Vinorelsin

Vinorelsin Uses, Dosage, Side Effects, Food Interaction and all others data.

Vinorelsin, a semisynthetic vinblastine derivative, binds to tubulin and inhibits microtubule formation. This disrupts the formation of the mitotic spindle thereby arresting the cell at metaphase.

Vinorelsin is a semi-synthetic vinca-alkaloid with a wide spectrum of anti-tumor activity. The vinca-alkaloids are considered spindle poisons. They work by interfering with the polymerization of tubulin, a protein responsible for building the microtubule system which appears during cell division in proliferating cancer cells .

Trade Name Vinorelsin
Availability Prescription only
Generic Vinorelbine
Vinorelbine Other Names 5'-Noranhydrovinblastine, Vinorelbin, Vinorelbina, Vinorelbine, Vinorelbinum
Related Drugs Opdivo, methotrexate, Keytruda, pembrolizumab, cisplatin, Tagrisso, Avastin
Type
Formula C45H54N4O8
Weight Average: 778.947
Monoisotopic: 778.394164715
Protein binding

80-90%

Groups Approved, Investigational
Therapeutic Class Cytotoxic Chemotherapy
Manufacturer
Available Country Bosnia & Herzegowina, Croatia (Hrvatska), Serbia, Vietnam
Last Updated: September 19, 2023 at 7:00 am
Vinorelsin
Vinorelsin

Uses

Vinorelsin is used for:

  • In combination with cisplatin for first-line treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC)
  • As a single agent, for the treatment of patients with metastatic NSCLC

Vinorelsin is also used to associated treatment for these conditions: Advanced Non Small Cell Lung Cancer, Esophageal Cancers, Locally Advanced Non-Small Cell Lung Cancer, Metastatic Breast Cancer, Recurrent Cervical Cancer, Soft Tissue Sarcoma (STS), Recurrent, IV-B Cervical cancer

How Vinorelsin works

Vinca alkaloids are structurally similar compounds composed of two multi-ringed units, vindoline, and catharanthine. Vinorelsin tartrate is a vinca alkaloid in which the catharanthine component is the target of structural modification , .

This structural modification contributes to unique pharmacologic properties.The antitumor activity of vinorelbine tartrate is believed to be owed to the inhibition of mitosis at metaphase via its interaction with tubulin .

Vinorelsin is a mitotic spindle poison that interferes with chromosomal segregation during mitosis, also known as cell division. It pauses cells at the G2/M phases, when present at concentrations close to the half maximal inhibitory concentration (IC50). Microtubules, which are derived from polymers of tubulin, are the main target of vinorelbine.

The chemical modification used to produce vinorelbine allows for the opening of the eight-member catharanthine ring with the formation of both a covalent and reversible bond with tubulin .

The relative contribution of different microtubule-associated proteins in the production of tubulin vary between neural tissue and proliferating cells and this has important functional implications. The ability of vinorelbine to bind specifically to mitotic rather than other microtubules has been shown and may suggest that neurotoxicity is less likely to be a problem than with the molecular mechanism of action .

As with other anti-microtubule agents, vinorelbine is known to contribute apoptosis in malignant cells. The exact mechanisms by which this process occurs are complex and many details are yet to be elucidated. The disarray of the microtubule structure has a number of effects, including the induction of tumor suppressor gene p53 and activation/inactivation of a number of protein kinases involved in essential signaling pathways, including p21 WAF1/CIP1 and Ras/Raf, PKC/PKA. These molecular changes lead to phosphorylation and consequently inactivation of the apoptosis inhibitor Bcl2. This, in turn, results in a decrease in the formation of heterodimers between Bcl2 and the pro-apoptotic gene BAX, stimulating the sequence of cell apoptosis .

Vinorelsin tartrate also possibly interferes with amino acid, cyclic AMP and glutathione metabolism, calmodulin-dependent Ca++-transport ATPase activity, cellular respiration, and nucleic acid and lipid biosynthesis .

Dosage

Vinorelsin dosage

Intravenous (Adult):

Cervical cancer:30 mg/m2/dose days 1 and 8 of a 21-day treatment cycle.

Breast cancer, Ovarian cancer :25 mg/m2/dose every 7 days.

Non-small cell lung cancer:

  • As single agent: 30 mg/m2wkly as infusion over 20-30 minutes (after diluting in 125 ml normal saline or glucose 5%) or as slow bolus over 5-10 minutes (after diluting in 20-50 ml normal saline or glucose 5%). Delay subsequent doses if neutrophil count is <2000 cells/mm3until recovery.
  • As combination therapy with cisplatin: 25-30 mg/m2every 7 days.

Oral(Adult):

Non-small cell lung cancer:60 mg/m2once wkly for 3 wk, may increase subsequently to 80 mg/m2once wkly. If neutrophil count is < 500 cells/mm3or between 500-1000 cells/mm3on 2 separate occasions, keep dose at 60 mg/m2for next 3 doses.

Side Effects

Neurotoxicity, peripheral paraesthesia, loss of deep tendon reflexes, abdominal pain, severe constipation, diarrhoea, alopecia, severe local irritation. Dose limiting granulocytopenia, leukopenia and anaemia. Intestinal obstruction, paralytic ileus, nausea, vomitinh, increased in LFT, chest pain, fatigue. Local pain and thrombophlebitis with repeated Inj.

Toxicity

Due to the wide array of adverse effects of this drug, the toxicity of is categorized into organ systems .

Hematologic: Granulocytopenia was the primary dose-limiting toxicity with vinorelbine tartrate therapy; it is generally reversible and not cumulative. In one study, granulocytopenia resulted in hospitalizations for fever and/or sepsis in 8% of NSCLC and 9% of breast cancer patients . Infectious (septic) deaths occurred in about 1% of patients. Grade 3 or 4 anemia occurred in about 1% of lung cancer and approximately 14% of breast cancer patients. Blood transfusions were administered to 18% of patients who received vinorelbine tartrate therapy. The incidence of Grade 3 and 4 thrombocytopenia was found to be less than 1% .

Neurologic: Mild to moderate peripheral neuropathy may occur. Symptoms of paresthesia and hypesthesia are reported as the most commonly reported neurologic toxicities of this drug. The loss of deep tendon reflexes (DTR) occurs in less than 5% of patients, according to one study. The development of severe peripheral neuropathy is rare .

Dermatologic: Alopecia has been reported in only about 12% of patients and is usually reported as mild. Vinorelsin tartrate is a moderate vesicant, leading to injection site reactions. Symptoms include erythema, pain at the injection site and vein discoloration occurred in about 1/3 of all patients. Chemical phlebitis along the vein, near the site of injection, has been reported .

Respiratory: Shortness of breath was reported in 3% of NSCLC and 9% of breast cancer patients, and was severe in 2% of each patient population. Interstitial pulmonary changes have been documented in a few patients .

Gastrointestinal: Mild or moderate nausea symptoms occurred in 32% of NSCLC and 47% of breast cancer patients treated with vinorelbine tartrate. Severe nausea was occurred infrequently (1% and 3% in NSCLC and breast cancer patients, respectively). Prophylactic administration of anti-emetics was not routine in patients treated with single-agent vinorelbine tartrate. Constipation occurred in about 28% of NSCLC and 38% of breast cancer patients. The paralytic ileus incidence of less than 2% of patients. Vomiting, diarrhea, anorexia and stomatitis were found to be mild or moderate and occurred in less than 20% of study patients .

Hepatic: Transient elevations of liver enzymes were reported without clinical symptoms. Cardiovascular: Chest pain was reported in 5% of NSCLC and 8% of breast cancer patients. Most reports of chest pain were in patients who had either a history of cardiovascular disease or tumor within the chest. There have been rare reports of myocardial infarction; however, these have not been shown definitely attributable to vinorelbine tartrate .

Other: Muscle weakness (asthenia) occurred in about 25% of patients with NSCLC and 41% of patients with breast cancer. It was usually mild or moderate but showed a linear increase with cumulative doses .

Several other toxicities reported in approximately 5% of patients include jaw pain, myalgia, arthralgia, headache, dysphagia, and skin rash. Hemorrhagic cystitis (bladder inflammation with blood in urine) and the syndrome of inappropriate ADH secretion were both reported in less than 1% of patients. The treatment of these entities are mainly symptomatic .

The carcinogenic potential of Vinorelsin has not been adequately studied. Vinorelsin has been demonstrated to affect chromosome number and likely the chromosome structure in vivo (polyploidy in bone marrow cells from Chinese hamsters and a positive micronucleus test in mice were observed) .

Precaution

Hepatic impairment. Compromised bone marrow reserve due to prior irradiation or chemotherapy; recovering marrow function from the effects of previous chemotherapy. Prior radiation therapy; past history or pre-existing neuropathy. CBC with differentials to be monitored prior to admin of subsequent doses. Delay subsequent doses, if neutrophil count < 2000 cells/mm3. Each admin to be followed by at least 250 ml of normal saline to flush the vein. Avoid extravasation. If extravasation occurs, stop infusion immediately, and flush the vein with normal saline solution; admin the remaining solution in another vein. Do not father a child during and up to six mth after treatment and females of childbearing potential to use effective method of contraception during treatment and three mth thereafter. When admin orally, capsules must be swallowed whole with water and not chewed or sucked.

Interaction

Increased risk of granulocytopenia with cisplatin. Increased risk of neurotoxicity with paclitaxel, itraconazole, ketoconazole. Increased radiosensitising effects with prior or concomitant radiation therapy. Increased pulmonary toxicity with mitomycin. Increased myelotoxicity with zidovudine. Earlier onset and/or an increased severity of side effects with CYP3A inhibitors. Possible increase in vincristine levels with aprepitant. Possible infection with live vaccines.

Food Interaction

  • Exercise caution with grapefruit products. Grapefruit inhibits CYP3A4 metabolism and may increase the serum levels of vinorelbine.
  • Exercise caution with St. John's Wort. This herb induces CYP3A4 metabolism and may reduce the serum levels of vinorelbine.

Volume of Distribution

The volume of distribution is large, indicating extensive extravascular distribution .

The steady-state volume of distribution values range from 25.4 to 40.1 L/kg, according to one study .

Widely distributed, with highest amounts found in elimination organs such as liver and kidneys, minimal in heart and brain .

Elimination Route

Vinorelsin is rapidly absorbed with peak serum concentration reached within 2 hours .

Vinorelsin is highly bound to platelets and lymphocytes and is also bound to alpha 1-acid glycoprotein, albumin, and lipoproteins .

Half Life

The terminal phase half-life averaged 27.7 to 43.6 hours; the mean plasma clearances ranged from 0.97 to 1.26 L/hr/kg .

Clearance

The plasma clearance of vinorelbine is high, approaching the same as hepatic blood flow in humans, and its volume of distribution is large, indicating extensive extravascular distribution. In comparison to vinblastine or vincristine .

The clearance was found to be in the range of 0.29-1./26 L/ per kg in 4 clinical trials of patients receiving 30 mg/m2 of vinorelbine .

Elimination Route

Vinorelsin undergoes substantial hepatic elimination in humans, with large amounts recovered in feces after intravenous administration to humans .

Urinary excretion of unchanged drug accounts for less than 20% of an intravenous dose, with fecal elimination accounting for an additional 30% to 60% .

After intravenous administration of radioactive vinorelbine, approximately 18% and 46% of administered radioactivity was recovered in urine and feces, respectively .

Pregnancy & Breastfeeding use

Pregnancy Category D. There is positive evidence of human foetal risk, but the benefits from use in pregnant women may be acceptable despite the risk (e.g., if the drug is needed in a life-threatening situation or for a serious disease for which safer drugs cannot be used or are ineffective).

Contraindication

Hypersensitivity to vinorelbine or other vinca alkaloids; severe current or recent infection (within last 2 wk); neutropenia; thrombocytopenia; severe hepatic impairment. Intrathecal admin. Do not give concomitantly with radiotherapy if liver is in treatment field. Pregnancy, lactation.

Special Warning

Hepatic Impairment:Intravenous:

  • Cervical cancer: Dose adjustments may be needed.
  • Breast cancer, Ovarian cancer: Dose adjustments may be needed.
  • Non-small cell lung cancer: Massive liver metastases(>75% of liver volume replaced by the tumour): Decrease dose by 1/3. Bilirubin 2.1-3 mg/100 ml: Reduce IV dose by 50%. Bilirubin >3 mg/100 ml: Reduce IV dose by 75%.

Oral:

  • Massive liver metastases(>75% of liver volume replaced by the tumour): Decrease dose by 1/3. Bilirubin 2.1-3 mg/100 ml: Reduce IV dose by 50%. Bilirubin >3 mg/100 ml: Reduce IV dose by 75%.

Storage Condition

Intravenous: Store at 2-8°C. Protect from light. Oral: Store at 2-8°C.

Innovators Monograph

You find simplified version here Vinorelsin

Vinorelsin contains Vinorelbine see full prescribing information from innovator Vinorelsin Monograph, Vinorelsin MSDS, Vinorelsin FDA label

FAQ

What is Vinorelsin used for?

Vinorelsin is used alone and in combination with other medications to treat non-small cell lung cancer  that has spread to nearby tissues or to other parts of the body.Vinorelsin is in a class of medications called vinca alkaloids.

How safe Vinorelsin is?

Data from these trials indicate that Vinorelsin is safe and well tolerated in the outpatient population.

What are the common side effects of Vinorelsin ?

Common side effects may include:

  • nausea, vomiting, constipation;
  • weakness;
  • numbness or tingling in your hands or feet;
  • low blood cell counts;
  • abnormal liver function tests; or.
  • pain, redness, bruising, or irritation around the IV needle.

How Vinorelsin is given?

Vinorelsin is given through a vein by intravenous injection or infusion.

Is Vinorelsin safe during pregnancy?

This drug can cause fetal harm when administered to a pregnant woman.

Is Vinorelsin safe during breastfeeding?

You'll be advised not to breastfeed during treatment and for at least three weeks after your last dose of Vinorelsin. This is because there is a chance that your baby may absorb the drug through your breast milk, which can cause harm.

Can I drink alcohol with Vinorelsin ?

The drinking of alcohol (in small amounts) does not appear to affect the safety or usefulness of Vinorelsin .

How often is Vinorelsin given?

Recommended dosage of Vinorelsin is 30 mg/m2 administered as an intravenous injection or infusion over 6 to 10 minutes once a week in combination with cisplatin 120 mg/m2 on Days 1 and 29, then every 6 weeks.

Is Vinorelsin a chemo drug?

Vinorelsin is a chemotherapy drug used to treat non-small cell lung cancer and breast cancer that has come back after treatment.

Do I lose hair on Vinorelsin?

Vinorelsin may cause some mild, temporary hair thinning. Very rarely, it can cause complete hair loss.

What does Vinorelsin do to cells?

Vinorelsin works by stopping the cancer cells from separating into 2 new cells. So, it stops the growth of the cancer.

Does Vinorelsin cause nausea?

Nausea, vomiting, fatigue, constipation, diarrhea, dizziness, muscle aches, joint pain, or irritation at the injection site may occurs.

Is there any food or drink I need to avoid when taking Vinorelsin?

Vinorelsin capsules should be swallowed whole with a glass of water and with some food. Avoid taking them with a hot drink, as the capsules may dissolve in the mouth.

Does Vinorelsin cause constipation?

Vinorelsin can cause bowel problems, most often constipation. Drinking plenty of water and eating a high-fibre diet can help make constipation less severe.

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