Etoposide Side Effects

Not all side effects for etoposide may be reported. You should always consult a doctor or healthcare professional for medical advice. Side effects can be reported to the FDA here.

For the Consumer

Applies to etoposide: oral capsule, oral capsule liquid filled

In addition to its needed effects, some unwanted effects may be caused by etoposide. In the event that any of these side effects do occur, they may require medical attention.

You should check with your doctor immediately if any of these side effects occur when taking etoposide:

More common
  • Black, tarry stools
  • bleeding gums
  • blood in the urine or stools
  • chest pain
  • chills
  • cough
  • fever
  • painful or difficult urination
  • pale skin
  • pinpoint red spots on the skin
  • shortness of breath
  • sore throat
  • sores, ulcers, or white spots on the lips or in the mouth
  • swollen glands
  • troubled breathing with exertion
  • unusual bleeding or bruising
  • unusual tiredness or weakness
Less common
  • Blurred vision
  • confusion
  • cough
  • difficulty with swallowing
  • dizziness
  • dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position
  • fast heartbeat
  • feeling of warmth
  • headache
  • hives
  • itching
  • nervousness
  • numbness or tingling in the fingers or toes
  • pounding in the ears
  • puffiness or swelling of the eyelids or around the eyes, face, lips, or tongue
  • redness of the face, neck, arms, and occasionally, upper chest
  • skin rash
  • slow or fast heartbeat
  • sweating
  • tightness in the chest
  • wheezing
Rare
  • Bone pain
Incidence not known
  • Abdominal or stomach pain, severe
  • blistering, peeling, or loosening of the skin
  • cough or hoarseness
  • dark urine
  • diarrhea
  • difficult breathing
  • drowsiness
  • joint or muscle pain
  • loss of appetite
  • lower back or side pain
  • muscle tremors
  • nausea or vomiting
  • rapid, deep breathing
  • red, irritated eyes
  • red skin lesions, often with a purple center
  • restlessness
  • seizures
  • stomach cramps
  • yellow eyes or skin

Some of the side effects that can occur with etoposide may not need medical attention. As your body adjusts to the medicine during treatment these side effects may go away. Your health care professional may also be able to tell you about ways to reduce or prevent some of these side effects. If any of the following side effects continue, are bothersome or if you have any questions about them, check with your health care professional:

More common
  • Hair loss or thinning of the hair
  • swelling or inflammation of the mouth
  • weight loss
Incidence not known
  • Bad, unusual, or unpleasant (after) taste
  • change in taste
  • constipation
  • cracked lips
  • general feeling of discomfort or illness
  • heartburn
  • lack or loss of strength
  • pain or burning in the throat
  • sleepiness or unusual drowsiness

For Healthcare Professionals

Applies to etoposide: intravenous powder for injection, intravenous solution, oral capsule

Hematologic

Hematologic toxicity including leukopenia with WBC counts less than 1,000 WBC/mm3 (3% to 17%), or less than 4,000 WBC/mm3 (60% to 91%), thrombocytopenia with platelet counts less than 50,000 platelets/mm3 (1% to 20%), or less than 100,000 platelets/mm3 (22% to 41%), and anemia (up to 33%) have been reported.

Myelosuppression is dose related and dose limiting. Granulocyte nadirs occur 7 to 14 days after drug administration and usually recover within 20 days. Platelet nadirs occur 9 to 16 days after drug administration. Bone marrow recovery is usually complete by the 20th day. No cumulative toxicity has been reported. Fever and infection have been reported in patients with neutropenia.

Acute leukemia (with or without a preleukemic phase) has been reported rarely in patients treated with etoposide in combination with other antineoplastic agents.[Ref]

Etoposide induced leukemia has features distinct from the syndrome of secondary leukemia associated with alkylating agents. The secondary leukemia that may occur in patients receiving etoposide features a shorter latency period; a predominance of monocytic or myelomonocytic features; and frequent cytogenic abnormalities involving 11q23.

In five single-agent studies of etoposide phosphate used in the treatment of a variety of tumor types, WHO grade III or IV leukopenia, and granulocytopenia were reported more frequently among elderly patients.

Elderly patients may also be more sensitive to myelosuppression.

In one study, six of seven patients treated with 60 mg/m2/day dosages for 5 days developed bone marrow suppression. Three of the six patients developed life-threatening leukopenia, two with sepsis, one of which ended in septic death.[Ref]

Gastrointestinal

The severity of nausea and vomiting is generally mild to moderate. This effect can be prevented by the use of oral phenothiazines in most cases, if necessary. Treatment discontinuation is required in approximately 1% of patients.

Elderly patients may be more sensitive to gastrointestinal effects.[Ref]

Gastrointestinal side effects primarily including nausea and vomiting (31% to 43%) have been reported. Abdominal pain (up to 2%), anorexia (10% to 13%), diarrhea (1% to 13%), stomatitis (1% to 6%) and dysphagia have also been reported. Constipation has been reported infrequently. Gastrointestinal toxicities are slightly more frequent after oral administration than after intravenous infusion.[Ref]

Cardiovascular

In one study of 5 day continuous infusion in 17 patients, 2 patients suffered myocardial infarction and one patient suffered congestive failure during treatment.[Ref]

Cardiovascular side effects including transient hypotension following rapid intravenous administration (1% to 2%) has been reported. Transient hypertension, congestive heart failure, and arrhythmias have been reported rarely.[Ref]

Hypersensitivity

Hypersensitivity side effects including anaphylactic-like reactions characterized by chills, fever, tachycardia, bronchospasm, dyspnea and/or hypotension (0.7% to 2%) have been reported. Hypertension and/or flushing have also been reported. Facial/tongue swelling, coughing, diaphoresis, cyanosis, tightness in throat, laryngospasm, back pain and/or loss of consciousness have sometimes occurred in association with the above reactions. An apparent hypersensitivity-associated apnea has been reported rarely. At least one hypersensitivity-associated death has been reported. Rash, urticaria, and/or pruritus have infrequently been reported.[Ref]

At investigational dosages, a generalized pruritic erythematous macropapular rash, consistent with perivasculitis, has been reported.[Ref]

Dermatologic

Dermatologic side effects including reversible alopecia (8% to 66%), sometimes progressing to total baldness, have been reported. Pruritus, phlebitis, hyperpigmentation and radiation recall dermatitis have been reported rarely.[Ref]

In one study of 21 consecutive days of etoposide therapy, alopecia occurred in 11 of the 12 patients at risk for this toxicity (four had pre-existing alopecia, and two were inevaluable due to early death).

Elderly patients may be more sensitive to alopecia.[Ref]

Hepatic

Hepatic toxicity (up to 3%) has generally been reported in patients receiving higher than recommended dosages. One report notes three cases of severe hepatocellular injury induced by standard dosages.[Ref]

Other

Other side effects including aftertaste, fever, dysphagia, transient cortical blindness, and optic neuritis have been reported infrequently. Although the drug is not considered to be vesicant, chemical phlebitis has been reported in association with etoposide infusion.[Ref]

Metabolic acidosis has been reported in patients receiving higher than recommended dosages.[Ref]

Respiratory

Respiratory side effects including a case report of fatal (biopsy-proven) pulmonary toxicity associated with the use of etoposide in a SCLC patient have been reported.[Ref]

General

In five single-agent studies of etoposide phosphate used in the treatment of a variety of tumor types, asthenia was reported more frequently among elderly patients.[Ref]

General side effects including asthenia have been reported.[Ref]

Immunologic

Immunologic side effects including infectious complications have been reported.[Ref]

Elderly patients may be more sensitive to infectious complications.[Ref]

References

1. Pedersen-Bjergaard J Larsen SO Philip P Daugaard G Sigsgaard TC Andersson M Ersboll J Specht L "TWO SUBTYPES OF THERAPY-RELATED LEUKEMIA (MEETING ABSTRACT)" Proc Annu Meet Am Soc Clin Oncol 11: (1992): A845

2. Donatini B, Krupp P "Secondary pre-leukaemia and etoposide." Lancet 338 (1991): 1269

3. Niederle N Ostermann J Achterrath W Lenaz L Schmidt CG "Etoposide in patients with previously untreated non-small-cell lung cancer: a phase I study." Cancer Chemother Pharmacol 28 (1991): 59-62

4. Smith MA, Rubinstein L, Cazenave L, Ungerleider RS, Maurer HM, Heyn R, Khan FM, Gehan E "Report of the Cancer Therapy Evaluation Program monitoring plan for secondary acute myeloid leukemia following treatment with epipodophyllotoxins." J Natl Cancer Inst 85 (1993): 554-8

5. Kobayashi K, Ratain MJ "Pharmacodynamics and long-term toxicity of etoposide." Cancer Chemother Pharmacol 34 Suppl (1994): s64-8

6. Lokich J Corkery J "Phase I study of VP-16-213 (Etoposide) administered as a continuous 5- day infusion." Cancer Treat Rep 65 (1981): 887-9

7. "Multum Information Services, Inc. Expert Review Panel"

8. Kobayashi K Ratain MJ "New perspectives on the toxicity of etoposide." Semin Oncol 19 (1992): 78-83

9. Kudo K, Yoshida H, Kiyoi H, Numata S, Horibe K, Naoe T "Etoposide-related acute promyelocytic leukemia." Leukemia 12 (1998): 1171-5

10. Kumar L "Epipodophyllotoxins and secondary leukaemia." Lancet 342 (1993): 819-20

11. "Product Information. Vepesid (etoposide)." Bristol-Myers Squibb, Princeton, NJ.

12. DeVore R, Higa G, Robbins A, Sarkar M "Protracted infusion of low-dose etoposide (E): preliminary results of a Phase I/II pharmacokinetic (PK) study (Meeting abstract)." Proc Annu Meet Am Soc Clin Oncol 12 (1993): a4491993

13. Whitlock JA Greer JP Lukens JN "Epipodophyllotoxin-related leukemia. Identification of a new subset of secondary leukemia." Cancer 68 (1991): 600-4

14. Pui CH Raimondi SC Crist WM "Secondary leukaemias after epipodophyllotoxins" Lancet 340 (1992): 672-3

15. Aisner J Van Echo DA Whitacre M Wiernik PH "A phase I trial of continuous infusion VP16-213 (etoposide)." Cancer Chemother Pharmacol 7 (1982): 157-60

16. O'Dwyer PJ Weiss RB "Hypersensitivity reactions induced by etoposide." Cancer Treat Rep 68 (1984): 959-61

17. Ogle KM Kennedy BJ "Hypersensitivity reactions to etoposide. A case report and review of the literature." Am J Clin Oncol 11 (1988): 663-5

18. Hainsworth JD Johnson DH Frazier SR Greco FA "Chronic daily administration of oral etoposide--a phase I trial." J Clin Oncol 7 (1989): 396-401

19. Tran A, Housset C, Boboc B, et al "Etoposide (VP 16-213) induced hepatitis. Report of three cases following standard-dose treatments." J Hepatol 12 (1991): 36-9

20. Dajczman E, Srolovitz H, Kreisman H, Frank H "Fatal pulmonary toxicity following oral etoposide therapy." Lung Cancer 12 (1995): 81-6

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