Adverse reactions : תופעות לוואי

4.8   Undesirable effects
In general, the side effects are reversible and dose dependent. The most important toxic effects of vincristine have been associated with the central nervous system. The most often occurring side effects are neurotoxicity and alopecia; the most troublesome side effects are neuromuscular in origin.
Side effects may be pronounced in patients with hepatic impairment due to reduced metabolism and delayed biliary excretion.
Side effects are listed by frequency, the most frequent first, using the following convention: Very common ((≥1/10); common ((≥1/100 to <1/10); uncommon
((≥1/1,000 to <1/100); rare ((≥1/10,000 to <1/1,000); very rare (<1/10,000), not known (cannot be estimated from the available data).

Within each frequency grouping, undesirable effects are presented in order of decreasing seriousness.


Neoplasms, benign and malignant and unspecified (including cysts and polyps) Treatment-related secondary malignancy.
Patients who have been treated with vincristine in combination with other cytotoxic products, of which it is known that they are carcinogenic, have developed secondary malignancies.

Blood and lymphatic system disorders
Common
      Temporary thrombocytosis.
Uncommon
Severe bone marrow depression, anaemia, leukopenia and thrombocytopenia.

Immune system disorders
Common
Acute occurrence of shortness of breath and bronchospasms, which can be severe and life- threatening. These symptoms were observed after the administration of vinca alkaloids (such as vincristine), particularly when administered concomitantly with mitomycin. The reaction can occur a few minutes to hours after the administration of a vinca alkaloid or to 2 weeks after a dose of mitomycin.
Rare
Allergic reactions, such as anaphylaxis, rash and oedema, possibly related to vincristine therapy have been observed in patients who were treated with vincristine as part of multi-drug chemotherapy regimes.

Nervous system disorders
The neurological toxicity is the most important side effect of vincristine.
Neurological toxicity is dose and age related. As a result of neurotoxicity also constipation and ileus can occur (see “Gastrointestinal system disorders”).

Common
The most frequently occurring neurotoxic side effect is peripheral neuropathy (mixed sensorimotor), which occurs in almost all patients. Often a specific order in the development of neuromuscular side effects occurs. In the beginning only sensory disturbances and paraesthesia occur. With continuation of the treatment, nerve pain (amongst other in the jaw and testicles) and further motor difficulties can occur. Loss of deep tendon reflexes, foot drop, muscle weakness, ataxia and paralysis have been reported with continuation of the treatment. Affection of the cranial nerve, amongst which isolated paresis and/or paralysis of muscles that are directed by the cranial nerves, can occur, without muscle weakness occurring anywhere else.

Paralysis of the cranial nerve and muscle weakness of the larynx can cause hoarseness and vocal cord paresis, amongst which potentially life threatening bilateral vocal cord paresis. Muscle weakness of the outer ocular muscles can cause ptosis, and optical and extra ocular neuropathy.
Transient cortical blindness has been reported. Vincristine also causes autonomic toxicity and toxicity of the central nervous system, although less frequent than peripheral neuropathy. Double vision and optic atrophy are observed.

Uncommon
Convulsions, frequently with hypertension, have been reported in a few patients receiving vincristine sulfate. A few cases of convulsions followed by coma have been reported in children. Vincristine causes autonomic toxicity and toxicity of the CNS, although this occurs less frequently than peripheral neuropathy.
Effects on the CNS e.g. altered state of awareness and mental changes like depression, agitation, sleeplessness, confusion, psychoses and hallucinations.

Not known
Leukoencephalopathy.

Ear and labyrinth disorders
Uncommon
Deafness.

Cardiac disorders
      Uncommon
Coronary artery disease, myocardial infarction.

Coronary vascular disorders and myocardial infarction have occurred in patients who were treated with vincristine containing chemotherapy combinations and who were previously treated with radiotherapy of the mediastinum.

Rare
Hypertension and hypotension.

Respiratory, thoracic and mediastinal disorders
Common
Severe bronchospasm and dyspnea have been reported with vinca alkaloids, some of which were used in combination with mitomycin C.

Gastrointestinal disorders
Common
Nausea, vomiting, constipation, abdominal pain. Constipation can occur as a result of impaction of the upper part of the intestines while the rectum is empty. Colic-like abdominal pains can then occur.

Uncommon
Reduced appetite, weight loss, anorexia, diarrhoea, paralytic ileus. Especially in young children paralytic ileus is a possibility.

Rare
Inflammation of the mucous membrane of the mouth, intestinal necrosis and/or perforation.

Very rare
Pancreatitis.
Hepatobiliary disorders
Rare
Hepatic veno-occlusive disease, particularly in children.

Skin and subcutaneous tissue disorders
Very common
Alopecia (is reversible when the administration of vincristine is discontinued).

Renal and urinary disorders
In elderly patients the therapy with drug that causes urinary retention must be interrupted in the early days after the vincristine administration.

Uncommon
Polyuria, dysuria, urinary retention as a result of bladder atony, hyperuricaemia, uric acid nephropathy.

Rare
SIADH syndrome (syndrome of inappropriate antidiuretic hormone secretion).
The syndrome may be related to the neurotoxicity of the medicinal product possibly due to a direct effect on the hypothalamus. In these patients hyponatraemia occurs, in combination with urinary sodium excretion, without indication of renal or adrenal disorders, hypotension, dehydration, azotemia or oedema. With liquid restriction the hyponatraemia and the loss of sodium through the kidneys can be improved.

      Very rare
Incontinence.

Reproductive system and breast disorders
Irreversible infertility after vincristine-containing chemotherapy is more common in males than in females.
Common
Azoospermia has been observed in men who were treated with a chemotherapy combination consisting of vincristine and prednisone with cyclophosphamide or mechlorethamine and procarbazine.
Uncommon
Amenorrhea.

General disorders and administration site conditions
Common
Injection site irritation.
Uncommon
Fever, phlebitis, pain, cellulitis and necrosis. These symptoms can occur after irritation of the vessel wall or after extravasation during the administration.
Rare
Headache.

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.
Any suspected adverse events should be reported to the Ministry of Health according to the National Regulation by using an online form: https://sideeffects.health.gov.il.