The frequency of adverse reactions below, is described according to the following gradation: very often (> 10%), frequent (> 1%, and ≤ 10%), infrequently (> 0.1% and ≤ 1%), rarely (> 0.01% and ≤ 0,1%), very rarely (≤0.01%), including individual reports; the frequency is unknown - according to the available data, it is not possible to determine the frequency of occurrence.
Violations from the blood and lymphatic system:
very often - anemia, leukopenia, neutropenia, thrombocytopenia, lymphopenia.
The incidence of these side effects increases with treatment with oxaliplatin (85 mg / m2 every 2 weeks) in combination with fluorouracil ± calcium folinate in comparison with monotherapy with preparations of oxaliplatin in a dose of 130 mg / m2 every 3 weeks, for example, the incidence of anemia (80% compared to 60%), the incidence of neutropenia (70% compared to 15%), the rate of thrombocytopenia (80% compared to 40%).
Severe anemia (hemoglobin <80 g / L), or severe thrombocytopenia (platelets <50x109/ L) occurred with similar frequency (<5% of patients when used in formulations of oxaliplatin alone or in combination with fluorouracil).
Severe neutropenia (number of neutrophils <1x109/ l) appeared more frequently with oxaliplatin preparations in combination with fluorouracil compared with oxaliplatin monotherapy (40% compared with 15% of patients);
often - febrile neutropenia (including grade 3-4), sepsis against neutropenia;
rarely - hemolytic anemia, immune thrombocytopenia.
Disorders from the gastrointestinal tract:
very often - nausea, vomiting, diarrhea, stomatitis or mucositis (inflammation of the mucous membranes), abdominal pain, constipation, loss of appetite;
Severe diarrhea and / or vomiting can be associated with the development of dehydration, hypokalemia, metabolic acidosis, intestinal obstruction, renal dysfunction, especially with a combination of platinum and fluorouracil;
often - dyspepsia, gastroesophageal reflux, hiccough, gastrointestinal bleeding;
infrequently - intestinal obstruction, incl. paralytic;
rarely - colitis, including cases of pseudomembranous colitis (caused by Clostridium difficile), pancreatitis.
Disorders from the liver and bile ducts:
very often - increased activity of alkaline phosphatase, lactate dehydrogenase, "hepatic" transaminases, increased bilirubin concentration;
very rarely - a syndrome of hepatic sinusoidal obstruction, also known as vein-occlusive liver disease or pathological manifestations associated with this liver disease, including peliosis hepatitis, nodal regenerative hyperplasia, perisinusoidal fibrosis, whose clinical manifestations may be portal hypertension or increased activity " hepatic "transaminases, alkaline phosphatase in the blood serum;
Disorders of the psyche:
often - depression, insomnia.
Impaired nervous system:
very often - acute neurosensory manifestations, peripheral sensory neuropathy, sensitivity disorders, dysesthesia, headache, paresthesia of the extremities, dysgeusia (a violation of taste sensations).
Acute neurosensory manifestations - these symptoms usually occur at the end of a 2-hour infusion of oxaliplatin preparations or within a few hours after the administration of the drugs and self-decrease for the next few hours or days and often reappear in subsequent cycles. They can arise or intensify when exposed to low temperatures or cold objects.Usually they are expressed in the appearance of transient paresthesia, dysesthesia and hypesthesia.
Acute syndrome of laryngeal pharyngeal dysesthesia occurs in 1-2% of patients and is characterized by subjective sensations of dysphagia or dyspnea / sensation of suffocation without any objective signs of respiratory disorders (absence of cyanosis or hypoxia) or laryngospasm or bronchospasm (absence of stridor or wheezing).
Other, sometimes encountered symptoms, in particular, disorders of the cranial nerves, or associated with the above undesirable phenomena or occur in isolation: ptosis; diplopia (double vision); aphonia, dysphonia, hoarseness, sometimes described as paralysis of the vocal cords; a violation of the sensitivity of the tongue or dysarthria, sometimes described as aphasia; neuralgia of the trigeminal nerve, facial pain, eye pain, decreased visual acuity, narrowing of the visual fields. In addition, the following symptoms were observed: spasm of masticatory muscles, muscle spasms, involuntary muscle contractions, muscle twitching, myoclonus; impaired coordination, gait disturbance, ataxia, imbalance; feeling of pressure / feeling of pressure / discomfort / pain in the pharynx or chest.
As a rule, these symptoms quickly stop as without the use of drug therapy, and with the introduction of antihistamines and bronchodilators. Increasing the infusion time in subsequent cycles of oxaliplatin therapy can reduce the incidence of such symptoms.
The limiting toxicity of oxaliplatin is neurological toxicity. It manifests itself in the form of peripheral sensory neuropathy characterized by peripheral dysaesthesia and / or paresthesia with or without the development of convulsive muscle contractions, which is often provoked by cold (85-95% of patients).
The time of maintenance of these symptoms, which usually decrease between treatment cycles, increases with the number of treatment cycles that have been performed. The occurrence of pain or functional disorders and their duration are indications for correcting the dosing regimen or even canceling the treatment (see section "Dosage and administration, recommendations for correcting the dosage regimen of oxaliplatin"). These functional disorders, including difficulties in performing precise movements, are consequences of sensory disturbances.The risk of functional impairment for a cumulative dose of approximately 800 mg / m2 (for example, 10 cycles) is <15%. In most cases, neurologic manifestations and symptoms decrease after discontinuation of treatment. In most cases, these neurological symptoms are weakened or they completely stop. However, in 3% of patients 3 years after the end of treatment there were either stable localized paresthesia of moderate intensity (2.3%) or paresthesia, affecting functional activity (0.5%);
rarely - dysarthria, disappearance of deep tendon reflexes, a symptom of Lermitt, a syndrome of reversible posterior leukoencephalopathy.
The symptom of Lermitt is a sudden feeling of electric shock, spreading downwards along the spine and into both legs. It occurs when the head is tilted, other neck movements or coughing. Possible variants of Lermitt's symptom are tingling with neck movements or pain during neck movements, the spreading of unpleasant sensations in both hands and the appearance of unpleasant sensations during movements in the lumbar spine.
Signs and symptoms of reversible parieto-occipital leukoencephalopathy can be headache, mental disability, seizures,visual impairment (from vague images to blindness), combined or not with increasing blood pressure. The diagnosis of reversible posterior leukoencephalopathy is confirmed by magnetic resonance imaging or computed tomography of the brain.
Disturbances from the musculoskeletal and connective tissue:
very often - back pain;
In case of occurrence of such undesirable reaction, the patient should be examined to exclude hemolysis, since there were rare reports of its development;
often - arthralgia, pain in the bones.
Disturbances from the respiratory system, chest and mediastinal organs:
very often - cough, shortness of breath;
often - rhinitis, infections of the upper respiratory tract;
rarely - acute interstitial lung involvement, sometimes fatal, pulmonary fibrosis.
Heart Disease:
often - pain behind the sternum. Vascular disorders:
very often - nosebleeds;
often - bleeding, hot flushes, deep vein thrombosis, pulmonary artery thromboembolism, increased blood pressure.
Disorders from the kidneys and urinary tract:
often - increasing the concentration of creatinine, hematuria, dysuria, frequent urination;
very rarely - acute tubular necrosis, acute interstitial nephritis, acute renal failure.
Disturbances from the skin and subcutaneous tissues:
very often - alopecia (less than 5% of patients with monotherapy), skin rashes;
often - peeling of the skin of the palms and feet, erythematous rashes, rashes, excessive sweating, changes from the nails.
Disorders from the side of the organ of vision:
often - conjunctivitis, visual impairment;
rarely - transient reduction in visual acuity, narrowing and / or loss of visual fields, optic neuritis, transient loss of vision, reversible after discontinuation of treatment.
Hearing disorders and labyrinthine disturbances:
infrequently - ototoxicity;
rarely - hearing loss, deafness, neuritis of the auditory nerve.
Immune system disorders:
very often - allergic reactions, such as a skin rash (especially urticaria), conjunctivitis, rhinitis;
often (in combination with fluorouracil ± calcium folinate, less often with monotherapy) - anaphylactic reactions, including bronchospasm, angioedema, hypotension, chest pain and anaphylactic shock.
General disorders and disorders at the site of administration:
very often - weakness and fatigue, fever, fever, chills (or because of the development of infections (with or without febrile neutropenia) or due to a possible immune reaction), asthenia, reactions at the injection site. It was reported on the development of reactions at the site of administration, including pain, flushing, edema and thrombosis. Extravasation (getting the infusion solution with the drug into surrounding tissues) can lead to local pain and inflammation, which can be severe and lead to complications, including necrosis, especially when the drug is injected into the peripheral vein.
Disorders from the metabolism and nutrition:
very often - hypokalemia, hyponatremia, hyperglycemia, anorexia, weight gain (with adjuvant therapy);
often - dehydration, weight loss (in the treatment for metastatic cancer);
infrequently - metabolic acidosis.
Postmarketing experience with oxaliplatin preparations
Violations from the blood and lymphatic system:
frequency unknown - hemolytic-uremic syndrome.
Disturbances from the respiratory system, chest and mediastinal organs:
frequency is unknown - laryngospasm.
Impaired nervous system:
frequency unknown - convulsions, dizziness.