Etoposide Teva Adverse Reactions

Most adverse reactions are reversible if detected early. If severe reactions occur, dosage should be reduced or discontinued and corrective measures should be instituted (see Precautions).
Hematopoietic System: Severe myelosuppression with resulting infection or bleeding may occur; therefore, patients being treated with etoposide must be frequently observed for myelosuppression both during and after therapy. Dose-limiting bone-marrow suppression is the most significant toxicity associated with etoposide therapy. Therefore, the following laboratory studies should be obtained at the start of therapy and prior to each subsequent dose of etoposide: platelet count, hemoglobin and differential white blood cell count. The occurrence of a platelet count below 50,000/mm³ or an absolute neutrophil count below 500/mm³ is an indication to withhold further therapy until blood counts have sufficiently recovered.
Myelosuppression is dose-related and dose-limiting with granulocyte nadirs occurring 7-14 days after drug administration and platelet nadirs occurring 9-16 days after drug administration. Bone marrow recovery is usually complete by day 20, and no cumulative toxicity has been reported. The frequency of hematopoietic system toxicities is as follows: Leukopenia: < 4,000 WBC/mm³ (60-91%), < 1,000 WBC/mm³ (3-17%).
Thrombocytopenia: < 100,000 platelets/mm³ (22-41%), < 50,000 platelets/mm³ (1-20%).
Anemia: (< 33%).
The occurrence of acute leukaemia, which can occur with or without a preleukemic phase, has been reported rarely in patients treated with etoposide in association with other antineoplastic drugs such as bleomycin, cisplatin, ifosfamide and methotrexate.
Hypotension: Etoposide should be given only by slow intravenous infusion (usually over a 30- to 60-minute period), since hypotension has been reported as a possible side effect of rapid intravenous injection.
Gastrointestinal System: Nausea and vomiting are the major gastrointestinal toxicities. The severity of such nausea and vomiting is generally mild to moderate, with treatment discontinuation required in 1% of patients. Nausea and vomiting can usually be controlled with standard antiemetic therapy. The frequency of gastrointestinal toxicities is as follows: nausea/vomiting (31-43%), anorexia (10-13%), diarrhea (1-13%), abdominal pain (<2%), stomatitis (1-6%), hepatic toxicity (<3%), dysphagia, constipation.
Cardiovascular System: Transient hypotension following rapid intravenous administration has been reported in 1% to 2% of patients. It has not been associated with cardiac toxicity or electrocardiographic changes. No delayed hypotension has been noted. To prevent this rare occurrence, it is recommended that etoposide be administered by slow intravenous infusion over a 30- to 60-minute period. If hypotension occurs, it usually responds to cessation of the infusion and administration of fluids or other supportive therapy as appropriate. When restarting the infusion, a slower administration rate should be used.
Hypersensitivity Reactions (see Warnings): Anaphylactic-like reactions characterized by chills, fever, tachycardia, bronchospasm, dyspnea and hypotension have been reported to occur in 0.7% to 2% of patients receiving intravenous etoposide. These reactions have usually responded promptly to the cessation of the infusion and administration of presser agents, corticosteroids, antihistamines or volume expanders as appropriate. One fatal acute reaction associated with bronchospasm has been reported. Hypertension and flushing have also been reported. Blood pressure usually normalizes within a few hours after cessation of the infusion.
Skin: Reversible alopecia, sometimes progressing to total baldness was observed in up to 66% of patients.
Dental Effects: The bone marrow depressant effects of etoposide may result in an increased incidence of microbial infection, delayed healing, and gingival bleeding. Etoposide may also cause stomatitis, which may be associated with considerable discomfort.
Other Adverse Reactions: The following adverse reactions have been infrequently reported: aftertaste, rash, fever, abnormal pigmentation, pruritus, abdominal pain, constipation, dysphagia, transient cortical blindness and a single report of radiation recall dermatitis. There are reports of hepatic toxicity in patients receiving higher doses of etoposide than those recommended. Metabolic acidosis also has been reported in patients receiving these higher doses.