0

Zuvitop Inj

 Etoposide  Inj –  100MG

  • Etoposide Injection is indicated in the management of the following neoplasms.
  • Small cell lung cancer,  malignant lymphomas
  • Acute leukemia’s… Testicular tumors.
  • Bladder Cancer. Trophoblastic  diseases
  • Etoposide Injection are indicated in the management of the following neoplasms.
  • Small cell lung cancer.  Malignant lymphomas.

Zuvitop-100 (etoposide Injection, IP) is a semisynthetic derivative of podophyllotoxin used in the treatment of certain neoplastic diseases. It is 4′-demethylepipodophyllotoxin 9-[4,6-0-(R)- ethylidence – B-D- glucopyranoside]. It is very soluble in methanol and chloroform, slightly soluble in ethanol, and sparingly soluble in water and ether. It is made more miscible with water by means of organic solvents. It has a molecular weight of 588.58 and a molecular formula of C29 H32 O13.

The Structural formula is :

Zuvitop-100

Each ml contains:

Etoposide            IP            20 mg

Citric Acid            IP            2 mg

Polysorbate 80  IP            80 mg

Polyethylene glycol 300IP            650 mg

Benzoyl alcoholIP            30 mg

Ethyl alcohol       IP            30.5% v/v

  • 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 of 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. Etoposide does not accumulate in the plasma following daily  administration of 100 mg/m2 for 4 or 5 days.
  • The mean volumes of  distribution at steady state fall in the range of 18 to 29 liters or 7 to 17  L/m2. Etoposide enters the CSF poorly. Although it is detectable in CSF and  intracerebral tumors, the concentrations are lower than in extracerebral tumors  and in plasma. Etoposide concentrations are higher in normal lung than in lung  metastases and are similar in primary tumors and normal tissues of the  myometrium. In vitro, etoposide is highly protein bound (97%) to human plasma  proteins. An inverse relationship between plasma albumin levels and etoposide  renal clearance is found in children. In a study determining the effect of  other therapeutic agents on the in vitro binding of carbon-14 labeled etoposide  to human serum proteins, only phenylbutazone, sodium salicylate, and aspirin  displaced protein-bound etoposide at concentrations achieved in vivo.
  • Etoposide binding  ratio correlates directly with serum albumin in patients with cancer and in  normal volunteers. The unbound fraction of etoposide significantly correlated  with bilirubin in a population of cancer patients. Data have suggested a  significant Inverse correlation between serum albumin concentration and free  fraction of etoposide.
  • After intravenous  administration of 14C-etoposide (100 to 124 mg/m2), mean recovery of  radioactivity in the urine was 56% of the dose at 120 hours, 45% of which was  excreted as etoposide: fecal recovery of radioactivity was 44% of the dose at  120 hours.
  • 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, i.e., metabolism  and biliary excretion. The effect of renal disease on plasma etoposide  clearance is not known.
  • Biliary excretion  of unchanged drug and/or metabolites is an important route of etoposide  elimination as fecal recovery of radioactivity is 44% of the intravenous dose.  The hydroxy acid metabolite [4’-demethylepipodophyllic  acid-9-(4,6-O-(R)-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. Only 8% or less of an  intravenous dose is excreted in the urine as radiolabeled metabolites of  14C-etoposide. In addition, O-demethylation of the dimethoxyphenol ring occurs  through the CYP450 3A4 isoenzyme pathway to produce the corresponding catechol.
  • After intravenous  infusion, the Cmax and AUC values exhibit marked intra- and inter-subject  variability.
  • There is no  evidence of a first-pass effect for etoposide. For example, no correlation  exists between the absolute oral bioavailability of etoposide capsules and  nonrenal clearance. No evidence exists for any other differences in etoposide  metabolism and excretion after administration of oral capsules as compared to  intravenous infusion.
  • In adults, the  total body clearance of etoposide is correlated with creatinine clearance,  serum albumin concentration, and nonrenal clearance. Patients with impaired  renal function receiving etoposide have exhibited reduced total body clearance,  increased AUC and a lower volume of distribution at steady state. Use of  cisplatin therapy is associated with reduced total body clearance. In children,  elevated serum SGPT levels are associated with reduced drug total body  clearance. Prior use of cisplatin may also result in a decrease of etoposide  total body clearance in children.
  • Although some minor  differences in pharmacokinetic parameters between age and gender have been  observed, these differences were not considered clinically significant.
  • Etoposide Injection is  indicated in the management of the following neoplasms.
  • Small cell lung cancer,  malignant lymphomas
  • Acute leukemia’s… Testicular  tumors.
  • Bladder Cancer. Trophoblastic  diseases
  • Etoposide Injection are  indicated in the management of the following neoplasms.
  • Small cell lung cancer.  Malignant lymphomas.

Hematologic toxicity: Myelosuppression is dose-related and dose-limiting with granulocyte nadirs occurring 7 to 14 days after drug administration and platelet nadirs occurring 9 to 16 days after drug administration. Bone marrow recovery is usually complete by day 20 and no cumulative toxicity has been reported.

Gastrointestinal Toxicity: 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.

Hypotension: 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, slower administration rate should be used.

Allergic reactions: 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.

Alopecia: Reversible alopecia, sometimes progressing to total baldness was observed in upto 66% of patients.

Other toxicities: The following adverse reactions have been infrequently reported: rash, fever, pigmentation, pruritus, abdominal pain, constipation, dysphagia, transient cortical blindness and a single report of radiation recall dermatitis.

OVER DOSAGE:

No proven antidotes have been established for Etoposide overdosage.

CONTRAINDICATIONS:

Etoposide is contraindicated in patients who have demonstrated a previous Hypersensitivity to it.