The incidence of adverse events listed below was determined according to the following gradation: very often (> 1/10); often (> 1/100, ≤ 1/10); infrequently (> 1/1000, ≤ 1/100); rarely (> 1/10000, ≤ 1/1000); rarely (≤ 1/10000), including individual messages; the frequency is unknown - according to the available data, it is not possible to determine the frequency of occurrence.
Combined therapy with oxaliplatin and fluorouracil / calcium folinate
Laboratory and instrumental data:
ABOUTFrequently:
- PIncreased activity of "liver" transaminases, alkaline phosphatase, hyperbilirubinemia, increased lactate dehydrogenase activity, weight gain.
Often:
- Diprekreatininemia, weight loss.
Infectious and parasitic diseases:
Often:
- Infections.
Often:
- Infections of the upper respiratory tract, neutropenic sepsis (including fatal outcomes).
Infrequently:
- Sepsis (including fatal outcomes).
Violations of the blood and lymphatic system:
Often:
- Anemia, neutropenia, thrombocytopenia, leukopenia, lymphopenia.
The incidence of these side effects increases with Eloxatin® (85 mg / m2 every 2 weeks) in combination with fluorouracil +/- calcium folinate in comparison with monotherapy with Eloxatin ® 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 <8 g / dL) or severe thrombocytopenia (platelet count <50000 / μL) occurred with the same frequency (<5% of patients,when the Eloxatin preparation was used in the form of monotherapy or in combination with fluorouracil).
Severe neutropenia (the number of neutrophils <1000 / μL) occurred more frequently with Eloxatin® plus fluorouracil compared with Eloxatin® monotherapy (40% compared with <3% of patients).
Often:
- Febrile neutropenia (including grade 3-4).
Rarely:
- Immunoallergic hemolytic anemia and thrombocytopenia.
Disorders from the digestive system:
Often:
- Nausea, vomiting, diarrhea, constipation.
With severe diarrhea and / or vomiting may be associated development dehydration, hypokalemia, metabolic acidosis, paralytic intestinal obstruction, obstruction of the thin intestines, function disorders kidney, especially when using the combination of Eloxatin® and fluorouracil.
- Stomatitis or mucositis (inflammation of the mucous membranes).
- Stomach ache.
Often:
- Dyspepsia.
- Gastroesophageal reflux disease.
- Gastrointestinal bleeding.
- Bleeding from the rectum.
Rarely:
- Colitis, including pseudomembranous colitis, caused by Clostridium difficile.
- Pancreatitis.
Disturbances from the liver and bile ducts:
Rarely:
- Hepatic Syndrome sinusoidal obstruction, also known as veno-occlusive disease of the liver or pathological manifestations, associated with this disease liver, including peliogenic hepatitis, nodal regenerative hyperplasia, perisinusoidal fibrosis, clinical manifestations which can be portal hypertension and / or increase activity "hepatic" transaminase in the serum.
Impaired nervous system:
Often:
- Acute neurosensory manifestations.
These symptoms usually occur in end of a 2-hour infusion of the Eloxatin preparation or for several hours after drug administration and independently decrease in for the next few hours or days and often reappear in subsequent cycles. They can arise or increase with exposure to low temperatures or cold items. Usually they expressed in the appearance of transitory paresthesia, dysesthesia and hypoesthesia. Acute laryngopharyngeal syndrome dysesthesia occurs in 1-2% patients and is characterized by subjective sensations dysphagia or dyspnea / sensations choking without any objective respiratory disorders (absence cyanosis or hypoxia), or laryngospasm or bronchospasm (without stridor or wheezing).
Other, sometimes encountered symptoms, in particular, violations function of the cranial nerves as associated with the above undesirable phenomena, and isolated: 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.
- Dysaestia or paresthesia of the extremities and peripheral sensory neuropathy.
The limiting toxicity of Eloxatin® is neurological toxicity. It manifests itself in the form of peripheral sensory neuropathy, characterized by peripheral dysesthesia and / or paresthesia with or without the development of convulsive muscle contractions, 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, as well as their duration, are indications for correcting the dosing regimen or even canceling the treatment (see the section "Dosage and administration, recommendations for correcting the oxaliplatin dosage regimen"). 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.
- Dysgeusia (a violation of taste sensations).
- Headache.
Often:
- Dizziness.
- Meningism.
Rarely:
- Dysarthria.
- The disappearance of deep tendon reflexes.
- Symptom of Lermitt.
- Syndrome of posterior reversible leukoencephalopathy (see section "Special instructions").
Disorders of the psyche:
Often:
- Depression.
- Insomnia.
Infrequently:
- Nervousness.
Disturbances from musculoskeletal and connective tissue:
Often:
- Back pain.
In the case of such an undesirable reaction, the patient should be examined to exclude hemolysis, as there were rare reports of its development.
Often:
- Arthralgia, pain in the bones.
Disturbances from the respiratory system, chest and mediastinal organs:
Often:
- Shortness of breath.
- Cough.
Often:
- Hiccup.
- Pulmonary embolism.
Rarely:
- Acute interstitial defeat of the lungs, sometimes with fatal; pulmonary fibrosis (see section "Special instructions").
Vascular disorders:
Often:
- Nose bleed.
Often:
- "Tides".
Deep vein thrombosis.
- Thromboembolism.
- Increased blood pressure pressure.
Disorders from the kidneys and urinary tract:
Often:
- Hematuria.
- Dizuria.
Rarely:
- Acute tubular necrosis, acute interstitial nephritis, acute renal failure.
Disturbances from the skin and subcutaneous tissues:
Often:
- Defeat of the skin.
Often:
- Alopecia (less than 5% patients with monotherapy).
- Erythematous rash.
- Palmar-plantar erythrodysesthesia.
- Increased sweating.
- Changes from the nails.
Disorders from the side of the organ of vision:
Rarely:
- Transient reduction in severity vision, narrowing of the fields of vision, neuritis optic nerve.
- Transient loss of vision, reversible upon termination treatment.
Hearing disorders and labyrinthine disorders:
Infrequently:
- Ototoxicity.
Rarely:
- Deafness.
Immune system disorders:
Often:
- Allergic reactions, such as a skin rash (in particular, urticaria), conjunctivitis, rhinitis.
Often:
- Anaphylactic reactions, including bronchospasm, angioedema, decrease blood pressure, sensation pain in the chest and anaphylactic shock.
General disorders and disorders at the site of administration:
Often:
- Increased fatigue.
- Fever, chills (shivering) or because of the development of infections (with febrile neutropenia or without her), or, possibly, as a result of immunological mechanisms.
- Asthenia.
- Reactions at the site of administration.
It was reported about the development of reactions together administration, including pain, flushing, edema and thrombosis. Extravasation (getting the infusion solution with the drug into the veins surrounding the vein) can also lead to local pain and inflammation that can be severe and lead to complications, including necrosis, especially when the Eloxatin® drug is injected through the peripheral vein.
Disorders from the metabolism and nutrition:
Often:
- Anorexia, hyperglycemia, hypernatremia.
Post-marketing experience
Infectious and parasitic diseases: frequency unknown - septic shock (including fatal outcomes).
Violations of the blood and lymphatic system: frequency unknown - hemolytic-uremic syndrome.
Impaired nervous system: frequency is unknown - convulsions.
Disturbances from the respiratory system, chest and mediastinal organs: frequency is unknown - laryngospasm.