Etopul

Each 5 mL ampule contains Etoposide, USP 100 mg.

Pharmacology: Pharmacodynamics: Etoposide is a semi-synthetic podophyllotoxin derivative. Its main effect seems to occur during the G₂ phase of the cell cycle. Two dose-dependent reactions occur: At high concentrations (>10 μg/mL), lysis can be observed of the cells entering mitosis; at low concentrations (0.3-10 μg/mL), the cells are prevented from entering the prophase. The main macromolecular effect appears to be inhibition of DNA synthesis.
Pharmacokinetics: Following administration by mouth absorption is variable, but on average about 50% of the dose of etoposide is absorbed. The pharmacokinetics of etoposide are subject to considerable interindividual variation. It is rapidly distributed, and concentrations in plasma fall in a biphasic manner, with a terminal half-life of 3 to 19 hours. It is extensively bound to plasma protein (about 94%). Etoposide is excreted in urine and feces as unchanged drug and metabolites: about 45% of a dose is reported to be excreted in urine over 72 hours, two-thirds as unchanged drug. It crosses the blood-brain barrier poorly, with concentrations in CSF from 1 to 10% of those in plasma.

Small cell lung carcinoma, lymphosarcoma, acute leukemia, testicular tumor and bladder cancer.

The recommended course of etoposide Injection is 60-100 mg/m², IV, daily for five consecutive days. As etoposide produces myelosuppression, courses may not be repeated more frequently than at 3 weeks intervals.
The dosage may vary according to the symptom.
Immediately before administration, the required dose of etoposide Injection must be diluted with 0.9% saline solution for injection to give a solution concentration of not more than 0.25 mg/mL of etoposide; it should then be given by intravenous infusion over a period of not less than 30 minutes. Care should be taken to avoid extravasation.

Overdose can lead within one-two weeks to severe myelosuppression. Total doses of 2.4-3.5 g/m² of etoposide administered intravenously over 3 days have caused mucositis and myelotoxicity. Metabolic acidosis and severe hepatic toxicity have been reported after the administration of doses that were higher than recommended. There is no specific antidote available. Treatment should therefore be symptomatic and supportive, and patients should be closely monitored.

Etoposide is contraindicated in the following patients: Patients with severe bone marrow depression; severe hypersensitivity to this drug.
Since etoposide drug contains benzyl alcohol, it is contraindicated in neonates, prematures.

Etoposide should be administered with caution in the following patients: Patients with bone marrow depression.
Patients with hepatic impairment, cardiac impairment, patients who have a complication of infection, chickenpox (fatal systemic symptom may appear).
Severe adverse reaction including bone marrow depression may occur. Therefore, monitor patient’s condition and perform clinical tests (hematologic, hepatic, renal test) frequently. If any symptoms occur, the dose of the drug should be reduced or the drug should be discontinued and appropriate corrective measures should be taken.
Since long-term therapy may cause serious adverse reaction or become chronic, the administration should be cautioned.
Manifestation or ingravescence of bleeding tendency should be cautioned.
Use in pediatric should be especially considered about manifestation of adverse reaction and the administration cautioned.
In use in children or patients of child bearing age, the influence on gonad should be considered.
Etoposide should not be administered subcutaneously or intramuscularly.
IV administration may cause vascular pain, phlebitis, hypotension, arrhythmia, therefore, injection site and administration method should be considered. And rate of injection should be as slow as possible.
When etoposide is administered intravenously, care should be taken to avoid extravasation.
Etoposide should be diluted to the concentration of not more than 0.25 mg/mL to avoid precipitation. The reconstituted solution should be used immediately after reconstitution.
Others: In the treatment of acute leukemia, peripheral vessel and bone marrow should be regularly monitored and also period of the administration should be reduced or prolonged.
In animal studies, the drug has been excreted in milk. Use in nursing mothers should be avoided.
Use in the Elderly: No dosage adjustment is necessary among the elderly.
Use in Children: Use in children should be especially considered because of the possibility of occurrence of adverse reactions. Safety and effectiveness in children have not been established.
Use in Pregnancy and Lactation: In animal studies, teratogenesis has been reported. Therefore, the drug should not be administered to pregnant women or women suspected of being pregnant.

In animal studies, teratogenesis has been reported. Therefore, the drug should not be administered to pregnant women or women suspected of being pregnant.

Hematological: Leukopenia, thrombocytopenia, bleeding, and anemia may occur.
Hepatic: Hepatic function disorder such as elevations of GOT, GPT, ALP may occur.
Renal: Elevations of BUN, creatinine may occur.
Gastrointestinal: Nausea, vomiting, anorexia, stomatitis, diarrhea, abdominal pain, and constipation may occur.
Hypersensitivity: Rash may occur.
Dermatologic: Severe alopecia, erythema, pruritus may occur.
Nervous System: carpopedal numbness, headache may occur.
Respiratory: Occasionally, ECG abnormality, arrhythmia, hypotension may occur.
Others: Malaise, flush may occur. Adverse effects including bone marrow depression may vary by concomitant administration with other antineoplastic agents or radiotherapy.

The co-administration of high doses of cyclosporine (serum concentration >2000 ng/mL) and oral etoposide led to AUC values for etoposide that were elevated by 80% and to clearance that was reduced by 38% in comparison with etoposide monotherapy.
Concomitant treatment with cisplatin is associated with reduced total body clearance of etoposide. Concomitant phenytoin or phenobarbital therapy is associated with increased etoposide clearance and reduced efficacy.
Prior or concurrent use of other drugs with similar myelosuppression action as etoposide may be expected to have additive or synergetic effects.
There is increased risk of fatal systemic vaccinal disease with the use of yellow fever vaccine. Live vaccines are contraindicated in immunosuppressed patients.
In vitro, plasma protein binding is 97%. Phenylbutazone, sodium salicylate, and acetylsalicylic acid may displace etoposide from plasma protein binding. Concomitant warfarin therapy may result in elevated international normalized ratio (INR). Close monitoring of INR is recommended.
Cross resistance between anthracyclines and etoposide has been reported in preclinical experiments.

Etoposide should not be used without diluting. Dilute with 0.9% sodium chloride or 5% dextrose. Solutions showing any signs of precipitation should not be used.
For waste-disposal and safety information guidelines on safe-handling of antineoplastic drugs should be followed. Any contact with the fluid should be avoided. During preparation and reconstitution a strictly aseptic working technique should be used; protective measures should include the use of gloves, mask, safety goggles and protective clothing. Use of a vertical laminar airflow (LAF) hood is recommended.
Gloves should be worn during administration. Waste-disposal procedures should take into account the cytotoxic nature of this substance.
If etoposide contacts skin, mucosae or eyes, immediately wash thoroughly with water. Soap may be used for skin cleansing.
Precaution in Administration: Etoposide should be diluted to the concentration of not more than 0.25 mg/mL to avoid precipitation. The reconstituted solution should be used immediately after reconstitution.

Store at temperatures not exceeding 30°C.

Cytotoxic Chemotherapy

L01CB01 - etoposide ; Belongs to the class of plant alkaloids and other natural products, podophyllotoxin derivatives. Used in the treatment of cancer.

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