Vinblastine

Vinblastine Sulfate Injection (vinblastine sulfate) is indicated in the palliative treatment of the following neoplastic diseases: Frequently Responsive Malignancies • Generalized Hodgkin's disease (Stages III and IV, Ann Arbor modification of Rye) • Lymphocytic lymphoma (modular and diffuse, poorly and well differentiated) • Histiocytic lymphoma • Mycosis fungoides (advanced stages) • Advanced carcinoma of the testis • Kaposi's Sarcoma • Letterer-Siwe disease (histiocytosis-X) Less Frequently Responsive Malignancies • Choriocarcinoma resistant to other neoplastic drugs • Cancer of the breast (unresponsive to endocrine surgery and hormonal therapy) The simultaneous use of several cancer chemotherapy drugs is common practice.

Generally, drugs with different dose-limiting clinical toxicities and different mechanisms of action are selected in order to obtain an increase in therapeutic response without added toxicity. Rarely is it possible to obtain equally as good a response with single antineoplastic treatment.

Therefore, vinblastine is often part of polychemotherapy because, at the recommended doses, it does not cause significant suppression of the bone marrow or neuropathy. This approach to multiple treatment has been used in the chemotherapy of Hodgkin's disease.

Hodgkin's disease Vinblastine has been found to be one of the most effective single antineoplastic agents for the treatment of Hodgkin's disease. Successful treatment of advanced Hodgkin's disease has been accomplished by the use of various multiple-drug regimens that have included vinblastine.

Patients who have relapsed following treatment with the MOPP-regimen (mechlorethamine hydrochloride [nitrogen mustard], vincristine sulfate, prednisone and procarbazine) have often responded to combination drug therapy that included vinblastine.

An alternative therapy that has been used in previously untreated patients with advanced Hodgkin's disease employs cyclophosphamide in place of nitrogen mustard and vinblastine instead of vincristine. Advanced testicular germinal-cell cancers such as embryonal carcinoma, teratocarcinoma, and choriocarcinoma have been shown to be sensitive to vinblastine alone but a more satisfactory clinical response may be obtained by the concomitant administration of vinblastine with other anti-tumor drugs.

The efficacy of bleomycin has been found to be enhanced if vinblastine is given 6 - 8 hours prior to bleomycin. This procedure appears to result in more cells being arrested during metaphase, the stage of cell division in which bleomycin is active.

1 Pediatrics Pediatrics: Based on the data submitted and reviewed by Health Canada, the safety and efficacy of Vinblastine Sulfate Injection in pediatric patients has been established. Therefore, Health Canada has authorized an indication for pediatric use (see 4 DOSAGE AND ADMINISTRATION).

4 Geriatrics).

). 4 Geriatrics). 2 CONTRAINDICATIONS The use of vinblastine is contraindicated in patients with leukopenia. Vinblastine should not be administered to patients with bacterial infections. Such infections must be brought under control by the use of antibiotic or antiseptic therapy prior to the initiation of vinblastine treatment.

Pregnancy Although no abnormalities of the human fetus have been associated with the use of vinblastine, information on its use during pregnancy is limited. Animal studies suggest that vinblastine may be teratogenic. 1 Pregnant Women).

Vinblastine Sulfate Injection is contraindicated in patients who are hypersensitive to this drug or to any ingredient in the formulation, including any non-medicinal ingredient, or component of the container. For a complete listing, see

Table 2. Adverse Drug Reaction Table System Organ Class Adverse Drug Reactions Blood and lymphatic system disorders Neutropenia Endocrine disorders Inappropriate anti-diuretic hormone secretion Nervous system disorders Cerebrovascular accidenta, neurotoxicity Ear and labyrinth disorders VIIIth cranial nerve injuryb, ototoxicity Cardiac disorders Myocardial infarctiona a in combination chemotherapy with vinblastine, bleomycin and cisplatin.

b Manifestations include partial or total deafness, which may be temporary or permanent, and difficulties with balance, including dizziness, nystagmus and vertigo. Leukopenia Bone-marrow depression, especially leukopenia, is the most common adverse effect with vinblastine and tends to be dose-limiting.

Before administering the drug, patients should be advised of the possibility of adverse reactions. Maximum depression occurs 4 - 10 days after administration, with recovery in one to three weeks. Except for epilation and leukopenia the adverse reactions seen with vinblastine usually do not persist for more than 24 hours.

Gastrointestinal Nausea, vomiting, constipation, vesiculation of the mouth, ileus, diarrhea, anorexia, abdominal pain, rectal bleeding, pharyngitis, hemorrhagic enterocolitis and bleeding from a dormant peptic ulcer may occur. Product Monograph PrVINBLASTINE SULFATE INJECTION (vinblastine sulfate) Page 11 of 23 Neurologic Neurologic effects can involve the autonomic nervous system and include malaise, headache, depression, psychoses, paresthesia, neuromyopathy, loss of deep tendon reflexes, peripheral neuritis, constipation, numbness and convulsions.

Miscellaneous Epilation, malaise, weakness, dizziness, pain at the site of the tumor, and vesiculation of the skin may occur. Epilation is frequently not complete and in some instances hair re-growth will occur even though therapy continues.

Cellulitis and phlebitis may result if extravasation occurs during intravenous injection. If the extravasation is excessive, sloughing may occur.

The use of vinblastine is contraindicated in patients with leukopenia. Vinblastine should not be administered to patients with bacterial infections. Such infections must be brought under control by the use of antibiotic or antiseptic therapy prior to the initiation of vinblastine treatment.

Pregnancy Although no abnormalities of the human fetus have been associated with the use of vinblastine, information on its use during pregnancy is limited. Animal studies suggest that vinblastine may be teratogenic. 1 Pregnant Women).

Vinblastine Sulfate Injection is contraindicated in patients who are hypersensitive to this drug or to any ingredient in the formulation, including any non-medicinal ingredient, or component of the container. For a complete listing, see 6 DOSAGE FORMS, STRENGTHS, COMPOSITION AND PACKAGING.

Vinblastine sulfate is a cytotoxic drug that arrests cell growth at the metaphase. Its actions are more pronounced on the rapidly dividing cell than on the normal cell. It appears to act, like vincristine, by binding to the microtubular proteins of the mitotic spindle, preventing polymerisation.

Information available at present suggests that vinblastine sulfate may be useful, either alone or in combination with other oncolytic drugs, for the treatment of: Hodgkin’s disease; non-Hodgkin’s lymphoma; carcinoma of the breast; methotrexate-resistant choriocarcinoma; renal cell carcinoma; testicular teratoma and seminoma; histiocytosis X.

Other neoplasms occasionally show a marked response to vinblastine sulfate, but less frequently than the more susceptible conditions listed above.

Posology The recommended dose for adults, the elderly and children is 6 mg/m2, usually administered no more frequently than once every seven days. 2 mg/kg administered on each of two consecutive days every three weeks. To minimise the possibility of extravascular spillage, it is suggested that the syringe and needle be rinsed with venous blood before withdrawal.

The dose should not be diluted in large volumes of diluent (ie, 100 to 250 ml) or given intravenously for prolonged periods (ranging from 30 to 60 minutes or more), since this frequently results in irritation of the vein and increases the chance of extravasation.

Because of the enhanced possibility of thrombosis, it is considered inadvisable to inject a solution of vinblastine sulfate into an extremity in which the circulation is impaired, or potentially impaired, by such conditions as compressing or invading neoplasm, phlebitis or varicosity.

Patients with hepatic impairment As vinblastine is excreted principally by the liver, toxicity may be increased when there is hepatic insufficiency and it may be necessary to reduce initial doses in the presence of significantly impaired hepatic or biliary function.

A reduction of 50% in the dose is recommended for patients having a direct serum bilirubin value above 3 mg/100 ml. Patients with renal impairment Since metabolism and excretion are primarily hepatic, no modification is recommended for patients with impaired renal function.

Vinblastine should not be given intramuscularly, subcutaneously or intrathecally. Method of administration The solution may be injected either directly into the vein or into the injection site of a running intravenous infusion. Injection of vinblastine sulfate may be completed in about one minute.

FOR INTRAVENOUS USE ONLY. 4) In case of mistaken administration by intrathecal route, see section

The use of small amounts of vinblastine daily for long periods is not advisable, even though the resulting total dosage may be similar to the recommended dosage. Little or no therapeutic advantage has been demonstrated when such regimens have been used and side-effects are increased.

The incidence of side effects with vinblastine sulfate appears to be dose related and most do not persist longer than 24 hours. Neurological effects are uncommon but can occur and may last longer than 24 hours.

The frequency grouping is defined using the following convention:

Not known (cannot be estimated from the available data). Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness. Infections and infestations Not known Pharyngitis Neoplasms benign, malignant and unspecified (incl.

cysts and polys) Not known Tumour pain Blood and lymphatic system disorders Not known Neutropenia, Leucopeniaa, Thrombocytopenia, Anaemia Endocrine disorders Not known Inappropriate anti-diuretic hormone secretionb Metabolism and nutrition disorders Not known Anorexia Psychiatric disorders: Not known Depression Nervous system disorders Not known Cerebrovascular accidentc Convulsions, Numbness, Neuropathy peripheral, Loss of deep tendon reflexes, Paraesthesia Headache, Dizziness Ear and labyrinth disorders Not known VIIIth nerve injuryd Cardiac disorders Not known Myocardial infarctionc Vascular disorders Not known Hypertension, Raynaud’s phenomenone Respiratory, thoracic and mediastinal disorders Not known Dyspnoeaf, Acute respiratory distressf Gastrointestinal disorders Not known Haemorrhagic enterocolitis, Rectal bleeding, Peptic ulcer haemorrhage, Ileus, Nauseag, Vomitingg, Constipation, Oral mucosal blistering, Diarrhoea, Abdominal pain, Stomatitis Skin and subcutaneous tissue disorders: Not known Blister, Alopeciah Musculosketetal and connective tissue disorders Not known Myalgia, Bone pain, Jaw pain Reproductive system and breast disorders Not known Aspermia General disorders and administration site conditions Not known Injection site phlebitis, Injection site cellulitis (and in extreme cases skin exfoliation), Extravasation, Malaise, Asthenia a Leucopoenia is the most common side effect and dose limiting factor.

b Syndrome of inappropriate ADH secretion has been reported with higher than recommended doses. c In combination chemotherapy with vinblastine sulfate, bleomycin and cisplatin. d Treatment with vinca alkaloids has resulted rarely in both vestibular and auditory damage to the eighth cranial nerve.

Manifestations include partial or total deafness, which may be temporary or permanent, and difficulties with balance including dizziness, nystagmus, and vertigo. Particular caution is warranted when vinblastine sulfate is used in combination with other agents known to be ototoxic, such as the platinum-containing oncolytics.

e Raynaud’s phenomenon has occurred when patients are being treated with vinblastine in combination with bleomycin and cisplatin for testicular cancer. 5). g antiemetics may be used to control nausea and vomiting. h usually not total and in some cases the hair regrows during maintenance therapy).

Reporting of suspected adverse reactions Reporting suspected adverse reactions after authorisation of the medicinal product is important. It allows continued monitoring of the benefit/risk balance of the medicinal product. uk/yellowcard or search for MHRA Yellow Card in the Google Play or Apple App Store.

1. For intravenous use only. 4). Vinblastine sulfate is contraindicated in patients who are leucopenic. Vinblastine sulfate should not be used in the presence of bacterial infection. Such infections should be brought under control with antiseptics or antibiotics before the initiation of therapy with vinblastine sulfate.