"Sabahaddin Akman, owner of the Istanbul, Turkey, firm Ozay Pharmaceuticals, has pleaded guilty to charges of smuggling misbranded and adulterated cancer treatment drugs into the United States.
Akman pleaded guilty in the U.S. District Court"...
ETOPOPHOS (etoposide phosphate) has been found to be well tolerated as a single agent in clinical studies involving 206 patients with a wide variety of malignancies, and in combination with cisplatin in 60 patients with small cell lung cancer. The most frequent clinically significant adverse experiences were leukopenia and neutropenia.
The incidences of adverse experiences in the table that follows are derived from studies in which ETOPOPHOS (etoposide phosphate) was administered as a single agent. A total of 98 patients received total doses at or above 450 mg/m² on a 5 consecutive day or day 1, 3, and 5 schedule during the first course of therapy.
Summary of Adverse Events Reported With Single-Agent ETOPOPHOS (etoposide phosphate)
Following Course 1 at Total Five Day Doses of ≥ 450 mg/m²
|Percent of Patients|
|Anemia||< 11 g/dL||72|
|< 8 g/dL||19|
|Nausea and/or vomiting||37|
|Chills and/or Fever||24|
Since etoposide phosphate is converted to etoposide, those adverse experiences that are associated with VePesid can be expected to occur with ETOPOPHOS (etoposide phosphate) .
Myelosuppression after ETOPOPHOS (etoposide phosphate) administration is dose related and dose limiting with the leukocyte nadir counts occurring from day 15 to day 22 after initiation of drug therapy, granulocyte nadir counts occurring day 12 to 19 after initiation of drug therapy, and platelet nadirs occurring from day 10 to 15. Bone marrow recovery usually occurs by day 21 but may be delayed, and no cumulative toxicity has been reported. Fever and infection have also been reported in patients with neutropenia. Death associated with myelosuppression has been reported following etoposide administration.
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.
Blood Pressure Changes
In clinical studies, 151 patients were treated with ETOPOPHOS (etoposide phosphate) with infusion times ranging from 30 minutes to 3.5 hours. Sixty-three patients received ETOPOPHOS (etoposide phosphate) as a 5-minute bolus infusion. Four patients experienced one or more episodes of hypertension and eight patients experienced one or more episodes of hypotension, which may or may not be drug related. One episode of hypotension was reported among those patients who received a 5-minute bolus infusion. If clinically significant hypotension or hypertension occurs with ETOPOPHOS (etoposide phosphate) , appropriate supportive therapy should be initiated.
Anaphylactic-type reactions characterized by chills, rigors, tachycardia, bronchospasm, dyspnea, diaphoresis, fever, pruritus, hypertension or hypotension, loss of consciousness, nausea, and vomiting have been reported to occur in 3% (7/245) of all patients treated with ETOPOPHOS (etoposide phosphate) . Facial flushing was reported in 2% and skin rashes in 3% of patients receiving ETOPOPHOS (etoposide phosphate) . These reactions have usually responded promptly to the cessation of the infusion and administration of pressor agents, corticosteroids, antihistamines, or volume expanders as appropriate; however, the reactions can be fatal. Hypertension and/or flushing have also been reported. Blood pressure usually normalizes within a few hours after cessation of the initial infusion.
Anaphylactic-like reactions have occurred during the initial infusion of ETOPOPHOS (see WARNINGS). 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. In addition, an apparent hypersensitivity-associated apnea has been reported.
Rash, urticaria, and/or pruritus have been reported at recommended doses. At investigational doses, a generalized pruritic erythematous maculopapular rash, consistent with perivasculitis, has been reported.
Reversible alopecia, sometimes progressing to total baldness, was observed in up to 44% of patients.
The following adverse reactions have been reported: abdominal pain, aftertaste, constipation, dysphagia, fever, transient cortical blindness, interstitial pneumonitis/pulmonary fibrosis, optic neuritis, pigmentation, seizure (occasionally associated with allergic reactions), Stevens-Johnson syndrome, toxic epidermal necrolysis, and radiation recall dermatitis. Hepatic toxicity may be seen.
Local soft tissue toxicity has been reported following extravasation of ETOPOPHOS (etoposide phosphate) . Infiltration of ETOPOPHOS (etoposide phosphate) may result in swelling, pain, cellulitis, and necrosis including skin necrosis.
The incidences of adverse reactions in the table that follows are derived from multiple databases from studies in 2081 patients when VePesid was used either orally or by injection as a single agent.
|Adverse Drug Effects Observed With Single-Agent VePesid||Percent Range of Reported Incidence|
|Leukopenia ( < 1000/mm³)||3-17|
|Leukopenia ( < 4000/mm³)||60-91|
|Thrombocytopenia ( < 50,000/mm³)||1-20|
|Thrombocytopenia ( < 100,000/mm³)||22-41|
|Nausea and vomiting||31-43|
Read the Etopophos (etoposide phosphate) Side Effects Center for a complete guide to possible side effects
Caution should be exercised when administering ETOPOPHOS (etoposide phosphate) with drugs that are known to inhibit phosphatase activities (e.g., levamisole hydrochloride). High-dose cyclosporin A resulting in concentrations above 2000 ng/mL administered with oral etoposide has led to an 80% increase in etoposide exposure with a 38% decrease in total body clearance of etoposide compared to etoposide alone.
Periodic complete blood counts should be done during the course of ETOPOPHOS (etoposide phosphate) treatment. They should be performed prior to each cycle of therapy and at appropriate intervals during and after therapy.
In patients with impaired renal function, the following initial dose modification should be considered based on measured creatinine clearance:
|Measured Creatinine Clearance||> 50 mL/min||15-50 mL/min|
|etoposide||100% of dose||75% of dose|
Subsequent etoposide dosing should be based on patient tolerance and clinical effect. Equivalent dose adjustments of ETOPOPHOS (etoposide phosphate) should be used.
Data are not available in patients with creatinine clearances < 15 mL/min and further dose reduction should be considered in these patients.
Read the Etopophos Drug Interactions Center for a complete guide to possible interactions
Last reviewed on RxList: 5/12/2011
This monograph has been modified to include the generic and brand name in many instances.
Additional Etopophos Information
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