VP-Gen

VP-Gen Uses, Dosage, Side Effects, Food Interaction and all others data.

VP-Gen is a derivative of podophyllotoxin that inhibits DNA synthesis resulting in the arrest of the cell cycle. At low doses, it inhibits cells from entering cell cycle and at high doses, cells entering mitosis are lysed.

VP-Gen is an antineoplastic agent and an epipodophyllotoxin (a semisynthetic derivative of the podophyllotoxins). It inhibits DNA topoisomerase II, thereby ultimately inhibiting DNA synthesis. VP-Gen is cell cycle dependent and phase specific, affecting mainly the S and G2 phases. Two different dose-dependent responses are seen. At high concentrations (10 µg/mL or more), lysis of cells entering mitosis is observed. At low concentrations (0.3 to 10 µg/mL), cells are inhibited from entering prophase. It does not interfere with microtubular assembly. The predominant macromolecular effect of etoposide appears to be the induction of DNA strand breaks by an interaction with DNA-topoisomerase II or the formation of free radicals.

Trade Name VP-Gen
Availability Prescription only
Generic Etoposide
Etoposide Other Names Etoposide, Etoposido, Etoposidum, trans-Etoposide
Related Drugs methotrexate, Keytruda, carboplatin, pembrolizumab, fluorouracil, doxorubicin, cisplatin, paclitaxel, cyclophosphamide, Avastin
Type
Formula C29H32O13
Weight Average: 588.5566
Monoisotopic: 588.18429111
Protein binding

97% protein bound.

Groups Approved
Therapeutic Class Cytotoxic Chemotherapy
Manufacturer
Available Country Argentina, Peru
Last Updated: September 19, 2023 at 7:00 am
VP-Gen
VP-Gen

Uses

Small Cell Lung Cancer: VP-Gen Capsules in combination with other approved chemotherapeutic agents as first line treatment in patients with small cell lung cancer.

VP-Gen is also used for Testicular cancer, Small cell lung cancer.

VP-Gen is also used to associated treatment for these conditions: Acute Lymphoblastic Leukaemias (ALL), Acute Myeloid Leukemia (AML), Advanced Hodgkin's Lymphoma, Ewing's Sarcoma, Gestational Trophoblastic Disease, Merkel cell cancer, Multiple Myeloma (MM), Neuroblastomas, Neuroendocrine Tumours, Non-Hodgkin's Lymphoma (NHL), Non-Small Cell Lung Carcinoma (NSCLC), Ovarian Cancer, Prostate Cancer, Retinoblastoma, Sarcoma, Osteogenic, Small Cell Lung Cancer (SCLC), Wilms' tumor, Locally advanced Thymoma, Metastatic Thymic Cancer, Refractory Sarcoma, Refractory Testicular cancer

How VP-Gen works

VP-Gen inhibits DNA topoisomerase II, thereby inhibiting DNA re-ligation. This causes critical errors in DNA synthesis at the premitotic stage of cell division and can lead to apoptosis of the cancer cell. VP-Gen is cell cycle dependent and phase specific, affecting mainly the S and G2 phases of cell division. Inhibition of the topoisomerase II alpha isoform results in the anti-tumour activity of etoposide. The drug is also capable of inhibiting the beta isoform but inhibition of this target is not associated with the anti-tumour activity. It is instead associated with the carcinogenic effect.

Dosage

VP-Gen dosage

Intravenous (Adult)-

Small cell lung cancer:35 mg/m2/day for 4 days to 50 mg/m2/day for 5 days. May repeat course at 3-4 wkly intervals after recovery from any toxicity. Inj must be diluted with 5% dextrose or normal saline to give a final concentration of 0.2-0.4 mg/ml and injected over 30-60 minutes. When given via oral capsules: the recommended dose is twice the IV dose rounded to the nearest 50 mg.

Testicular cancer:For combination therapy: 50-100 mg/m2/day from days 1-5, or 100 mg/m2 on days 1, 3 and 5. May repeat course at 3-4 wkly intervals after recovery from any toxicity. Inj must be diluted with 5% dextrose or normal saline to give a final concentration of 0.2-0.4 mg/ml and injected over 30-60 minutes.

Oral (Adult)-

Small cell lung cancer:Twice the IV dose, rounded to the nearest 50 mg.

Side Effects

Leukopenia, Nausea and Vomiting, Thrombocytopenia, Alopecia, Anorexia, Diarrhea, Leukopenia, Anemia, Pancytopenia, Stomatitis, Hepatic toxicity, Type 1 hypersensitivity, Orthostatic hypotension, Peripheral neuropathy.

Malaise,Shivering,Asthenia,Fever,Mucous membrane inflammation, Hyperuricemia, Local soft tissue toxicity has been reported following extravasation;

Toxicity

Side effects include alopecia, constipation, diarrhea, nausea and vomiting and secondary malignancies (leukemia).

Precaution

Skin reactions may occur with accidental exposure; renal or hepatic disease. Periodic CBCs should be done before, during and after therapy. Increased risk of etoposide-toxicity in patients with low serum albumin. Acrylic material has been shown to crack and leak when used with undiluted etoposide inj.

Interaction

Synergism with other cytotoxic drugs. Caution when admin with drugs that inhibit phosphatase activity. Cyclosporin A may reduce the clearance of etoposide.

Food Interaction

  • Avoid grapefruit products. Grapefruit inhibits CYP3A4 metabolism, which may increase the serum concentration of etoposide.
  • Exercise caution with St. John's Wort. This herb induces CYP3A4 metabolism, which may reduce serum levels of etoposide.

Volume of Distribution

The disposition of etoposide is a biphasic process with a distribution half-life of 1.5 hours. It does not cross into cerebrospinal fluid well. Volume of distribution, steady state = 18 - 29 L.

Elimination Route

Absorbed well, time to peak plasma concentration is 1-1.5 hrs. Mean bioavailability is 50% (range of 25% - 75%). Cmax and AUC values for orally administered etoposide capsules display intra- and inter-subject variability. There is no evidence of first-pass effect for etoposide.

Half Life

4-11 hours

Clearance

  • Total body clearance = 33 - 48 mL/min [IV administration, adults]
  • Mean renal clearance = 7 - 10 mL/min/m^2

Elimination Route

VP-Gen is cleared by both renal and nonrenal processes, i.e., metabolism and biliary excretion. Glucuronide and/or sulfate conjugates of etoposide are also excreted in human urine. 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. 56% of the dose was in the urine, 45% of which was excreted as etoposide.

Pregnancy & Breastfeeding use

Pregnancy category D. There is positive evidence of human fetal risk based on adverse reaction data from investigational or marketing experience or studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks.

Lactation: not known if excreted in breast milk, discontinue drug or do not nurse

Contraindication

Hypersensitivity, pregnancy, lactation.

Special Warning

Renal impairment: CrCI: 15-50 ml/min- 75% of the recommended dose.

Innovators Monograph

You find simplified version here VP-Gen

VP-Gen contains Etoposide see full prescribing information from innovator VP-Gen Monograph, VP-Gen MSDS, VP-Gen FDA label

*** Taking medicines without doctor's advice can cause long-term problems.
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