Etoposid Ebewe

Etoposid Ebewe

etoposide

Manufacturer:

EBEWE Pharma

Distributor:

Maxxcare

Marketer:

Mega Lifesciences
Full Prescribing Info
Contents
Etoposide.
Description
Excipients/Inactive Ingredients: Benzyl alcohol (20 mg/ml), Ethanol 96% (261 mg/ml), Macrogol 300, Polysorbate 80, Citric acid.
Action
Pharmacotherapeutic Group: Antineoplastic agents, plant alkaloids and other natural products, podophyllotoxin derivatives. ATC Code: L01CB01.
Pharmacology: Pharmacodynamics: Mechanism of action: The main effect of etoposide appears to be at the late S and early G2 portion of the cell cycle in mammalian cells. Two dose-dependent responses are seen: At high concentrations (10 μg/ml or more), cells entering mitosis are lysed; at low concentrations (0.3 to 10 μg/ml), cells are inhibited from entering prophase. Microtubule assembly is not affected. The predominant macromolecular effect of etoposide seems to be the rupture of the double strand by an interaction with DNA-topoisomerase II or by the formation of free radicals. Etoposide has been shown to cause metaphase arrest in chick fibroblasts.
Pharmacokinetics: Absorption: After either intravenous infusion or oral capsule administration, the Cmax and AUC values exhibit marked intra- and inter-subject variability.
Distribution: The mean volumes of distribution at steady state range from 18 to 29 liters. Etoposide shows low penetration into the CSF. In vitro, etoposide is highly protein bound (97%) to human plasma proteins.
Etoposide binding ratio correlates directly with serum albumin in cancer patients and normal volunteers (see Precautions). Unbound fraction of etoposide correlates significantly with bilirubin in cancer patients.
Biotransformation: The hydroxyacid metabolite [4' dimethyl-epipodophyllic acid-9-(4,6 0-ethylidene-β-D-glucopyranoside)], formed by opening of the lactone ring, is found in the urine of adults and children. It is also present in human plasma, presumably as the trans isomer. Glucuronide and/or sulfate conjugates of etoposide are also excreted in human urine. In addition, O-demethylation of the dimethoxyphenol ring occurs through the CYP450 3A4 isoenzyme pathway to produce the corresponding catechol.
Elimination: On intravenous administration, the disposition of etoposide is best described as a biphasic process with a distribution half-life of about 1.5 hours and terminal elimination half-life ranging from 4 to 11 hours. Total body clearance values range from 33 to 48 ml/min or 16 to 36 ml/min/m2 and, like the terminal elimination half-life, are independent of dose over a range 100 to 600 mg/m2. After intravenous administration of 14C etoposide (100 to 124 mg/m2), mean recovery of radioactivity in the urine was 56% (45% of the dose was excreted as etoposide) and faecal recovery of radioactivity was 44% of the administered dose at 120 hours.
Linearity/non-linearity: Total body clearance and the terminal elimination half-life are independent of dose over a range 100 to 600 mg/m2. Over the same dose range, the areas under the plasma concentration vs. time curves (AUC) and the maximum plasma concentration (Cmax) values increase linearly with dose.
Renal impairment: Patients with impaired renal function receiving etoposide have exhibited reduced total body clearance, increased AUC and higher steady state volume of distribution (see Dosage & Administration).
Hepatic impairment: In adult cancer patients with liver dysfunction, total body clearance of etoposide is not reduced.
Elderly population: Although minor differences in pharmacokinetic parameters between patients ≤65 years and >65 years of age have been observed, these are not considered clinically significant.
Paediatric population: In children, approximately 55% of the dose is excreted in the urine as etoposide in 24 hours. The mean renal clearance of etoposide is 7 to 10 ml/min/m2 or about 35% of the total body clearance over a dose range of 80 to 600 mg/m2. Etoposide, therefore, is cleared by both renal and nonrenal processes, ie, metabolism and biliary excretion. The effect of renal disease on plasma etoposide clearance is not known in children. In children, elevated SGPT levels are associated with reduced active substance total body clearance. Prior use of cisplatin may also result in a decrease of etoposide total body clearance in children.
An inverse relationship between plasma albumin levels and etoposide renal clearance is found in children.
Gender: Although minor differences in pharmacokinetic parameters between genders have been observed, these are not considered clinically significant.
Drug interactions: In a study of the effects of other therapeutic agents on in vitro binding of 14C etoposide to human serum proteins, only phenylbutazone, sodium salicylate, and aspirin displaced protein-bound etoposide at concentrations generally achieved in vivo (see Interactions).
Toxicology: Preclinical safety data: Chronic toxicity: Anaemia, leucopenia, and thrombocytopenia were observed in rats and mice, while dogs had mild reversible deterioration of liver and kidney functions. The dose multiple (based on mg/m2 doses) for these findings at the no-observed adverse-effect-level in the preclinical studies were ≥ approximately 0.05 times compared to the highest clinical dose. Historically, preclinical species have been more sensitive compared to humans towards cytotoxic agents. Testicular atrophy, spermatogenesis arrest, and growth retardation were reported in rats and mice.
Mutagenicity: Etoposide is mutagenic in mammalian cells.
Reproductive toxicity: In animal studies etoposide was associated with dose-related embryotoxicity and teratogenicity.
Carcinogenic potential: Given its mechanism of action, etoposide should be considered a possible carcinogen in humans.
Indications/Uses
Testicular cancer: Etoposide is indicated in combination with other approved chemotherapeutic agents for the treatment of first line, recurrent or refractory testicular cancer in adults.
Small cell lung cancer: Etoposide is indicated in combination with other approved chemotherapeutic agents for the treatment of small-cell lung cancer in adults.
Hodgkin's lymphoma: Etoposide is indicated in combination with other approved chemotherapeutic agents for the treatment of Hodgkin's lymphoma in adult and paediatric patients.
Non-Hodgkin's lymphoma: Etoposide is indicated in combination with other approved chemotherapeutic agents for the treatment of non-Hodgkin's lymphoma in adult and paediatric patients.
Acute myeloid leukaemia: Etoposide is indicated in combination with other approved chemotherapeutic agents for the treatment of acute myeloid leukaemia in adult and paediatric patients.
Gestational trophoblastic neoplasia: Etoposide is indicated for first line and second line therapy in combination with other approved chemotherapeutic agents for the treatment of high risk gestational trophoblastic neoplasia in adults.
Ovarian cancer: Etoposide is indicated in combination with other approved chemotherapeutic agents for the treatment of non-epithelial ovarian cancer in adults. Etoposide is indicated for the treatment of platinum-resistant/refractory epithelial ovarian cancer in adults.
Dosage/Direction for Use
Etoposide should only be administered and monitored under the supervision of a qualified physician experienced in the use of anti-neoplastic medicinal products (see Precautions).
Adult population: The recommended dose of etoposide in adult patients is 50 to 100 mg/m2/day (etoposide equivalent) on days 1 to 5 or 100 to 120 mg/m2 on days 1, 3, and 5 every 3 to 4 weeks in combination with other medicinal products indicated in the disease to be treated. Dose should be modified to take into account the myelosuppressive effects of other medicinal products in the combination or the effects of prior radiotherapy or chemotherapy (see Precautions) which may have compromised bone marrow reserve.
The doses after the initial dose should be adjusted if neutrophil count is below 500 cells/mm3 for more than 5 days. In addition the dose should be adjusted in case of occurrence of fever, infections, or at a thrombocyte count below 25,000 cells/mm3, which is not caused by the disease. Follow up doses should be adjusted in case of occurrence of grade 3 or 4 toxicities or if renal creatinine clearance is below 50 ml/min. At decreased creatinine clearance of 15 to 50 ml/min a dose reduction by 25% is recommended.
Administration precautions: As with other potentially toxic compounds, caution should be exercised in handling and preparing the solution of etoposide. Skin reactions associated with accidental exposure to etoposide may occur. The use of gloves is recommended. If etoposide solution contacts the skin or mucosa, immediately wash the skin with soap and water and flush the mucosa with water (see Special precautions for disposal and other handling under Cautions for Usage).
Elderly population: No dose adjustment is necessary in elderly patients (age >65 years old), other than based on renal function (see Pharmacology: Pharmacokinetics under Actions).
Paediatric population: Hodgkin's lymphoma; non-Hodgkin's lymphoma; acute myeloid leukaemia: Etoposide in paediatric patients has been used in the range of 75 to 150 mg/m2/day (etoposide equivalent) for 2 to 5 days in combination with other antineoplastic agents. The treatment regimen should be chosen according to the local standard of care.
Ovarian cancer; small cell lung cancer; gestational trophoblastic neoplasia; testicular cancer: The safety and efficacy of etoposide below 18 years of age have not been established. Currently available data are described in Pharmacology: Pharmacokinetics under Actions but no recommendation on a posology can be made.
Renal impairment: In patients with impaired renal function, the following initial dose modification should be considered based on measured creatinine clearance. (See table.)

Click on icon to see table/diagram/image

In patients with creatinine clearance less than 15 ml/min and on dialysis further dose reduction is likely to be required as etoposide clearance is further reduced in these patients (see Precautions).
Subsequent dosing in moderate and severe renal impairment should be based on patient tolerance and clinical effect (see Precautions). Since etoposide and its metabolites are not dialysable, it can be administered pre- and post-haemodialysis (see Overdosage).
Method of administration: Etoposide is administered by slow intravenous infusion (usually over a 30 to 60 minute period) (see Precautions).
For instructions on reconstitution and dilution of the medicinal product before administration, see Special precautions for disposal and other handling under Cautions for Usage.
Overdosage
Total doses of 2.4 g/m2 to 3.5 g/m2 administered intravenously over three days have resulted in severe mucositis and myelotoxicity. Metabolic acidosis and cases of serious hepatic toxicity have been reported in patients receiving higher than recommended intravenous doses of etoposide.
Similar toxicities can be expected with oral formulation.
A specific antidote is not available. Treatment should therefore be symptomatic and supportive, and patients should be closely monitored.
Etoposide and its metabolites are not dialysable.
Contraindications
Hypersensitivity to the active substance or to any of the excipients.
Concomitant use of yellow fever vaccine or other live vaccines is contraindicated in immunosuppressed patients (see Interactions).
Lactation (see Use in Pregnancy & Lactation).
Special Precautions
Etoposide should only be administered and monitored under the supervision of a qualified physician experienced in the use of anti-neoplastic medicinal products.
In all instances where the use of etoposide is considered for chemotherapy, the physician must evaluate the need and usefulness of the medicinal product against the risk of adverse reactions. Most such adverse reactions are reversible if detected early. If severe reactions occur, the medicinal product should be reduced in dose or discontinued and appropriate corrective measures should be taken according to the clinical judgment of the physician. Reinstitution of etoposide therapy should be carried out with caution, and with adequate consideration of the further need for the medicinal product and close attention to possible recurrence of toxicity.
Myelosuppression: Dose limiting bone marrow suppression is the most significant toxicity associated with etoposide therapy.
Fatal myelosuppression has been reported following etoposide administration. Patients being treated with etoposide must be observed for myelosuppression carefully and frequently both during and after therapy.
The following haematological parameters should be measured at the start of therapy and prior to each subsequent dose of etoposide; platelet count, haemoglobin, white blood cell count and differential. If radiotherapy or chemotherapy has been given prior to starting etoposide treatment, an adequate interval should be allowed to enable the bone marrow to recover. Etoposide should not be administered to patients with neutrophil counts less than 1,500 cells/mm3 or platelet counts less than 100,000 cells/mm3, unless caused by malignant disease. Doses subsequent to initial dose should be adjusted if neutrophil count less than 500 cells/mm3 occurs for more than 5 days or is associated with fever or infection, if platelet count less than 25,000 cells/mm3 occurs, if any grade 3 or 4 toxicity develops or if renal clearance is less than 50 ml/min. Severe myelosuppression with resulting infection or haemorrhage may occur.
Bacterial infections should be brought under control before treatment with etoposide.
Secondary leukaemia: The occurrence of acute leukaemia, which can occur with or without myelodysplastic syndrome, has been described in patients that were treated with etoposide containing chemotherapeutic regimens. Neither the cumulative risk, nor the predisposing factors related to the development of secondary leukaemia are known. The roles of both administration schedules and cumulative doses of etoposide have been suggested, but have not been clearly defined. An 11q23 chromosome abnormality has been observed in some cases of secondary leukaemia in patients who have received epipodophyllotoxins. This abnormality has also been in patients developing secondary leukemia after being treated with chemotherapy regimens not containing epipodophyllotoxins and in leukaemia occurring de novo. Another characteristic that has been associated with secondary leukaemia in patients who have received epipodophyllotoxins appears to be a short latency period, with average median time to development of leukaemia being approximately 32 months.
Hypersensitivity: Physicians should be aware of the possible occurrence of an anaphylactic reaction with etoposide, manifested by chills, pyrexia, tachycardia, bronchospasm, dyspnoea and hypotension, which can be fatal. Treatment is symptomatic. Etoposide should be terminated immediately, followed by the administration of pressor agents, corticosteroids, antihistamines, or volume expanders at the discretion of the physician.
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.
Injection site reaction: Injection site reactions may occur during administration of etoposide. Given the possibility of extravasation, it is recommended to closely monitor the infusion site for possible infiltration during medicinal product administration.
Low serum albumin: Low serum albumin is associated with increased exposure to etoposide. Therefore patients with low serum albumin may be at increased risk for etoposide-associated toxicities.
Impaired renal function: In patients with moderate (CrCl = 15 to 50 ml/min), or severe (CrCl <15ml/min) renal impairment undergoing haemodialysis, etoposide should be administered at a reduced dose (see Dosage & Administration). Haematological parameters should be measured and dose adjustments in subsequent cycles considered based on haematological toxicity and clinical effect in moderate and severe renal impaired patients.
Impaired hepatic function: Patients with impaired hepatic function should regularly have their hepatic function monitored due to the risk of accumulation.
Tumour lysis syndrome: Tumour lysis syndrome (sometimes fatal) has been reported following the use of etoposide in association with other chemotherapeutic medicinal products. Close monitoring of patients is needed to detect early signs of tumour lysis syndrome, especially in patients with risk factors such as bulky treatment, sensitive tumours, and renal insufficiency. Appropriate preventive measures should also be considered in patients at risk of this complication of therapy.
Mutagenic potential: Given the mutagenic potential of etoposide, an effective contraception is required for both male and female patients during treatment and up to 6 months after ending treatment. Genetic consultation is recommended if the patient wishes to have children after ending the treatment. As etoposide may decrease male fertility, preservation of sperm may be considered for the purpose of later fatherhood (see Use in Pregnancy & Lactation).
[For injectable products containing FM27 in rubber material, e.g. in removable needle shields or tip caps:] Latex-sensitive individuals: The [name of the affected part of the product, e.g. removable needle shield] of Etoposid Ebewe contains a derivative of natural rubber latex. Although no natural rubber latex is detected in the [name of the affected part of the product], the safe use of Etoposid Ebewe in latex-sensitive individuals has not been studied.
Effects on ability to drive and use machines: No studies on the effects on the ability to drive and use machines have been performed.
Etoposide may cause adverse reactions that affect the ability to drive or use machines such as fatigue, somnolence, nausea, vomiting, cortical blindness, hypersensitivity reactions with hypotension.
Patients who experience such adverse reactions should be advised to avoid driving or using machines.
Use In Pregnancy & Lactation
Women of childbearing potential/contraception in males and females: Women of childbearing potential should use appropriate contraceptive measures to avoid pregnancy during etoposide therapy.
Etoposide has been shown to be teratogenic in mice and rats (see Pharmacology: Toxicology: Preclinical safety data under Actions).
Given the mutagenic potential of etoposide, an effective contraceptive is required for both male and female patients during treatment and up to 6 months after ending treatment (see Precautions). Genetic consultation is recommended if the patient wishes to have children after ending treatment.
Pregnancy: There are no or limited amount of data from the use of etoposide in pregnant women.
Studies in animals have shown reproductive toxicity (see Pharmacology: Toxicology: Preclinical safety data under Actions).
In general etoposide can cause foetal harm when administered to pregnant women.
Etoposide should not be used during pregnancy unless the clinical condition of the woman requires treatment with etoposide.
Women of childbearing potential should be advised to avoid becoming pregnant.
Women of childbearing potential have to use effective contraception during and up to 6 months after treatment.
If this medicinal product is used during pregnancy, or if the patient becomes pregnant while receiving this medicinal product, the patient should be informed of the potential hazard to the foetus.
Breast-feeding: Etoposide is excreted in human milk.
There is the potential for serious adverse reactions in nursing infants from etoposide. A decision must be made whether to discontinue breast-feeding or to discontinue etoposide, taking into account the benefit of breast-feeding for the child and the benefit of therapy for the woman (see Contraindications).
Fertility: As etoposide may decrease male fertility, preservation of sperm may be considered for the purpose of later fatherhood.
Adverse Reactions
Summary of the safety profile: Dose limiting bone marrow suppression is the most significant toxicity associated with etoposide therapy. In clinical studies in which etoposide was administered as a single agent at a total dose of ≥450 mg/m2 the most frequent adverse reactions of any severity were leucopenia (91%), neutropenia (88%), anaemia (72%), thrombocytopenia (23%), asthenia (39%), nausea and/or vomiting (37%), alopecia (33%) and chills and/or fever (24%).
Summary of adverse reactions: The following adverse reactions were reported from etoposide clinical studies and post-marketing experience.
These adverse reactions are presented by system organ class and frequency, which is defined by the following categories: very common (≥1/10), common (≥1/100, <1/10), uncommon (≥1/1,000, <1/100), rare (≥1/10,000, <1/1,000), not known (cannot be estimated from the available data).
Infections and infestations: Common: Infection.
Neoplasms benign, malignant and unspecified (including cysts and polyps): Common: Acute leukaemia.
Blood and the lymphatic system disorders: Very common: Anaemia, leucopenia, myelosuppression*, neutropenia, thrombocytopenia.
Immune system disorders: Common: Anaphylactic reactions**.
Not known: Angioedema, bronchospasm.
Metabolism and nutrition disorders: Not known: Tumour lysis syndrome.
Nervous system disorders: Common: Dizziness.
Uncommon: Neuropathy peripheral.
Rare: Cortical blindness transient, neurotoxicities (e.g., somnolence and fatigue), optic neuritis, seizure***.
Cardiac disorders: Common: Arrhythmia, myocardial infarction.
Vascular disorders: Common: Hypertension, transient systolic hypotension following rapid intravenous administration.
Uncommon: Haemorrhage.
Respiratory, thoracic and mediastinal disorders: Rare: Interstitial pneumonitis, pulmonary fibrosis.
Not known: Bronchospasm.
Gastrointestinal disorders: Very common: Abdominal pain, anorexia, constipation, nausea and vomiting.
Common: Diarrhoea, mucositis (including stomatitis and oesophagitis).
Rare: Dysgeusia, dysphagia.
Hepatobiliary disorders: Very common: Alanine aminotransferase increased, alkaline phosphatase increased, aspartate amino transferase increased, bilirubin increased, hepatotoxicity.
Skin and subcutaneous tissue disorders: Very common: Alopecia, pigmentation.
Common: Pruritus, rash, urticaria.
Rare: Radiation recall dermatitis, Stevens-Johnson syndrome, toxic epidermal necrolysis.
Reproductive system and breast disorders: Not known: Infertility.
General disorders and administration site conditions: Very common: Asthenia, malaise.
Common: Extravasation****, phlebitis.
Rare: Pyrexia.
* Myelosuppression with fatal outcome has been reported.
** Anaphylactic reactions can be fatal.
*** Seizure is occasionally associated with allergic reactions.
**** Postmarketing complications reported for extravasation included local soft tissue toxicity, swelling, pain, cellulitis, and necrosis including skin necrosis.
Description of selected adverse reactions: In the paragraphs as follows the incidences of adverse events, given as the mean percent, are derived from studies that utilised single agent etoposide therapy.
Haematological toxicity: Myelosuppression (see Precautions) with fatal outcome has been reported following administration of etoposide. Myelosuppression is most often dose-limiting. Bone marrow recovery is usually complete by day 20, and no cumulative toxicity has been reported. Granulocyte and platelet nadirs tend to occur about 10 to 14 days after administration of etoposide depending on the way of administration and treatment scheme. Nadirs tend to occur earlier with intravenous administration compared to oral administration. Leucopenia and severe leucopenia (less than 1,000 cells/mm3) were observed in 91% and 17%, respectively, for etoposide. Thrombocytopenia and severe thrombocytopenia (less than 50,000 platelets/mm3) were seen in 23% and 9% respectively, for etoposide. Reports of fever and infection were also very common in patients with neutropenia treated with etoposide. Bleeding has been reported.
Gastrointestinal toxicity: Nausea and vomiting are the major gastrointestinal toxicities of etoposide. The nausea and vomiting can usually be controlled by antiemetic therapy.
Alopecia: Reversible alopecia, sometimes progressing to total baldness, was observed in up to 44% of patients treated with etoposide phosphate.
Hypotension: Transient hypotension following rapid intravenous administration has been reported in patients treated with etoposide and has not been associated with cardiac toxicity or electrocardiographic changes. Hypotension usually responds to cessation of infusion of etoposide and/or other supportive therapy as appropriate. When restarting the infusion, a slower administration rate should be used. No delayed hypotension has been noted.
Hypertension: In clinical studies involving etoposide, episodes of hypertension have been reported. If clinically significant hypertension occurs in patients receiving etoposide, appropriate supportive therapy should be initiated.
Hypersensitivity: Anaphylactic reactions have been reported to occur during or immediately after intravenous administration of etoposide. The role that concentration or rate of infusion plays in the development of anaphylactic reactions is uncertain. Blood pressure usually normalises within a few hours after cessation of the infusion. Anaphylactic reactions can occur with the initial dose of etoposide.
Anaphylactic reactions (see Precautions), manifested by chills, tachycardia, bronchospasm, dyspnoea, diaphoresis, pyrexia, pruritus, hypertension or hypotension, syncope, nausea, and vomiting have been reported to occur in 3% (7 of 245 patients treated with etoposide in 7 clinical studies) of patients treated with etoposide. Facial flushing was reported in 2% of patients and skin rashes in 3%. These reactions have usually responded promptly to the cessation of the infusion and administration of pressor agents, corticosteroids, antihistamines, or volume expanders as appropriate.
Acute fatal reactions associated with bronchospasm have also been reported with etoposide. Apnoea with spontaneous resumption of breathing following cessation of infusion have also been reported.
Metabolic complications: Tumour lysis syndrome (sometimes fatal) has been reported following the use of etoposide in association with other chemotherapeutic medicinal products (see Precautions).
Paediatric population: The safety profile between paediatric patients and adults is expected to be similar.
Drug Interactions
Effects of other medicinal products on the pharmacokinetics of etoposide: High dose ciclosporin, resulting in plasma concentrations above 2000 ng/ml, administered with oral etoposide has led to an 80% increase in etoposide exposure (AUC) with a 38% decrease in total body clearance of etoposide compared to etoposide alone.
Concomitant cisplatin therapy is associated with reduced total body clearance of etoposide.
Concomitant phenytoin therapy is associated with increased etoposide clearance and reduced efficacy, and other enzyme-inducing antiepileptic therapy may be associated with increased etoposide clearance and reduced efficacy.
[For etoposide phosphate containing formulations only]: As etoposide phosphate is converted in vivo to etoposide by phosphorylation, caution should be exercised when administering etoposide phosphate with medicinal products that are known to inhibit phosphatase activity as such combination may reduce efficacy of etoposide phosphate.
In vitro plasma protein binding is 97%. Phenylbutazone, sodium salicylate, and aspirin may displace etoposide from plasma protein binding.
Effect of etoposide on the pharmacokinetics of other medicinal products: Co-administration of antiepileptic medicinal products and etoposide can lead to decreased seizure control due to pharmacokinetic interactions between the medicinal products.
Co-administration of warfarin and etoposide may result in elevated international normalized ratio (INR). Close monitoring of INR is recommended.
Pharmacodynamic interactions: There is increased risk of fatal systemic vaccinal disease with the use of yellow fever vaccine. Live vaccines are contraindicated in immunosuppressed patients (see Contraindications).
Prior or concurrent use of other medicinal products with similar myelosuppressant action as etoposide may be expected to have additive or synergetic effects (see Precautions).
Cross resistance between anthracyclines and etoposide has been reported in preclinical experiments.
Paediatric population: Interaction studies have only been performed in adults.
Caution For Usage
Special precautions for disposal and other handling: Procedures for proper handling and disposal of anti-cancer medicinal products should be followed.
Care must be taken whenever handling cytostatic products. Always take steps to prevent exposure. As with other potentially toxic compounds, caution should be exercised in handling and preparing etoposide solutions. Skin reactions associated with accidental exposure to etoposide may occur. The use of gloves is recommended. If etoposide should contact the skin or mucosa, immediately wash the skin with soap and water and flush the mucosa with water.
Etoposide solutions must be prepared under aseptic conditions.
Preparation of etoposide 100 mg powder for solution for infusion: Before use the content of each vial must be reconstituted with 5 ml or 10 ml of: water for injections or, 5% glucose solution or, 0.9 % sodium chloride solution.
This will yield a reconstituted stock solution containing 20 mg/ml or 10 mg/ml etoposide.
After reconstitution, the solution can be administered without further dilution or it can be further diluted with 5% glucose solution or 0.9% sodium chloride solution to obtain concentrations as low as 0.1 mg/ml etoposide.
The products administered by parenteral route must be visually examined to check for any particulates or discoloration prior to administration. If any discolouration or particulate matter is observed, the reconstituted solution must be discarded.
Etoposide is for single use only. Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
[Etoposide 1000 mg powder for solution for infusion]: Preparation of etoposide 1000 mg powder for solution for infusion: Etoposide 1000 mg is intended to be handled by pharmaceutical staff in central hospital units for the preparation of cytostatics. All steps of preparation must be carried out under Laminar Air Flow conditions. Solutions should be prepared under aseptic conditions. The stopper of the vial should be pierced only once and a sterile transfusion set or any other auxiliary device should be used for withdrawal for the solution. If spikes are used they should be equipped with particle filters or other measures should be taken (e.g. inline-filters) to ensure that only particle free solutions are administered.
The content of each injection vial of etoposide 1000 mg has to be diluted in 100 ml of: water for injections or, 5% glucose solution or, 0.9% sodium chloride solution.
This will yield a reconstituted stock solution containing 10 mg/ml etoposide.
The resulting stock solution may be administered without further dilution or can be further diluted with 5% glucose solution or 0.9% sodium chloride solution to a final concentration of 0.1 mg/ml etoposide.
The stock solution should be withdrawn under aseptic conditions according to the physician's prescription and transferred to the infusion bottles and/or syringes for the individual patients. Exact measuring must be ensured for withdrawal. The stock solution should be used as soon as possible (see Shelf-life under Storage).
Products administered by parenteral route must be visually examined to check for any particulates or discolouration prior to administration. If any discolouration or particulate matter is observed, the reconstituted solution must be discarded.
Any unused medicinal product or waste material should be disposed of in accordance with local requirements.
Incompatibilities: In the absence of compatibility studies, this medicinal product must not be mixed with other medicinal products.
Etoposide must not be diluted with buffered solutions with a pH value 8, as it precipitates in this milieu.
Storage
Do not store above 25°C.
Shelf-life: 3 years.
Residuals to be discarded.
The ready-to-use solution for infusion is stable for 24 hours when prepared properly (see Special precautions for disposal and other handling under Cautions for Usage).
ATC Classification
L01CB01 - etoposide ; Belongs to the class of plant alkaloids and other natural products, podophyllotoxin derivatives. Used in the treatment of cancer.
Presentation/Packing
Conc for soln for infusion (vial) 20 mg/mL x 5 mL x 1's
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