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All about: Etoposide

Big Image Pronouncation: (EH-toe-POE-side)
Class: Podophyllotoxin derivative

Trade Names:
VePesid
- Concentrate for injection 20 mg/mL
- Liquid-filled capsules for oral use 50 mg

Trade Names:
Toposar
- Concentrate for injection 20 mg/mL
- Liquid-filled capsules for oral use 50 mg

Trade Names:
Etopophos
- Powder for injection 100 mg vial

Mechanism of Action

Pharmacology

Etoposide's main effect appears to be at the G 2 portion of the cell cycle. At high concentrations (10 mcg/mL or more), lysis of cells entering mitosis is seen; at low concentrations (0.3 to 10 mcg/mL), cells are inhibited from entering prophase. Predominant macromolecular effect appears to be DNA synthesis inhibition.

Pharmacokinetics

Absorption

Bioavailability is approximately 50% (oral).

Distribution

Distribution t ½ is approximately 1.5 h. Vd is approximately 18 to 29 L (at steady state). 97% is protein bound.

Metabolism

Etoposide phosphate is rapidly dephosphonylate to etoposide in the plasma. Etoposide is extensively metabolized in the liver (including CYP3A4).

Elimination

The t ½ is approximately 4 to 11 h. Cl is 33 to 48 mL/min. 42 to 67% is excreted in the urine and 0 to 16% is excreted in the feces. Less than 50% is excreted in the urine and less than 6% is excreted in bile as etoposide.

Special Populations

Renal Function Impairment

Total body clearance is reduced, AUC is increased, and Vd is lower.

Indications and Usage

Refractory testicular tumors, small-cell lung cancer.

Unlabeled Uses

Bladder carcinoma, lymphomas, leukemias, Ewing sarcoma, Kaposi sarcoma, brain tumors, gestational trophoblastic tumors, ovarian germ cell tumors, refractory breast tumors, rhabdomyosarcomas, Wilms tumor, bone marrow transplantation.

Contraindications

Standard considerations.

Dosage and Administration

Testicular Cancer
Adults

IV 50 to 100 mg/m 2 /day for 3 to 5 days every 3 to 4 wk.

Small-Cell Lung Cancer
Adults

IV 35 to 50 mg/m 2 /day IV for 4 to 5 days every 3 to 4 wk. PO 2 times the IV dose, rounded to nearest 50 mg, given orally for 21 days. Alternately, 50 mg/m 2 /day orally for 21 days has been given. Repeat regimen after a 1- to 2-wk rest period. Oral bioavailability of the capsules is erratic, averaging 50% (range, 25% to 75%).

Dosage Adjustment
Adults

Hold etoposide if the platelet count is less than 50,000/mm 3 or the absolute neutrophil count is less than 500/mm 3 .

Adjustment in Hepatic Insufficiency
Adults

Dosage reduction may be warranted; specific guidelines are not available.

Adjustment in Renal Insufficiency
Adults

For patients with Ccr of 16 to 50 mL/min, give 75% of the usual dose. Consider further dose reduction for those with Ccr 15 mL/min or less.

General Advice

IV
  • Dilute prior to use with 5% Dextrose or 0.9% Sodium Chloride to final concentration of 0.2 or 0.4 mg/mL. Concentrations less than 0.4 mg/mL may precipitate.
  • Infuse over 30 to 60 min. Do not give by rapid IV injection because of the risk of hypotension.
Extemporaneous oral solution
  • Etoposide solution for injection can be mixed to a final concentration 0.4 mg/mL or less with orange juice, apple juice, or lemonade for oral administration.
  • Stable for 3 h at room temperature.

Storage/Stability

Vials

Store at room temperature. At room temperature, 0.2 mg/mL solution is stable for 96 h, 0.4 mg/mL solution is stable for 48 h.

Capsules

Refrigerate; can be stored at room temperature for 3 mo.

Drug Interactions

Warfarin

Etoposide may increase the hypoprothrombinemic effects of warfarin.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Cardiovascular

Hypotension.

Dermatologic

Alopecia; radiation recall.

GI

Nausea and vomiting; abdominal pain; anorexia; diarrhea; mucositis with high doses or prior radiation to head and neck; elevation of LFTs; hepatocellular necrosis.

Genitourinary

Amenorrhea.

Hematologic

Bone marrow suppression, granulocyte nadir at 7 to 14 days, platelet nadir at 9 to 16 days.

Hypersensitivity

Acute anaphylactoid reaction.

Miscellaneous

Increased risk of acute nonlymphocytic leukemia.

Precautions

Warnings

Myelosuppression

Severe cases with resulting infection or bleeding may occur. Dose-limiting bone marrow suppression is the most significant toxicity.


Monitor

BP

Monitor BP before and after infusion.


Pregnancy

Category D .

Lactation

Undetermined.

Children

Safety and efficacy in children not established.

Anaphylaxis

Anaphylaxis manifested by chills, fever, tachycardia, bronchospasm, dyspnea, facial flushing, hypertension, or hypotension may occur.

Hypotension

Administer by slow IV infusion because hypotension may occur with rapid IV injection.

Extravasation

Can cause local irritation or phlebitis. Refer to your institution-specific protocol.

Overdosage

Symptoms

Bone marrow suppression.

Patient Information

  • Contraceptive measures are recommended during treatment.
  • Notify health care provider of any of the following: fever; chills; rapid heartbeat; difficult breathing.

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