Vindesine, a semisynthetic vinca alkaloid is derived from vinblastine.

It is used in the treatment of the following conditions:

• Resistant childhood acute lymphoblastic leukemia

• Advanced breast cancer unresponsive to appropriate endocrine surgery and/or hormonal therapy (if indicated)

• Treatment of blast crisis of chronic myeloid leukemia

• Treatment of unresponsive malignant melanoma

Off Label Usage of Vindesine in Adults: ​​​​​​​

• Non-Hodgkin lymphoma (diffuse large B-cell);

• T-cell leukemia/ lymphoma

Vindesine Dose in Adults

Dose in the treatment of advanced Breast cancer:

• Adults:
  • The initial dose is 3 mg/m²
  • If no toxicity and granulocyte count is acceptable ( sustained granulocyte counts  less than 2,500/mm should be avoided ) then increase the dose in 0.5 mg/m increments at weekly intervals
  • Do not increase the dose if granulocyte count less than 1,500/mm³, platelet count less than 100,000/mm³, or if acute abdominal pain is present.
  • The usual dosage range is 3 to 4 mg/m²
  • The maximum dose/week is 4 mg/m².

Dose in the treatment of chronic myeloid leukemia (blast crisis):

• Adults:
  • Initially, 3 mg/m² is given
  • If no toxicity and granulocyte count is acceptable ( sustained granulocyte counts  less than 2,500/mm³ should be avoided ) then increase dose in 0.5 mg/m² increments at weekly intervals
  • Do not increase dose if granulocyte count  less than 1,500/mm³, platelet count  less than 100,000/mm³, or if acute abdominal pain is present.
  • Usual dosage range is 3 to 4 mg/m²
  • maximum dose/week is 4 mg/m².

Dosage in the treatment of unresponsive malignant Melanoma:

• Adults:
  • Initially, 3 mg/m² intravenously is given
  • If no toxicity and granulocyte count is acceptable ( sustained granulocyte counts  less than 2,500/mm should be avoided ) then increase the dose in 0.5 mg/m² increments at weekly intervals
  • Do not increase dose if granulocyte count  less than 1,500/mm³, platelet count  less than 100,000/mm³, or if acute abdominal pain is present.
  • Usual dosage range is 3 to 4 mg/m²
  • The maximum dose/week is 4 mg/m².

Off label dosage in the treatment of diffuse large B-cell Non-Hodgkin lymphoma:

• Adults ≤59 years:
  • 2 mg/m² intravenous given on days 1 and 5 every 14 days (along with doxorubicin, cyclophosphamide, bleomycin, prednisone, and rituximab [R-ACVBP regimen]) for 4 cycles (with growth factor support)
  • It is followed by sequential consolidation therapy.
• Adults <61 years:
  • 2 mg/m² intravenous given on days 1 and 5 every 14 days (along with doxorubicin, cyclophosphamide, bleomycin, prednisone [ACVBP regimen]) for 3 cycles (with growth factor support)
  • It is followed by sequential consolidation therapy.

Off label dosage in the treatment of T-cell leukemia and lymphoma :

• Adults:
  • 4 mg/m² intravenous is given on day 15 (as part of the VCAP-AMP-VECP multi-agent chemotherapy regimen).

Vindesine Dose in Childrens

Dosage in the treatment of resistant Acute lymphoblastic leukemia:

• Children:
  • Initially 4 mg/m² intravenously is given
  • If no toxicity and granulocyte count is acceptable (avoid sustained granulocyte counts <2,500/mm³), then dose can be increased in 0.5 mg/m² increments at weekly intervals
  • Do not increase dose if granulocyte count <1,500/mm³ , platelet count <100,000/mm³ or if acute abdominal pain occurs
  • Usual dosage range is 4 to 5 mg/m .

Dosing adjustment for toxicity:​​​​​​​

• Children:
  • Gastrointestinal toxicity (acute abdominal pain):
    • Withhold dose temporarily.
    • After treatment is restarted, do not increase the dose above the dose where acute abdominal pain occurred.
  • Neurotoxicity:
    • It may require dose reduction or temporary discontinuation.
  • Pulmonary toxicity (progressive dyspnea requiring chronic therapy):
    • Discontinue (do not restart).

Pregnancy risk Category: D

• Studies on animal reproduction suggest that there are teratogenic factors.
• Effective contraception should be used to prevent pregnancy in women with childbearing capacity and men who have female partners.

Use of vindesine during breastfeeding

• It is not recommended to use during breast-feeding.

Vindesine dose in renal disease:

• There are no dosage adjustments given in the manufacturer’s labeling. 

Vindesine dose in Liver disease:

• Dosage reductions may be required for significant hepatic or biliary impairment

Side effects of Vindesine (Frequency not defined).

• Central Nervous System:
  • Chills
  • Convulsions
  • Decreased Deep Tendon Reflex
  • Depression
  • Headache
  • Malaise
  • Neurotoxicity
  • Peripheral Neuritis
  • Tingling Sensation Of Hands Or Feet
• Dermatologic:
  • Alopecia
  • Cellulitis
  • Localized Vesiculation Mouth
  • Maculopapular Rash
• Gastrointestinal:
  • Abdominal Pain
  • Anorexia
  • Constipation
  • Diarrhea
  • Dyspepsia
  • Dysphagia
  • Intestinal Obstruction
  • Nausea
  • Paralytic Ileus
  • Perforated Duodenal Ulcer
  • Stomatitis
  • Vomiting
• Hematologic & Oncologic:
  • Granulocytopenia
  • Mild Anemia
  • Thrombocythemia
  • Thrombocytopenia
• Local:
  • Injection Site Reaction
• Neuromuscular & Skeletal:
  • Foot-Drop
  • Jaw Pain
  • Musculoskeletal Pain
  • Weakness
• Respiratory:
  • Bronchospasm
  • Dyspnea
• Miscellaneous:
  • Fever

Contraindication to Vindesine Include:

• Hypersensitivity to vindesine sodium sulfate, or any part thereof
• Intrathecal administration can be fatal
• Charcot-Marie-Tooth Syndrome: Demyelinating variant
• Severe Granulocytopenia (1500/mm3 or severe thrombocytopenia
• Severe bacterial infections

Warnings and precautions

• Suppression of bone marrow
  • Granulocytopenia refers to the dose-limiting toxicity
  • The nadir generally occurs between 3 and 5 days after administration
  • The recovery process is fast and completes in 7-10 days.
  • If granulocytes count less than 1,000/mm, it is important to monitor for infection.
  • If you give your blood test more often than once weekly, you could get thrombocytopenia.
  • Even though platelets are not affected or may increase when vindesine administered weekly, thrombocytopenia can be more common if platelets are already low prior to treatment.
  • Mild anemia is possible (rare).
• Extravasation
  • Vindesine can be used as a vesicant
  • Before and during infusion, ensure proper needle and catheter placement.
  • Avoid excessive extravasation. It can cause severe irritation.
  • Extravasation can be stopped immediately. You should also apply moderate heat to the affected area and local injections of hyaluronidase.
  • To complete administration, you can use another vein.
• Gastrointestinal effects
  • There may be nausea, constipation and vomiting.
  • If you are experiencing severe abdominal pain, monitor for paralytic ileus.
  • To prevent obstipation, patients should be prescribed a prophylactic bowel regime.
• Neurotoxicity:
  • Paresthesias, jaw pains, loss of deep tendon reflexes and foot drop can all be caused by neurotoxicity.
  • You may need to reduce the dose.
  • Patients with neuromuscular diseases should be cautious; neurotoxicity can occur.
  • The neurotoxicity of vindesine is less severe/progressive that other vinca alkaloids.
• Respiratory effects
  • Vinca alkaloids have been shown to cause severe bronchospasm and acute shortness of breath.
  • It can be caused by mitomycin in combination.
  • Patients with preexisting pulmonary toxicities may experience severe symptoms.
  • The time it takes for the symptoms to appear can vary from minutes to hours following vinca administration to up to two weeks after mitomycin.
  • Progressive dyspnea is possible.
  • If pulmonary dysfunction is present, stop permanently taking vindesine
• Hepatic impairment
  • Patients with hepatic impairment should be cautious.
  • For severe biliary or liver impairment, a reduction in dosage may be required.

Vindesine (United States: Not available): Drug Interaction

Monitor:

• CBC with differential count
• liver function tests
• monitor infusion site
• monitor for infection
• Monitor neurotoxicity or pulmonary toxicity.

How to administer Vindesine?

It is only administered via the intravenous route.

• It is fatal if given by other routes.
• The World Health Organization (WHO) strongly advises dispensing vinca alkaloids in a minibag (NOT in a syringe).
• Vindesine should NOT be given to the patient at the same time with any medications intended for central nervous system administration.
• Administer as a rapid IV push over 1 - 3 minutes into a free flowing IV line.
• Vesicant & ensure proper needle or catheter placement before and during infusion
• Avoid extravasation.

Extravasation management:

• If extravasation occurs, discontinue infusion immediately and disconnect
• Leave cannula & needle in place
• Gently aspirate extravasated solution  & do not flush the line
• Start hyaluronidase antidote & remove needle/cannula
• Apply dry warm compresses for 20 minutes 4 times a day for 1 - 2 days
• Elevate extremity.
• The remaining portion of the vindesine dose should be given through a separate vein.

Hyaluronidase:

• If needle/cannula still in place then administer 1 to 6 mL hyaluronidase (150 units/mL) into the existing IV line
• The usual dose given is 1 mL hyaluronidase for each 1 mL of the extravasated drug.
• If needle/cannula was removed then inject 1 to 6 mL (150 units/mL) subcutaneously in a clockwise manner using 1 mL for each 1 mL of drug extravasated.
• Alternative is administer 1 mL (150 units/mL) as 5 separate 0.2 mL injections (using a 25-gauge needle) subcutaneously into the extravasation site.

Mechanism of action of Vindesine:

• It is semisynthetic vinca, derived from vinblastine.
• It works by binding and stabilizing tubulin, disrupting the formation the mitotic spindle. This arrests the cell cycle at the metaphase.

Metabolism: Hepatic route

Excretion: By Feces and urine 

International Brands of Vindesine:

• Ae De Xin
• Eldisin
• Eldisine
• Enison
• Fildesin
• Gesidine
• Xi Ai Ke

Vindesine Brands in Pakistan:

Vindesine is not available in Pakistan