Oxaliplatin
The frequency of side effects listed below was determined according to the following gradation: very often (≥1/10), often (≥1/100, <1/10); uncommon (≥1/1000, <1/100); rare (≥1/10000, <1/1000); very rare (<1/10000), including isolated reports; frequency is unknown (it is not possible to determine the frequency of occurrence based on available data).
Combination therapy with oxaliplatin and fluorouracil/calcium folinate
Laboratory and instrumental data: very often - increased activity of liver transaminases, alkaline phosphatase, hyperbilirubinemia, increased activity of lactate dehydrogenase, increased body weight; often - hypercreatininemia, weight loss.
Infectious and parasitic diseases: very often - infections; often - upper respiratory tract infections, neutropenic sepsis (including deaths); infrequently - sepsis (including deaths).
From the blood and lymphatic system: very often - anemia, leukopenia, neutropenia, thrombocytopenia, lymphopenia. The incidence of these side effects is increased when treated with oxaliplatin (85 mg/m2 every 2 weeks) in combination with fluorouracil +/- calcium folinate compared with oxaliplatin monotherapy at a dose of 130 mg/m2 every 3 weeks, for example, the incidence of anemia (80% in compared to 60%), incidence of neutropenia (70% compared to 15%), incidence of thrombocytopenia (80% compared to 40%). Severe anemia (hemoglobin < 8 g/dL) or severe thrombocytopenia (platelet count < 50,000/μL) occurred at similar rates (< 5% of patients when oxaliplatin was used alone or in combination with fluorouracil). Severe neutropenia (neutrophil count <1000/μL) occurred at a higher rate with oxaliplatin in combination with fluorouracil compared with oxaliplatin alone (40% versus <3% of patients).
Often - febrile neutropenia (including grade 3-4); rarely - immunoallergic: hemolytic anemia and thrombocytopenia, disseminated intravascular coagulation, including deaths (see section "Special instructions").
From the digestive system: very often - nausea, vomiting, diarrhea, constipation. Severe diarrhea and/or vomiting may be associated with the development of dehydration, hypokalemia, metabolic acidosis, paralytic ileus, small intestinal obstruction, and renal dysfunction, especially when using a combination of oxaliplatin and fluorouracil. Stomatitis or mucositis (inflammation of the mucous membranes), abdominal pain; often - dyspepsia, gastroesophageal reflux disease, gastrointestinal bleeding, bleeding from the rectum; rarely - colitis, including pseudomembranous colitis caused by Clostridium difficile, pancreatitis.
Liver and biliary tract disorders: very rarely - hepatic sinusoidal obstruction syndrome, also known as veno-occlusive liver disease or pathological manifestations associated with this liver disease, including peliosis hepatitis, nodular regenerative hyperplasia, perisinusoidal fibrosis, the clinical manifestations of which may be portal hypertension and/or increased activity of “liver” transaminases in the blood serum.
From the nervous system: very often - acute neurosensory manifestations. These symptoms usually occur at the end of a 2-hour oxaliplatin infusion or within a few hours after administration of the drug and improve spontaneously over the next few hours or days and often recur in subsequent cycles. They may occur or worsen when exposed to low temperatures or cold objects. They are usually expressed in the appearance of transient paresthesia, dysesthesia and hypoesthesia. Acute laryngopharyngeal dysesthesia syndrome occurs in 1-2% of patients and is characterized by subjective sensations of dysphagia or shortness of breath/suffocation without any objective respiratory distress (no cyanosis or hypoxia), or laryngospasm or bronchospasm (no stridor or wheezing). Other sometimes occurring symptoms, in particular cranial nerve dysfunction, both associated with the above adverse events and occurring in isolation: ptosis, diplopia (double vision), aphonia, dysphonia, hoarseness, sometimes described as aphasia; trigeminal neuralgia, facial pain, eye pain, decreased visual acuity, narrowing of visual fields. In addition, the following symptoms were observed: spasm of the masticatory muscles, muscle spasms, involuntary muscle contractions, muscle twitching, myoclonus; loss of coordination, gait disturbance, ataxia, imbalance; feeling of constriction/pressure/discomfort/pain in the throat or chest. Dysesthesia or paresthesia of the limbs and peripheral sensory neuropathy. The limiting toxicity of oxaliplatin is neurological toxicity. It manifests as a 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 duration of these symptoms (the severity of which usually decreases between treatment cycles) increases with the number of treatment cycles performed. The occurrence of pain or functional impairment, as well as their duration, are indications for adjusting the dosage regimen or even discontinuing treatment. These functional impairments, including difficulty performing precise movements, are consequences of sensory impairments. The risk of functional impairment for a cumulative dose of approximately 800 mg/m2 (eg, 10 cycles) is ≤ 15%. In most cases, neurological signs and symptoms decrease after cessation of treatment. Dysgeusia (impaired sense of taste), headache. Often - dizziness, meningism; rarely - dysarthria, disappearance of deep tendon reflexes, Lhermitte's symptom, posterior reversible leukoencephalopathy syndrome (see section "Special instructions").
Mental disorders: often - depression, insomnia; infrequently - nervousness.
From the musculoskeletal and connective tissue side: very often - back pain. If such an adverse reaction occurs, the patient should be examined to exclude hemolysis, as there have been rare reports of its development. Often - arthralgia, bone pain.
From the respiratory system , chest and mediastinal organs: very often - cough, shortness of breath; often - hiccups, pulmonary embolism; rarely - acute interstitial lung damage, sometimes fatal, pulmonary fibrosis.
From the side of blood vessels: very often - nosebleeds; often - hot flashes, deep vein thrombosis, thromboembolism, increased blood pressure.
From the kidneys and urinary tract: often - hematuria, dysuria; very rarely - acute tubular necrosis, acute interstitial nephritis, acute renal failure.
From the skin and subcutaneous tissues: very often - skin damage; often - alopecia (less than 5% of patients with monotherapy), erythematous rash, palmoplantar erythrodysesthesia, increased sweating, changes in the nails.
From the organ of vision: rarely - transient decrease in visual acuity, narrowing of visual fields, optic neuritis, transient loss of vision, reversible after treatment.
On the part of the hearing organ: infrequently - ototoxicity; rarely - deafness.
From the immune system: very often - allergic reactions, such as skin rash (in particular, urticaria), conjunctivitis, rhinitis; often - anaphylactic reactions, including bronchospasm, angioedema, decreased blood pressure, chest pain and anaphylactic shock.
General disorders and administration site disorders: very common - fatigue, fever, chills (tremors) due to infections (with or without febrile neutropenia), or possibly due to immunological mechanisms, asthenia, injection site reactions.
Administration site reactions including pain, flushing, swelling and thrombosis have been reported. Extravasation (entry of the infusion solution with the drug into the tissue surrounding the vein) can also lead to local pain and inflammation, which can be severe and lead to complications, including necrosis, especially when oxaliplatin is administered through a peripheral vein.
Metabolism and nutrition: very often - anorexia, hyperglycemia, hypernatremia; often - hypocalcemia.
Post-marketing experience
Infectious and parasitic diseases: frequency unknown - septic shock (including deaths).
From the blood and lymphatic system: frequency unknown - hemolytic-uremic syndrome.
From the nervous system: frequency unknown - convulsions.
From the heart: frequency unknown - prolongation of the QT interval, which can lead to the development of severe ventricular arrhythmias, including torsade de pointes (TdP), possibly fatal.
From the respiratory system, chest and mediastinal organs: frequency unknown - laryngospasm.
From the gastrointestinal tract: frequency unknown - intestinal ischemia (including deaths), duodenal ulcer and its potential complications, such as ulcer bleeding and ulcer perforation (including deaths).
Musculoskeletal and connective tissue disorders: frequency unknown - rhabdomyolysis (including deaths).
Combination therapy of oxaliplatin with fluorouracil/calcium folinate ( FOLFOX ) and bevacizumab
The safety of the combination of oxaliplatin with fluorouracil/calcium folinate (FOLFOX) and bevacizumab as first-line therapy was assessed in 71 patients with metastatic colorectal cancer (TREE study). In addition to the adverse reactions expected from the FOLFOX regimen, adverse reactions with the combination of FOLFOX and bevacizumab included bleeding, proteinuria, impaired wound healing, gastrointestinal perforation, and hypertension.
For more detailed information regarding the safety of bevacizumab, see the appropriate prescribing information for this drug.
Oxaliplatin Medak 50 mg N1 lyophilisate for solution preparation
Latin name
OXALIPLATIN
Release form
Lyophilisate for the preparation of solution for infusion.
Compound
1 bottle contains:
Active substances: oxaliplatin 50, 100 or 150 mg.
Excipients: lactose monohydrate.
Package
The bottle contains 50, 100 or 150 mg of lyophilisate. There is 1 bottle in a cardboard package.
pharmachologic effect
Pharmacodynamics
Oxaliplatin is an antitumor drug belonging to a new class of platinum derivatives in which the platinum atom forms a complex with oxalate and 1,2-diaminocyclohexane. Oxaliplatin exhibits a wide range of cytotoxic effects. It also exhibits activity in vitro and in vivo in various cisplatin-resistant tumor models. In combination with 5-fluorouracil, a synergistic cytotoxic effect is observed.
A study of the mechanism of action of oxaliplatin confirms the hypothesis that biotransformed, aqueous derivatives of oxaliplatin, interacting with DNA by forming inter- and intrastrand bridges, suppress DNA synthesis, which leads to cytotoxicity and an antitumor effect.
Pharmacokinetics
In vivo, oxaliplatin undergoes active biotransformation and is not detected in plasma by the end of 2 hours after administration at a dose of 130 mg/m2, while 15% of the administered platinum is in the blood, and the remaining 85% is quickly distributed to tissues or excreted by the kidneys. Platinum binds to plasma albumin and is excreted in the urine within the first 48 hours.
By day 5, about 54% of the total dose is found in the urine and less than 3% in the feces. In renal failure, there is a significant decrease in oxaliplatin clearance from 17.6 l/hour to 9.95 l/hour. The effect of severe renal impairment on platinum clearance has not been studied.
Indications
— Adjuvant therapy for stage III colorectal cancer (Duke C) after radical resection of the primary tumor in combination with 5-fluorouracil and folinic acid;
- disseminated colorectal cancer (as monotherapy or combination therapy in combination with 5-fluorouracil and folinic acid).
Contraindications
- Hypersensitivity to oxaliplatin or other components of the drug;
- myelosuppression (neutrophil count less than 2000/μl and/or platelets less than 100,000/μl) before the start of the first course of treatment;
- peripheral sensory neuropathy with functional impairment before the start of the first course of treatment;
- severe renal dysfunction (creatinine clearance less than 30 ml/min);
- pregnancy;
- period of breastfeeding.
Directions for use and doses
Intravenously in the form of 2-6 hour infusions. Overhydration is not required when using oxaliplatin.
For use in adults only.
The drug should be used immediately after preparing the solution. When combined with 5-fluorouracil, the oxaliplatin infusion should precede the administration of 5-fluorouracil.
Adjuvant therapy for colorectal cancer: 85 mg/m 1 time every 2 weeks for 12 cycles (6 months).
Disseminated colorectal cancer: 85 mg/m2 once every 2 weeks as monotherapy or in combination with 5-fluorouracil.
Repeated administration of oxaliplatin is carried out only when the number of neutrophils is more than 1500/μl and platelets are more than 50,000/μl.
Recommendations for dose adjustment and administration of oxaliplatin.
In case of hematological disorders (neutrophil count < 1500/μl and/or platelets < 50,000/μl), the administration of the next course is postponed until laboratory parameters are restored.
With the development of diarrhea of grade 4 toxicity (according to the WHO scale), neutropenia of grade 3-4 (neutrophil count < 1000/μl), thrombocytopenia of grade 3-4 (platelet count < 50,000/μl), the dose of oxaliplatin for subsequent administrations should be reduced from 85 mg /m2 up to 65 mg/m2 for the treatment of disseminated colorectal cancer and up to 75 mg/m2 for adjuvant therapy in addition to the usual dose reduction of 5-fluorouracil in the case of their combined use.
For patients who develop acute laryngopharyngeal paresthesia during infusions or within several hours after 2-hour infusions, the next infusion of oxaliplatin should be administered within 6 hours.
Recommendations for adjusting the dose of oxaliplatin if neurotoxicity develops:
- for symptoms of neurotoxicity causing pain lasting more than 7 days, the subsequent dose of oxaliplatin should be reduced from 85 mg/m2 to 65 mg/m2 in the treatment of disseminated colorectal cancer and to 75 mg/m2 in adjuvant therapy;
- in case of paresthesia without functional impairment, which persists until the next cycle, the subsequent dose of oxaliplatin should be reduced from 85 mg/m2 to 65; mg/m for the treatment of metastatic colorectal cancer and up to 75 mg/m for adjuvant therapy;
- in case of paresthesia with functional impairment that persists until the next cycle, oxaliplatin should be discontinued;
- if the severity of symptoms of neurotoxicity decreases after discontinuation of oxaliplatin, you can consider resuming treatment. With the development of stomatitis and/or mucositis of the 2nd or more degree of toxicity, treatment with oxaliplatin should be suspended until they are relieved or the manifestations of toxicity are reduced to grade 1.
Patients with renal failure
There are no data on the use of oxaliplatin in patients with severe renal impairment. Due to limited data regarding the safety and tolerability of the drug in patients with moderate renal impairment, the benefit/risk ratio for the patient should be weighed before using the drug. Therapy in this category of patients can be started with the recommended dose, under careful monitoring of renal function. For mild renal impairment, no dose adjustment of oxaliplatin is required.
Patients with liver failure
No dosage change is required in patients with mild or moderate liver dysfunction. There are no data on the use of oxaliplatin in patients with severe liver dysfunction.
Elderly patients
The safety profile of oxaliplatin as monotherapy or in combination with 5-fluorouracil in patients over 65 years of age is similar to that observed in patients under 65 years of age.
Instructions for preparing the drug solution
When preparing solutions and administering oxaliplatin, do not use needles or other equipment containing aluminum.
Before use, the drug is dissolved in water for injection or in a 5% dextrose solution, obtaining a solution with a concentration of 5 mg/ml oxaliplatin (10 ml of solvent is added to a 50 mg bottle, 20 ml to a 100 mg bottle, 30 ml of solvent to a 150 mg bottle) . The drug thus reconstituted is immediately diluted with 250 - 500 ml of a 5% dextrose solution. The concentration of the resulting oxaliplatin solution should be from 0.2 to 0.7 mg/ml; while 0.7 mg/ml is the highest concentration used in clinical practice at a dose of 85 mg/m2.
To prepare a solution of the drug, only recommended solvents should be used.
The drug should not be used undiluted.
Do not use saline solutions (sodium chloride solution) to dissolve the drug or dilute the drug solution (to prepare an infusion solution). Do not mix in the same container, do not administer simultaneously in the same infusion system with other drugs (especially with 5-fluorouracil, basic solutions, trometamol and folinic acid preparations containing trometamol in their composition).
Oxaliplatin may be given in conjunction with folinic acid infusions. In this case, the drugs should not be mixed in the same infusion container. Folinic acid for infusion should be diluted using a 5% glucose solution, but in no case should solutions containing sodium chloride or alkaline solutions be used.
The prepared solution of the drug should be transparent and should not contain undissolved particles. Otherwise, the drug solution cannot be used. The drug solution is used immediately after preparation.
The drug is intended for single use only. Unused drug solution must be destroyed.
The drug should be injected into the central venous line or into a peripheral vein over 2-6 hours.
In case of extravasation, the drug should be stopped immediately.
Materials used to prepare the solution and its administration must be destroyed in accordance with the rules for the use of cytotoxic drugs.
Use during pregnancy and breastfeeding
Contraindicated during pregnancy and breastfeeding.
Side effects
The most common side effects observed when using oxaliplatin, including in combination with 5-fluorouracil/folinic acid, were gastrointestinal reactions (diarrhea, nausea, vomiting, mucositis), hematological reactions (neutropenia, thrombocytopenia) and neurological reactions. reactions (acute and cumulative dose-dependent peripheral sensory neuropathy). Overall, these side effects were more frequent and severe with the combination of oxaliplatin with 5-fluorouracil/folinic acid compared with 5-fluorouracil and folinic acid alone.
The frequency of adverse reactions listed below is presented in accordance with the following gradation:
very often (> 1/10);
often (> 1/100, < 1/10);
uncommon (> 1/1000, < 1/100);
rare (> 1/10000, < 1/1000);
very rare (<1/10000), including isolated reports.
From the hematopoietic system:
very often - anemia, leukopenia, neutropenia, thrombocytopenia, lymphopenia; often - febrile neutropenia (including grade 3-4), sepsis due to neutropenia; rarely - hemolytic anemia, immune thrombocytopenia.
From the digestive system:
very often - nausea, vomiting, diarrhea, stomatitis, mucositis, stomach pain, constipation, loss of appetite; often - dyspepsia, gastroesophageal reflux, hiccups; infrequently - intestinal obstruction; rarely - colitis, including cases of pseudomembranous colitis.
From the central and peripheral nervous system:
very often - peripheral neurosensory neuropathy, sensitivity disorders, headache, asthenia; often - dizziness, meningism, depression, insomnia; infrequently - increased nervousness; rarely - dysarthria.
Neurotoxicity is a dose-limiting adverse effect. Symptoms of sensory neuropathy are often triggered by cold. The duration of these symptoms, which usually resolve between courses, increases depending on the total dose of oxaliplatin. Functional impairment, which is characterized by difficulty performing precise movements, is a possible consequence of sensory damage. The risk of functional impairment for a total dose of about 850 mg/m2 (10 cycles) is about 10%, reaching 20% in the case of a total dose of 1020 mg/m2 (12 cycles). In most cases, neurological symptoms improve or disappear completely after stopping treatment. However, in 3% of patients 3 years after the end of treatment, either persistent localized paresthesia of moderate intensity (2.3%) or paresthesia affecting functional activity (0.5%) was observed. During treatment with oxaliplatin, acute neurosensory manifestations were noted, which usually occurred within several hours after drug administration and were most often provoked by cold. They were characterized by transient paresthesia, dysesthesia or hypoesthesia, and rarely (1-2%) acute laryngopharyngeal dysesthesia syndrome. The latter was manifested by a subjective feeling of dysphagia and shortness of breath without objective signs of respiratory distress syndrome (cyanosis or hypoxia), or by laryngeal spasm or bronchospasm (without stridor or wheezing). Such phenomena as jaw spasm, tongue dysesthesia, dysarthria and a feeling of pressure in the chest were also observed. Typically, these symptoms were quickly relieved both without the use of drug therapy and with the administration of antihistamines and bronchodilators. Increasing the infusion time during subsequent cycles of oxaliplatin therapy can reduce the incidence of this syndrome.
From the musculoskeletal system:
very often - back pain; often - arthralgia, bone pain.
From the respiratory system:
very often - cough, shortness of breath; often - rhinitis, upper respiratory tract infections; rarely - pulmonary fibrosis.
From the cardiovascular system:
often - chest pain, deep vein thrombophlebitis, pulmonary embolism.
From the urinary system:
often - hematuria, dysuria.
From the skin and skin appendages:
very often - alopecia, skin rashes; often - peeling of the skin of the palms and soles, erythematous rashes, increased sweating, nail disorders.
From the organs of vision and hearing:
often - conjunctivitis, visual impairment; rarely - transient decrease in visual acuity, loss of visual fields, hearing loss, auditory neuritis.
Allergic reactions:
rarely (when used as monotherapy) or often (in combination with 5-fluorouracil +/- calcium folinate), bronchospasm, angioedema, hypotension and anaphylactic shock may occur. Cases of allergic manifestations such as rash (especially urticaria), conjunctivitis or rhinitis have often been reported.
Local reactions:
with extravasation of the drug - pain and inflammatory reactions at the injection site.
From the laboratory parameters:
very often - increased levels of alkaline phosphatase, activity of liver enzymes, bilirubin levels, lactate dehydrogenase, hypokalemia, disturbances in sodium and glucose levels in the blood serum; often - increased creatinine levels.
Other:
very often - increased body temperature, increased fatigue, increased body weight, taste disturbances.
special instructions
Treatment with Oxaliplatin medac should be carried out under the supervision of a physician experienced in the use of cytotoxic drugs. Constant monitoring of possible toxic effects during oxaliplatin therapy is mandatory.
Regularly (once a week), as well as before each administration of the drug Oxaliplatin medac, the formed elements of peripheral blood and indicators of kidney and liver function should be monitored.
Before starting each cycle of therapy with Oxaliplatin medac, a neurological examination should be performed to identify signs of neurotoxicity.
Patients should be informed of the possibility of persistent symptoms of peripheral sensory neuropathy after completion of treatment. Localized moderate paresthesia with functional impairment can last up to 3 years after the end of treatment according to the adjuvant use of the drug.
If symptoms such as dry cough, dyspnea, wheezing or pulmonary infiltrates are detected on X-ray examination, treatment with Oxliplatin medac should be suspended until the presence of interstitial pneumonitis is ruled out.
Symptoms such as dehydration, paralytic ileus, intestinal obstruction, hypokalemia, metabolic acidosis and renal failure may be due to severe diarrhea or vomiting, especially when Oxaliplatin medac is used in combination with 5-fluorouracil.
Patients with a history of allergic reactions to other platinum compounds should be monitored for allergic symptoms. In the event of an anaphylactic-like reaction to oxaliplatin, the infusion should be interrupted immediately and appropriate symptomatic treatment should be instituted. Further use of the drug Oxaliplatin medac in case of allergic reactions is contraindicated. If liver dysfunction or portal hypertension occurs that is not due to liver metastases, the possible presence of drug-induced hepatovascular disorders, which are observed very rarely, should be considered.
In case of extravasation, the infusion should be stopped immediately and local symptomatic treatment should be started. The remaining dose of the drug should be injected into another vein. Women and men should use reliable methods of contraception during treatment and for 6 months after the end of oxaliplatin therapy. When using Oxaliplatin medac, all usual instructions for the use of cytotoxic drugs must be followed. If the lyophilisate or solution of the drug Oxaliplatin medac gets on the skin or mucous membranes, they should be immediately and thoroughly rinsed with water.
Impact on the ability to drive vehicles and other mechanisms that require increased concentration
Not studied. However, the use of oxaliplatin increases the risk of dizziness, nausea, vomiting, and other neurological symptoms that affect the speed of reaction and, thus, reduce the ability to drive a car and use machinery.
Interaction
Pharmaceutically incompatible with alkaline solutions and solutions containing chlorine.
In cases where patients were given a single dose of 85 mg/m2 of oxaliplatin immediately before the administration of 5-fluorouracil, no change in the level of 5-fluorouracil was observed.
There was no noticeable change in the binding of oxaliplatin to plasma proteins in combined in vitro experiments with erythromycin, salicylates, granisetron, paclitaxel and sodium valproate.
Incompatibilities
do not use together with alkaline preparations or solutions (in particular, 5-fluorouracil, alkaline solutions, trometamol and folinic acid preparations containing trometamol as an excipient);
do not use saline solutions to dissolve the drug or dilute the drug solution (to prepare an infusion solution), do not mix with other drugs in the same container or in the infusion system;
do not use administration equipment containing aluminum (precipitate formation may occur and the activity of oxaliplatin may decrease).
Overdose
Symptoms:
increase in the described side effects. No antidote is known.
Treatment:
hematological control and symptomatic therapy.
Best before date
2.5 years.
Storage conditions
Store out of the reach of children and away from light at a temperature not exceeding 25 °C.
Adverse reactions and complications of chemotherapy for tumor diseases
The use of antitumor chemotherapy is often accompanied by adverse reactions. Chemotherapy drugs primarily damage rapidly renewing cells of the digestive tract, bone marrow, hair follicles, etc. In addition, antitumor drugs can damage almost all normal tissues of the body.
There are 5 degrees of severity of side effects of chemotherapy drugs - from 0 to 4.
At grade 0, no changes are observed in the patient’s well-being and research data. With grade 1, there may be minor changes that do not affect the general activity of the patient and do not require medical intervention.
At grade 2, moderate changes are observed that disrupt the patient’s normal activity and vital functions; laboratory data have changed significantly and require correction.
At grade 3, there are severe disturbances that require active treatment, delay or cessation of chemotherapy.
Grade 4 is life-threatening and requires immediate discontinuation of chemotherapy.
The toxic effect of chemotherapy on hematopoiesis is the most common side effect of chemotherapy and is manifested by inhibition of all hematopoiesis. The progenitor cells of leukocytes and platelets are especially often damaged, and less often the cells responsible for the development of red blood cells.
Risk factors for the development of toxic effects of chemotherapy on the bone marrow include: previous chemotherapy and radiation therapy, age of patients over 60 years and under 1 year, general condition of the patient, exhaustion.
Inhibition of hematopoiesis is usually observed in the coming days after the administration of chemotherapy (on days 7-12). Some drugs cause delayed toxic effects.
A sharp and prolonged decrease in the number of leukocytes can lead to an increased incidence of infectious complications. In the last 20 years, there has been an increase in cases of fungal and viral infections.
With a significant decrease in the number of platelets, nosebleeds, gastrointestinal bleeding, cerebral hemorrhages, etc. may occur.
The toxic effect of chemotherapy on the gastrointestinal tract can lead to nausea, vomiting, stomatitis, enteritis and diarrhea (loose stools) as a result of damage to the mucous membranes of the oral cavity and intestines, and toxic damage to the liver.
Nausea and vomiting are not the most dangerous, but the most common and most painful manifestation of the toxic effect of chemotherapy drugs. In some cases, these reactions can even lead to refusal of treatment.
Toxic liver damage is more often detected in patients who have previously had hepatitis or have impaired liver function before the start of chemotherapy.
Cardiotoxicity (damage to the heart muscle) occurs mainly when using anthracyclines (adriamycin, rubomycin) and less often when using other drugs (cyclophosphamide, 5-fluorouracil, etoposide, etc.).
Early manifestations of cardiotoxicity include: decreased blood pressure, rapid heartbeat, rhythm disturbances, and pain in the heart area. Later symptoms of cardiotoxicity occur due to damage to the heart muscle and rhythm disturbances. Sometimes myocardial infarction may occur.
Signs of myocarditis (damage to the heart muscle) are: rapid heartbeat, shortness of breath, enlarged heart, poor circulation.
The development of cardiotoxicity is more often observed in people over 60 years of age, with heart disease, with irradiation of the lungs or mediastinum, with previous chemotherapy with drugs that have cardiotoxicity.
The toxic effect of chemotherapy drugs on lung function is rarely observed. When using bleomycin, the incidence of such a complication (pulmonitis) is 5-20%. The timing of the onset of pulmonitis varies: from several weeks when using bleomycin to 3-4 years when treating with cyclophosphmide and myelosan.
More often, this complication is detected in elderly patients, in patients with lung diseases and previously undergone chemotherapy or radiation.
Damage to the urinary system is due to the fact that most chemotherapy drugs are excreted by the kidneys. The degree of toxicity of drugs depends on their dose and concomitant kidney diseases, as well as on the age of the patient. Renal dysfunction during chemotherapy is most pronounced when using platinum.
Uric acid nephropathy. If the tumor is highly sensitive to chemotherapy, rapid tumor shrinkage (lysis syndrome) may be accompanied by an increase in the level of uric acid in the blood serum and the development of a serious kidney complication - uric acid nephropathy. The initial signs of this complication include: a decrease in the amount of urine, the appearance of a large number of uric acid crystals in the urine sediment, etc.
Allergic reactions can occur in 5-10% of patients when using various chemotherapy drugs. In patients receiving paclitaxel, docetaxel and L-asparaginase, allergic reactions are most common. When using L-asparaginase, allergic reactions are detected in 10-25% of cases.
Neurotoxicity can manifest itself in various parts of the nervous system. In most cases, it is mild, varied and is observed during treatment with many chemotherapy drugs (vincristine, etoposide, prospidine, natulan, platinum, taxol, etc.).
Symptoms of central neurotoxicity most often manifest themselves in the form of impaired attention, memory, emotional disorders, and decreased general tone. The appearance of hallucinations and agitation should be considered serious complications.
Peripheral neurotoxicity manifests itself as mild tingling in the fingers, impaired function of the upper and lower extremities, bloating, blurred vision and hearing.
Neurotoxicity can occur when chemotherapy drugs are injected into the spinal canal or when high doses are used. In this case, patients may experience headaches, dizziness, nausea, vomiting, disturbances in orientation and consciousness.
The toxic effect of chemotherapy on the skin can manifest itself in the form of redness, rash, itching, increased body temperature and decreased sensitivity.
Later, these phenomena can worsen and turn into persistent skin changes with the development of infection, hyperpigmentation of the skin, nails and mucous membranes.
Many skin and nail toxicities resolve on their own soon after chemotherapy is stopped.
Baldness (alopecia) occurs when certain chemotherapy drugs are used that damage the hair follicles. Alopecia is reversible, but is a severe mental trauma, especially for young patients and women. E
This complication often occurs during treatment with doxorubicin, epirubicin, etoposide, taxanes, and other drugs.
Complete hair restoration occurs 3-6 months after the end of chemotherapy.
Toxic fever is most often observed in 60-80% of patients receiving bleomycin. An increase in body temperature also occurs during treatment with L-asparaginase, cytosar, adriamycin, mitomycin C, fluorouracil, etoposide.
The temperature quickly returns to normal and, as a rule, does not cause chemotherapy to be discontinued.
Toxic phlebitis (inflammation of the veins) develops more often after several injections of drugs and is manifested by: severe pain along the veins during the administration of chemotherapy, thrombosis and blockage of the veins.
Most often, toxic phlebitis develops during treatment with embiquin, cytosar, vinblastine, dactinomycin, doxorubicin, rubomycin, epirubicin, dacarbazine, mitomycin C, taxanes, nevelbine and with repeated injections of drugs into the same vein.
The local toxic effect of chemotherapy drugs occurs when some of them (nitrosourea derivatives, doxorubicin, rubomycin, vincristine, vinblastine, mitomycin C, dactinomycin, etc.) get under the skin during intravenous administration. As a result, necrosis (death) of the skin and underlying tissues is possible. Late complications of chemotherapy are uncommon. They develop over a year or longer after chemotherapy.
The most dangerous complications of chemotherapy include: osteoporosis (bone loss), damage to the mucous membrane of the bladder and the emergence of new (second) malignant tumors.
In later stages, it is also possible to develop persistent suppression of the bone marrow, immune system, gonadal function, and damage to the heart and lungs.
In children treated with cyclophosamide, methotrexate, dactinomycin, adriamycin and hormones, growth and development disorders may occur
Oxaliplatin-Teva concentrate for preparations. solution for infusion 5 mg/ml 10 ml bottle in Moscow
Intravenously, as an infusion over 2–6 hours. Oxaliplatin-Teva is prescribed only to adults. Hyperhydration is not required when using the drug. If Oxaliplatin-Teva is used in combination with fluorouracil, an infusion of Oxaliplatin-Teva should precede the administration of fluorouracil.
Adjuvant therapy for colorectal cancer - 85 mg/m2 once every 2 weeks for 12 cycles (6 months).
Treatment of disseminated colorectal cancer - 85 mg/m2 once every 2 weeks as monotherapy or in combination with fluorouracil.
Treatment of ovarian cancer - 85 mg/m2 once every 2 weeks as monotherapy or in combination with other chemotherapy drugs.
Repeated administrations of Oxaliplatin-Teva are carried out only when the number of neutrophils is more than 1.5·109/l and platelets more than 50·109/l.
Recommendations for dose adjustment and administration of oxaliplatin
In case of hematological disorders (number of neutrophils <1.5x109/l and/or platelets <50·109/l), the next course is postponed until normal laboratory parameters are restored.
With the development of diarrhea of grade IV toxicity (according to the WHO scale), neutropenia of grade III–IV (neutrophil count <1·109/l), thrombocytopenia of grade III–IV (platelet count 50·109/l), the dose of Oxaliplatin-Teva during subsequent administrations should be reduced from 85 to 65 mg/m2 - for the treatment of disseminated colorectal and ovarian cancer; up to 75 mg/m2 - for adjuvant therapy of colorectal cancer in addition to the usual reduction in the dose of fluorouracil in the case of their combined use.
For patients who develop acute laryngopharyngeal dysesthesia during the infusion or within several hours after a 2-hour infusion, the next infusion of Oxaliplatin-Teva should be administered within 6 hours.
If pain appears (as a sign of neurotoxicity) lasting more than 7 days or paresthesia without functional impairment that persists until the next cycle, the subsequent dose of Oxaliplatin-Tev should be reduced by 25%.
In case of paresthesia with functional impairment that persists until the next cycle, Oxaliplatin-Teva should be discontinued; if the severity of symptoms of neurotoxicity decreases after discontinuation of Oxaliplatin-Tev, the issue of resuming treatment can be considered.
With the development of stomatitis and/or mucositis of grade II or more, treatment with Oxaliplatin-Teva should be suspended until they are relieved or toxicity is reduced to grade I.
Patients with renal failure. There are no data on the use of oxaliplatin in patients with severe renal impairment. Due to limited data regarding the safety and tolerability of the drug in patients with moderate renal impairment, the benefit/risk ratio for the patient should be weighed before using the drug. Therapy in this category of patients can be started with the recommended dose, under careful monitoring of renal function. For mild renal impairment, no dose adjustment of oxaliplatin is required.
Patients with liver failure. No change in dosage regimen is required in patients with mild or moderate liver failure. There are no data on the use of oxaliplatin in patients with severe liver dysfunction.
Elderly patients. No dosage adjustment is required when prescribing oxaliplatin to patients over 65 years of age (including when used in combination with fluorouracil).
Rules for preparing and administering the solution
When preparing and administering Oxaliplatin-Tev, do not use needles or other equipment containing aluminum.
To prepare an infusion solution, oxaliplatin is diluted with 250–500 ml of a 5% dextrose solution. The concentration of the resulting oxaliplatin solution should be from 0.2 to 0.7 mg/ml; while 0.7 mg/ml is the highest concentration used in clinical practice at a dose of 85 mg/m2.
To prepare a solution of the drug, only recommended solvents should be used.
The drug should not be used undiluted.
Do not use 0.9% sodium chloride solution or other saline solutions to dissolve the drug or dilute the drug solution (to prepare an infusion solution).
Do not mix in the same container and do not administer simultaneously in the same infusion system with other drugs (especially fluorouracil, trometamol and calcium folinate preparations containing trometamol), alkaline solutions or solutions containing chlorides.
Oxaliplatin can be prescribed in conjunction with calcium folinate infusions. In this case, the drugs should not be mixed in the same infusion container. Calcium folinate for infusion should be diluted using a 5% dextrose solution, but in no case should solutions containing sodium chloride or alkaline solutions be used.
The prepared solution of the drug should be transparent and should not contain undissolved particles. Otherwise, the drug solution cannot be used.
The drug solution is used immediately after preparation and is intended for single use only. Unused drug solution must be destroyed.
In case of extravasation, the drug should be stopped immediately.
