DBL Vincristine Sulfate Adverse Reactions

Prior to the use of vincristine, patients and or parents/guardians should be advised of the possibility of untoward symptoms.
In general, adverse effects are reversible and are related to dosage. The most common adverse effect is hair loss; the most troublesome adverse effects are neuromuscular in origin. When single, weekly doses of the drug are employed, the adverse effects of leucopenia, neuritic pain, and constipation occur but are of short duration (i.e. less than 7 to 10 days). When the dosage is reduced, these effects may lessen or disappear. The severity of such effects seems to increase when the calculated amount of vincristine is given in divided doses. Other adverse effects such as hair loss, sensory loss, paraesthesia, difficulty in walking, slapping gait, loss of deep-tendon reflexes, and muscle wasting, may persist for at least as long as therapy is continued. Generalised sensorimotor dysfunction may become progressively more severe with continued treatment. Although most such symptoms usually disappear by about the sixth week after discontinuance of treatment, some neuromuscular difficulties may persist for prolonged periods in some patients. Regrowth of hair may occur while maintenance therapy continues.
The following adverse effects have been reported: Immune system disorders: Rare cases of allergic-type reactions, such as anaphylaxis, rash and oedema, that are temporarily related to vincristine therapy have been reported in patients receiving vincristine as a part of multidrug chemotherapy regimens.
Gastrointestinal disorders: Autonomic toxicity such as constipation and paralytic ileus are not uncommon and are frequently associated with abdominal cramps. Stool softeners, mild laxatives and enemas may be helpful. A routine prophylactic regimen of laxative and enemas is usually recommended for patients receiving vincristine.
Constipation may take the form of upper colon impaction, and on physical examination, the rectum may be empty. Colicky abdominal pain coupled with an empty rectum may mislead the physician. A flat film of the abdomen is useful in demonstrating this condition.
Paralytic ileus (which mimics the 'surgical abdomen') may occur, particularly in young children and in the elderly. The ileus will reverse itself with temporary discontinuance of vincristine and with symptomatic care.
Nausea, vomiting, diarrhoea, anorexia, stomatitis, oral ulceration, intestinal necrosis and/or perforation, abdominal cramps and abdominal distension occur occasionally.
Hepatobiliary disorders: Venoocclusive liver disease has been reported, especially in children.
Renal and urinary disorders: Hyperuricaemia may occur in some patients receiving vincristine, especially those with non-Hodgkin's lymphomas or leukaemia. In some patients uric acid nephropathy may result. These effects may be minimised by adequate hydration, alkalinisation of the urine and/or administration of allopurinol (see Interactions). Allopurinol may be preferred to minimise hyperuricaemia, because of the risk of uric acid nephropathy with uricosuric antigout agents.
Polyuria, oliguria, nocturia, dysuria, and urinary retention due to bladder atony have occurred. Other drugs known to have caused urinary retention (particularly in the elderly) should, if possible, be discontinued for the first few days following administration of vincristine sulfate. Increased urinary retention is especially likely to occur in elderly male patients with varying degrees of obstructive uropathy. Urinary incontinence has also been reported.
Cardiac and vascular disorders: Hypertension and hypotension have occurred. Chemotherapy combinations that have included vincristine sulfate, when given to patients previously treated with mediastinal radiation, have been associated with coronary artery disease and myocardial infarction. Causality has not been established. Thromboembolism has been reported when bleomycin has been administered with vinca alkaloids and other agents such as cisplatin or etoposide; such combinations have also been implicated in producing Raynaud's syndrome.
Nervous system disorders: Neurotoxicity is the most common dose-limiting side effect of vincristine. Frequently, there is a sequence to the development of neuromuscular side effects. Initially, only sensory impairment and paraesthesiae may be encountered. With continued treatment, neuritic pain and later, motor difficulties may occur. There have been no reports made of any agent that can reverse the neuromuscular manifestations that may accompany therapy with vincristine. Vincristine may exacerbate the signs and symptoms in patients with pre-existing neurological disorders. Consideration should be given to discontinuing treatment if neuromuscular effects continue to be a problem.
Loss of deep-tendon reflexes, foot drop, wrist drop, ataxia, and paralysis have been reported with continued administration. Cranial nerve manifestations, including isolated paresis and/or paralysis of muscles controlled by cranial motor nerves, may occur in the absence of motor impairment elsewhere; extra-ocular and laryngeal muscles are those most commonly involved. Numbness of the fingers and toes, atrophy, cramps, slapping gait, and difficulty in walking or inability to walk, may occur. Jaw pain, pharyngeal pain, parotid gland pain, bone pain, back pain, limb pain, testicular pain and myalgias have been reported; pain in these areas may be severe. Convulsions, frequently with hypertension, have been reported in a few patients receiving vincristine sulfate. Several instances of convulsions followed by coma have been reported in children.
Sympathetic neuropathy may occur. Peripheral neuritis and neuralgia occur frequently.
Peroneal nerve palsy (manifesting as foot drop and slapping gait), areflexia, nerve injury have been reported.
Treatment with vinca alkaloids has resulted very rarely (<0.01%) in vestibular and auditory damage to the eighth cranial nerve. Manifestations include partial or total deafness, which may be permanent or temporary, and difficulties with balance including dizziness, nystagmus and vertigo. Vincristine should only be used concurrently with other potentially ototoxic drugs, such as the platinum-containing antineoplastic agents, with extreme caution.
Patients with existing neurological disorders such as poliomyelitis or Charcot-Marie-Tooth Syndrome may be at increased risk of neurotoxicity.
Psychiatric disorders: Depression, agitation, insomnia, hallucinations and altered state of consciousness have been reported.
Eye disorders: Transient cortical blindness and optic atrophy with blindness have been reported.
Respiratory, thoracic and mediastinal disorders: Oropharyngeal pain, acute respiratory distress syndrome and bronchospasm can occur (see Precautions).
Endocrine, metabolism and nutrition disorders: Hypersecretion of antidiuretic hormone (SIADH) has occurred rarely in patients receiving vincristine therapy. In these patients, hyponatraemia associated with increased urinary sodium excretion occurs without evidence of renal or adrenal disease, hypotension, dehydration, azotaemia or clinical oedema. With fluid deprivation, improvement occurs in the hyponatraemia and in the renal loss of sodium. Decreased appetite is also very common.
Blood and lymphatic system disorders: Vincristine sulfate does not appear to have any constant or significant effect on platelets or red blood cells. Serious bone-marrow depression is usually not a major dose-limiting event. However, anaemia, leucopenia, and thrombocytopenia have been reported. Thrombocytopenia, if present when therapy with vincristine is begun, may actually improve before the appearance of bone marrow remission. Granulocytopenia can also occur.
Skin and subcutaneous tissue disorders: Alopecia is reported to occur in about 20% to 70% of patients who receive vincristine. It is reversible when vincristine is discontinued. Rash has also been reported, as have photosensitivity reactions.
Vincristine may cause a severe local reaction, resulting in pain and cellulitis, on extravasation (see Precautions).
Other: Fever and headache have occurred. Also other side effects include defective sweating, myoclonic jerks, abnormal Vasalva response, impotence and diminished libido. Weight loss has been reported at high doses.