclophosphamide, cycloSPO- RINE, cytarabine, DACTINomycin, DAP- TOmycin, DAUNOrubicin, dexametha- sone, dexmedetomidine, dexrazoxane, digoxin, dilTIAZem, diphenhydrAMINE, DOBUTamine, DOCEtaxel, DOPamine, doxacurium, DOXOrubicin, DOXOrubi- cin liposomal, doxycycline, droperidol, enalaprilat, ePHEDrine, EPINEPHrine, epirubicin, ertapenem, erythromycin, esmolol, famotidine, fenoldopam, fen- taNYL, floxuridine, fluconazole, fludara- bine, fluorouracil, foscarnet, fosphenyt- oin, furosemide, ganciclovir, gatifloxacin, gemcitabine, gentamicin, glycopyrrolate, granisetron, haloperidol, heparin, hydrALAZINE, hydrocortisone, HYDRO- morphone, hydrOXYzine, ifosfamide, imipenem-cilastatin, inamrinone, insulin (regular), irinotecan, isoproterenol, ketorolac, labetalol, lansoprazole, leu- covorin, levofloxacin, levorphanol, lido- caine, linezolid, LORazepam, magnesium sulfate, mannitol, mechlorethamine, mel- phalan, meperidine, meropenem, mesna, methohexital, methotrexate, methyldo- pate, methylPREDNISolone, metoclo- pramide, metoprolol, metroNIDAZOLE, micafungin, midazolam, milrinone, minocycline, mitoXANtrone, mivacu- rium, morphine, nafcillin, nalbuphine, naloxone, nesiritide, nitroglycerin, nitroprusside, norepinephrine, NS, octreotide, ofloxacin, ondansetron, oxali- platin, PACLitaxel, palonosetron, pami- dronate, pancuronium, PEMEtrexed, pentamidine, pentazocine, PENTobarbi- tal, PHENobarbital, phenylephrine, piperacillin, piperacillin-tazobactam, polymyxin B, potassium chloride/phos- phates, procainamide, prochlorperazine, promethazine, propranolol, quinupristin- dalfopristin, ranitidine, remifentanil, rocuronium, sargramostim, sodium ace- tate/bicarbonate/phosphates, succinyl- choline, SUFentanil, sulfamethoxazole- trimethoprim, tacrolimus, teniposide, theophylline, thiotepa, ticarcillin, ticarcil- lin-clavulanate, tigecycline, tirofiban, tobramycin, topotecan, trimethobenza- mide, vancomycin, vasopressin, vecuronium, verapamil, vinBLAStine, vin- CRIStine, vinorelbine, voriconazole, zid- ovudine, zoledronic acid Intermittent IV INFUSION route (etoposide phosphate) • Reconstitute each vial with 5 or 10 mL of D5W, 0.9% NaCl for concentrations of 20 mg/mL or 10 mg/mL, respectively; may give diluted or undiluted to concen- trations of as little as 0.1 mg/mL, give over 5-10 min Y-site compatibilities: Acyclovir, alfent- anil, amifostine, amikacin, aminocaproic acid, aminophylline, amiodarone, ampi- cillin, ampicillin-sulbactam, anidulafun- gin, atenolol, atracurium, aztreonam, bivalirudin, bleomycin, bumetanide, buprenorphine, butorphanol, calcium acetate/chloride/gluconate, CARBOpla- tin, carmustine, caspofungin, ceFAZolin, cefonicid, cefoperazone, cefotaxime, cefoTEtan, cefOXitin, cefTAZidime, cefti- zoxime, cefTRIAXone, cefuroxime, chlor- amphenicol, cimetidine, ciprofloxacin, cisatracurium, CISplatin, clindamycin, codeine, cyclophosphamide, cycloSPO- RINE, cytarabine, dacarbazine, DACTINo- mycin, DAPTOmycin, DAUNOrubicin, dexamethasone, digoxin, diltiazem, diphenhydrAMINE, DOBUTamine, DOCEtaxel, DOPamine, doripenem, dox- acurium, DOXOrubicin, HCL/liposome, doxycycline, enalaprilat, ePHEDrine, EPI- NEPHrine, epirubicin, ertapenem, eryth- romycin, esmolol, famotidine, fenoldo- pam, fentaNYL, floxuridine, fluconazole, fludarabine, fluorouracil, foscarnet, fosphenytoin, furosemide, ganciclovir, gatifloxacin, gemcitabine, gentamicin, glycopyrrolate, granisetron, haloperidol, heparin, hydrALAZINE, hydrocortisone, HYDROmorphone, hydrOXYzine, IDAru- bicin, ifosfamide, inamrinone, insulin (regular), irinotecan, isoproterenol, ketorolac, labetalol, leucovorin, levo- floxacin, levorphanol, lidocaine, line- E zolid, LORazepam, magnesium sulfate, mannitol, mechlorethamine, meperidine, meropenem, mesna, metaraminol, meth- otrexate, methyldopate, metoclopramide, metoprolol, metroNIDAZOLE, mid- azolam, milrinone, minocycline, mito- XANtrone, mivacurium, morphine, nafcil- lin, nalbuphine, naloxone, nesiritide, netilmicin, nitroglycerin, nitroprusside, norepinephrine, octreotide, ofloxacin, ondansetron, oxaliplatin, PACLitaxel, palonosetron, pamidronate, pan- curonium, PEMEtrexed, pentamidine, pentazocine, PENTobarbital, PHENobar- bital, phenylephrine, piperacillin, piper- acillin-tazobactam, plicamycin, poly- myxin B, potassium chloride/phosphates, procainamide, promethazine, proprano- lol, quiNIDine, quinupristin-dalfopristin, ranitidine, remifentanil, riTUXimab, rocuronium, sodium acetate/bicarbon- ate/phosphates, streptozocin, succinyl- choline, SUFentanil, sulfamethoxazole- trimethoprim, tacrolimus, teniposide, theophylline, thiopental, thiotepa, ticar- cillin, ticarcillin-clavulanate, tigecycline, tirofiban, tobramycin, tolazoline, trastu- zumab, trimethobenzamide, vancomycin, vasopressin, vecuronium, verapamil, vinBLAStine, vinCRIStine, vinorelbine, voriconazole, zidovudine, zoledronic acid
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Assess:
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Evaluate: • Therapeutic response: decreased tu- mor size, spread of malignancy
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CLINICAL CONSIDERATIONS
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Patient and caregiver information: • To report any changes in breathing or coughing • That hair may be lost during treat- ment; that a wig or hairpiece may make patient feel better; that new hair may be different in color, texture • That metallic taste may occur • Infection: to report symptoms of in- fection (fever, sore throat); to avoid crowds, persons with known infections • To avoid immunizations • Pregnancy/breastfeeding: to notify prescriber if pregnancy is planned or sus- pected; to use reliable contraception dur- ing and for several mo after therapy; to avoid breastfeeding • To take as prescribed (PO), not to double dose • To report signs of infection (flulike symptoms, fever, fatigue, sore throat) • To check B/P, hypotension occurs
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PHARMACOKINETICS Half-life ½-2 hr (initial), terminal 5¼ hr, metabolized in liver, excreted in urine, feces, crosses placental barrier, protein binding 95%
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• Adult: IV 100 mg/m2/day on days 1, 2 in combination with bleomycin and CIS- platin (BEP) or 100 mg/m2/day on days 1, 3, 5, repeat q3-4wk Small cell lung carcinoma first-line treatment with CISplatin
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• Adult: IV 50 mg/m2/day over 5 min- 3.5 hr 5 days of a 21-day cycle Renal dose
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• Adult: IV CCr 45-60 mL/min, reduce dose by 15%; CCr 30-44 mL/min, reduce dose by 20%; CCr <30 mL/min, reduce dose by 25% Hepatic dose
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• Adult: IV/PO total bilirubin 1.5-2.9 mg/dL: reduce dose by 50%; total biliru- bin 3-5 mg/dL: reduce dose by 75%; total bilirubin >5 mg/dL: hold
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