etoposide phosphate

e-toe-POE-side FOS-fate

Therapeutic Classification: antineoplastics

Pharmacologic Classification: podophyllotoxin derivatives

High Alert

Refractory testicular neoplasms (in combination with other chemotherapy agents).
First-line therapy of small cell lung cancer (in combination with other chemotherapy agents).

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

Therapeutic effects:

Death of rapidly replicating cells, particularly malignant ones.

Absorption: After IV administration, etoposide phosphate is rapidly converted to etoposide.

Distribution: Rapidly distributed to tissues; poorly enters the CSF.

Protein Binding: 97%.

Metabolism/Excretion: Some metabolism by the liver with biliary excretion. 44% excreted in feces; 45% excreted unchanged by the kidneys.

Half-Life: 4–11 hr.

(effects on blood counts)

ROUTE	ONSET	PEAK	DURATION
IV	unknown	12–19 days (granulocytes); 10–15 days (platelets)	21 days

Contraindicated in:

Hypersensitivity;
Known intolerance to dextran;
OB: Pregnancy;
Lactation: Lactation.

Use Cautiously in:

;
Active infection;
↓bone marrow reserve;
Hypoalbuminemia;
Renal impairment (dosage modification may be necessary);
Hepatic impairment (dosage modification may be necessary);
Rep: Women of reproductive potential and men with female partners of reproductive potential;
Pedi: Safety and effectiveness not established in children;
Geri: Older adults may be at ↑ risk of adverse effects.

CV: hypertension, hypotension

Derm: alopecia, pruritus, rash, STEVENS-JOHNSON SYNDROME (SJS), urticaria

Endo: infertility

GI: anorexia, mucositis, nausea, vomiting, abdominal pain, constipation, diarrhea

Hemat: leukopenia, ANEMIA, THROMBOCYTOPENIA

Local: phlebitis at IV site

Neuro: malaise, dizziness, dysgeusia

Misc: fever, HYPERSENSITIVITY REACTIONS (INCLUDING ANAPHYLAXIS)

Drug-drug:

↑risk of bone marrow depression with other antineoplastics or radiation therapy.
May alter immune response to live-virus vaccines and ↑ risk of adverse reactions.
Phenytoin, phenobarbital, carbamazepine, and valproic acid may ↓ levels and effectiveness.
May ↑ risk of bleeding with warfarin.

Doses below are (and should always be) expressed as the desired etoposide dose).

Testicular Neoplasms

IV (Adults ): 50–100 mg/m² once daily on Days 1–5 of each 21–day or 28–day cycle OR100 mg/m² once daily on Days 1, 3, and 5 of each 21–day or 28–day cycle.

Renal Impairment

IV (Adults ): CCr 15–50 mL/min: Administer 75% of recommended dose.

Small-Cell Carcinoma of the Lung

IV (Adults ): 35 mg/m² once daily for 4 days of each 21–day or 28–day cycle OR50 mg/m² once daily for 5 days of each 21–day or 28–day cycle. Adjuvant therapy for limited-stage disease, initiated within 8 wk of resection, should consist of 4 cycles of etoposide plus cisplatin or carboplatin. For extensive-stage disease, 4 to 6 cycles of chemotherapy are recommended

Renal Impairment

IV (Adults ): CCr 15–50 mL/min: Administer 75% of recommended dose.

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

Monitor BP before and every 15 min during infusion. If hypotension occurs, stop infusion and notify health care provider. After stabilizing BP with IV fluids and supportive measures, resume infusion at slower rate.
Monitor for signs/symptoms of hypersensitivity reactions (rash, urticaria, pruritus, flushing, tachycardia, dizziness, vomiting, hypotension). If reaction occurs, discontinue etoposide phosphate and provide supportive care. Keep epinephrine, an antihistamine, corticosteroids, volume expanders, and resuscitative equipment close by in the event of an anaphylactic reaction.
Assess for signs/symptoms of infection (fever, chills, cough, hoarseness, lower back or flank pain, sore throat, difficult or painful urination). Notify health care provider if these symptoms occur.
Monitor for signs/symptoms of bleeding or hemorrhage such as weakness, tachycardia, dyspnea, dizziness, pallor, petechiae, fatigue, tarry stools, coffee ground emesis or epistaxis. Avoid IM injections and taking rectal temperatures. Apply pressure to venipuncture sites for 10 min.
Monitor intake and output, appetite, and nutritional intake. Etoposide phosphate causes mild-to-moderate nausea and vomiting. Prophylactic antiemetics may ↓ 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 SJS. If reaction occurs, discontinue etoposide phosphate 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:

Verify negative pregnancy test before starting therapy.
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 ANC <500/mm³ or platelet count <50,000/mm³, hold etoposide phosphate until blood counts have recovered sufficiently.
- Monitor liver function (AST, ALT, LDH, bilirubin) and renal function (BUN, creatinine) before and periodically during therapy.

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.
Etoposide phosphate should be administered under the supervision of a qualified physician experienced in the use of cancer chemotherapeutic agents . Severe myelosuppression with resulting infection or bleeding may occur.
Do not confuse etoposide with etoposide phosphate.
When preparing, wear double chemotherapy gloves, protective gown, respiratory (N95) protection, and hair and shoe covers; optimally prepare in a ventilated control device. When administering, add eye/face protection if there is a potential that the substance could splash. Use a closed system drug-transfer device when dosage form allows. Single chemotherapy gloves are appropriate if administering from prefilled syringe or injector. Discard IV equipment in specially designated containers.
- Healthcare providers who are actively trying to conceive, who are pregnant or may become pregnant, and who are breastfeeding should avoid handling etoposide phosphate.
- Avoid contact with skin. Use Luer-Lok tubing to prevent accidental leakage. If contact with skin occurs, immediately wash skin with soap and water.

IV Administration:

Intermittent Infusion: Reconstitution: Reconstitute each vial with 5 or 10 mL of sterile water, D5W, or 0.9% NaCl, respectively. Reconstituted solutions are stable for 24 hr at room temperature or for 7 days if refrigerated.Concentration: 20 mg/mL (with 5 mL); 10 mg/mL (with 10 mL).
- Diluent: May be administered undiluted or diluted with D5W or 0.9% NaCl. Concentration: as low as 0.1 mg/mL.
Rate: Administer over 5–210 min. Do not administer as a bolus injection.
Y-Site Compatibility:
- acyclovir
- alemtuzumab
- amifostine
- amikacin
- aminocaproic acid
- aminophylline
- amiodarone
- ampicillin
- ampicillin/sulbactam
- anidulafungin
- argatroban
- arsenic trioxide
- atracurium
- azithromycin
- aztreonam
- bivalirudin
- bleomycin
- bumetanide
- buprenorphine
- butorphanol
- calcium acetate
- calcium chloride
- calcium gluconate
- carboplatin
- carmustine
- caspofungin
- cefazolin
- cefotaxime
- cefotetan
- cefoxitin
- ceftazidime
- ceftriaxone
- cefuroxime
- chloramphenicol
- ciprofloxacin
- cisatracurium
- cisplatin
- clindamycin
- cyclophosphamide
- cyclosporine
- cytarabine
- dacarbazine
- dactinomycin
- daptomycin
- daunorubicin
- dexamethasone
- dexmedetomidine
- dexrazoxane
- digoxin
- diltiazem
- diphenhydramine
- dobutamine
- docetaxel
- dopamine
- doxorubicin hydrochloride
- doxorubicin liposomal
- doxycycline
- enalaprilat
- ephedrine
- epinephrine
- epirubicin
- ertapenem
- erythromycin
- esmolol
- famotidine
- fentanyl
- floxuridine
- fluconazole
- fludarabine
- fluorouracil
- foscarnet
- fosphenytoin
- furosemide
- ganciclovir
- gemcitabine
- gentamicin
- glycopyrrolate
- granisetron
- haloperidol
- heparin
- hydralazine
- hydrocortisone
- hydromorphone
- idarubicin
- ifosfamide
- insulin, regular
- irinotecan
- isoproterenol
- ketorolac
- labetalol
- leucovorin
- levofloxacin
- levorphanol
- lidocaine
- linezolid
- lorazepam
- magnesium sulfate
- mannitol
- meperidine
- meropenem
- mesna
- methadone
- methotrexate
- metoclopramide
- metoprolol
- metronidazole
- midazolam
- milrinone
- mitoxantrone
- morphine
- moxifloxacin
- nafcillin
- nalbuphine
- naloxone
- nicardipine
- nitroglycerin
- nitroprusside
- norepinephrine
- octreotide
- ondansetron
- oxaliplatin
- paclitaxel
- palonosetron
- pamidronate
- pemetrexed
- pentamidine
- pentobarbital
- phenobarbital
- phentolamine
- phenylephrine
- piperacillin/tazobactam
- potassium acetate
- potassium chloride
- potassium phosphates
- procainamide
- promethazine
- propranolol
- remifentanil
- rituximab
- rocuronium
- sodium acetate
- sodium bicarbonate
- sodium phosphates
- succinylcholine
- sufentanil
- tacrolimus
- theophylline
- thiotepa
- tigecycline
- tirofiban
- tobramycin
- topotecan
- trastuzumab
- trimethoprim/sulfamethoxazole
- vancomycin
- vasopressin
- vecuronium
- verapamil
- vinblastine
- vincristine
- vinorelbine
- voriconazole
- zidovudine
- zoledronic acid
Y-Site Incompatibility:
- allopurinol
- amphotericin B deoxycholate
- amphotericin B liposomal
- cefepime
- chlorpromazine
- dantrolene
- diazepam
- gemtuzumab ozogamicin
- imipenem/cilastatin
- methohexital
- methylprednisolone
- mitomycin
- pantoprazole
- phenytoin
- prochlorperazine

Explain the purpose and side effects of etoposide phosphate to patient. Do not stop receiving drug without consulting health care provider. If an appointment is missed, reschedule as soon as possible. Advise patient to read Patient Information before starting and periodically during therapy in case of changes.
Explain need for continued medical follow-up to monitor progress and assess effectiveness and possible side effects of medication. Periodic lab tests will be needed.
Advise patient to notify health care professional if fever; chills; sore throat or other signs/symptoms of infection. Caution patient to avoid crowds and persons with known infections.
Tell patient to report and seek treatment for signs/symptoms of bleeding such as weakness, fast heart beat, trouble breathing, dizziness, pale skin, tiredness, obvious bleeding in urine, stool, mouth, gums, or nose. Instruct patient to use soft toothbrush and electric razor. Caution patient not to drink alcoholic beverages or take products containing aspirin or NSAIDs.
Advise patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult with health care professional before taking other medications.
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.
Rep: May cause fetal harm. Advise women of reproductive potential to avoid pregnancy and breastfeeding during therapy during therapy. May cause infertility, premature menopause, and amenorrhea in women; recovery of menses and ovulation is related to age at treatment. May result in oligospermia, azoospermia, and permanent loss of fertility in men; may also damage spermatozoa and testicular tissue, resulting in possible genetic fetal abnormalities. Advise women of reproductive potential to use effective contraception during therapy and for ≥6 mo after final dose. Men with female sexual partners of reproductive potential should use condoms during therapy and for ≥4 mo after final dose.

Decrease in size or spread of malignancies in solid tumors.

Etopophos

section name header

Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇

Time/Action Profile ⬆ ⬇

Contraind./Precautions ⬆ ⬇

Adv. Reactions/Side Effects ⬆ ⬇

Interactions ⬆ ⬇

Route/Dosage ⬆ ⬇

Availability ⬆ ⬇

Assessment ⬆ ⬇

Implementation ⬆ ⬇

Patient/Family Teaching ⬆ ⬇

Evaluation/Desired Outcomes ⬆ ⬇

US Brand Names ⬆