Index of drugs

In combination with 5-fluorouracil (5-FU) and folinic acid: supportive therapy for stage III colon cancer (C on the Dukes scale) after complete resection of the primary tumor; treatment of colorectal cancer with metastases.

1 ml concentrate for solution for infusion contains 5 mg of oxaliplatin; drug contains lactose.

An anti-cancer drug, a platinum derivative. Hydrated derivatives formed as a result of biotransformation of oxaliplatin, disrupt the DNA helix, forming cross-links both within one strand and between them, resulting in the disruption of DNA synthesis leading to cytotoxic and antitumor effects. Oxaliplatin has activity in various models resistant to cisplatin. A synergistic cytotoxic effect was observed when oxaliplatin was used in combination with 5-fluorouracil. At the end of the 2-hour infusion, 15% of platinum is in the circulation, 85% penetrates into the tissues or is excreted in the urine. Oxaliplatin is irreversibly bound to erythrocytes and serum albumin, hence T_0,5 in these matrices it is close to the natural transformation period of red blood cells or albumin. Oxaliplatin is extensively subject to biotransformation in the body, to numerous cytotoxic metabolites and numerous inactive conjugated compounds. Biotransformation proceeds without the participation of enzymes. Excretion occurs mainly in the urine, with renal clearance mainly within 48 h after drug administration. After 5 days, about 54% of the total dose of the drug is detected in the urine and less than 3% in the faeces.

Hypersensitivity to oxaliplatin or any of the excipients. Myelosuppression before the first course of treatment: neutrophil count <2 x 10⁹/ l and (or) platelet count <100 x 10⁹/ L. Peripheral sensory neuropathy with functional impairment prior to the first course of treatment. Severe renal impairment (creatinine clearance <30 ml / min). Breastfeeding period.

In patients with moderate renal impairment, oxaliplatin should be considered after the benefit-risk assessment of the patient; in such cases, renal function should be closely monitored and the dose adjusted depending on the symptoms of toxicity. Patients with a history of hypersensitivity to platinum compounds should be observed for the appearance of allergy symptoms, and if hypersensitivity reactions occur, oxaliplatin should be discontinued and appropriate symptomatic treatment should be initiated; re-administration of oxaliplatin is contraindicated in these patients. The toxicity of oxaliplatin to the gastrointestinal tract requires prophylactic and / or therapeutic administration of antiemetics. Due to the neurotoxicity of oxaliplatin, neurological examinations should be performed prior to each dose administration and periodically after administration of the dose; this applies especially to patients taking other drugs with neurotoxic effects. In case of acute throat and larynx sensation during the infusion lasting 2 h or a few hours after its completion, the Next dose of oxaliplatin should be given as an infusion lasting 6 h. In the event of neurological symptoms (paraesthesia, sensory disturbances) the dose of oxaliplatin should be modified, depending on the duration and severity of symptoms: if the symptoms last longer than 7 days and are troublesome, the next dose should be reduced from 85 to 65 mg / m² pc. (treatment of cancer with metastases) or 75 mg / m² pc. (complementary treatment); if paresthesia persists without functional disorder until the next course of treatment, the next dose should be reduced from 85 to 65 mg / m² pc. (treatment of cancer with metastases) or 75 mg / m² pc. (complementary treatment); if paraesthesia with functional disorder persists until the next course of treatment, oxaliplatin should be discontinued - after discontinuation of symptoms after discontinuation of oxaliplatin therapy, resumption of therapy may be considered. If you observe rapidly progressing neurological disorders, including seizures, hypertension, headache, confusion, loss of vision and other visual disturbances, consideration should be given to identifying the reversible posterior leukoencephalopathy syndrome (RPLS) using brain imaging, preferably magnetic resonance imaging (MRI). A full blood count with a smear should be performed before starting oxaliplatin therapy and before each treatment cycle. If signs of haematological toxicity occur: neutrophil count <1.5 x 10⁹/ l or platelet count <50 x 10⁹/ l, the next treatment cycle should be delayed until the haematological parameters return to normal values. In case of oral mucositis with or without neutropenia, the next treatment cycle should be delayed until the symptoms of inflammation subside (to grade 1 or less) and / or an increase in the neutrophil count to a value of 1.5 x 10⁹/ L. When oxaliplatin is administered in combination with 5-fluorouracil (5-FU), standard dosing modifications should be followed when toxicity associated with 5-FU occurs. If grade 4 diarrhea occurs, grade 3 to 4 neutropenia (neutrophil count <1.0 x 10)⁹/ l) or thrombocytopenia in the 3rd to 4th degree (platelets <50 x 10⁹/ l) reduce the dose of oxaliplatin from 85 to 65 mg / m² pc. (treatment of cancer with metastases) or 75 mg / m² pc. (complementary treatment); the 5-FU dose should also be reduced accordingly. If unexplained respiratory symptoms, such as cough without discharge, dyspnea, crescents or pulmonary infiltrates in an X-ray, occur, oxaliplatin should be discontinued until either interstitial lung disease or pulmonary fibrosis is ruled out. In case of abnormal results of liver function tests or portal hypertension, which do not necessarily result from hepatic metastases to the liver, the possibility of developing hepatic vasopathy due to the treatment should be taken into account.

The drug should not be used during pregnancy, especially in the first trimester. Administration of oxaliplatin may only be considered after an assessment of the benefit / risk ratio and obtaining the consent of the patient. Women should use effective contraception during oxaliplatin treatment and for 4 months after treatment. Men should avoid conceiving a child during treatment with oxaliplatin and for 6 months after its completion. Before starting treatment, the patient should be informed about the possibility of sperm preservation due to the possibility of irreversible infertility due to treatment. The use of oxaliplatin during breastfeeding is contraindicated.

The most common side effects of oxaliplatin in combination with 5-FU and / or folinic acid are gastrointestinal disorders, haematological and nervous system disorders. Side effects are more common and are more severe when using oxaliplatin in combination with 5-FU and folinic acid than when using 5-FU and / or folinic acid as monotherapy. Very common: infection, anemia, neutropenia, thrombocytopenia, leukopenia, lymphopenia, allergy, allergic reactions (frequent allergic reactions: skin rash, especially urticaria, conjunctivitis, rhinitis, frequent anaphylactic reactions: bronchospasm, chest pain , angioneurotic edema, hypotension, anaphylactic shock), anorexia, abnormal blood Glucose, hypokalaemia, abnormal blood sodium levels, peripheral sensory neuropathy, sensory disturbances, dysgeusia, headache, epistaxis, dyspnoea, cough, diarrhea, nausea , vomiting, stomatitis and / or mucositis, abdominal pain, constipation, abnormal skin, alopecia, back pain, fever (very often fever and chills due to infection as well as due to the immune mechanism), fatigue, weakness, pain, reaction at the site of administration (local pain, redness, o clash, thrombosis, extravasation may cause local pain and inflammatory reaction, which can be serious and lead to complications, especially when oxaliplatin is administered through the peripheral vein), increased liver enzymes, alkaline phosphatase in the blood, increased bilirubin in the blood, increased lactate dehydrogenase activity in the blood; weight gain (complementary treatment). Common: rhinitis, upper respiratory tract infection, febrile neutropenia, neutropenic sepsis, dehydration, depression, insomnia, dizziness, inflammation of the motor nerves, meningitis, conjunctivitis, blurred vision, hemorrhage, flushing, thrombophlebitis deep veins, pulmonary embolism, chest pain, hypertension, hiccups, indigestion, gastro-oesophageal reflux, gastrointestinal bleeding, rectal bleeding, exfoliation (hand-foot syndrome), erythematous rash, rash, increased sweating, changes in the nails, joint pain, bone pain, hematuria, painful or difficult urination, impaired urinary frequency, increased blood creatinine; weight loss (treatment of cancer with metastases). Uncommon: metabolic acidosis, nervousness, ototoxicity, intestinal obstruction, intestinal torsion.Rare: autoimmune thrombocytopenia, haemolytic anemia, speech disorder, reversible posterior leukoencephalopathy syndrome (RPLS), transient worsening of visual acuity, visual field disorders, optic neuritis, transient loss of vision (reversible after discontinuation of treatment), deafness, interstitial lung disease (sometimes leading to to death), pulmonary fibrosis, colitis (including diarrhea induced byClostridium difficile), inflammation of the pancreas. Very rare: hepatic sinus syndrome or pathological symptoms (associated with liver disorders such as hepatic purpura, regenerative nodular hypertrophy, fibrosis around the hepatic sinuses, portal hypertension and / or elevation of aminotransferases), acute renal tubulopathy, acute interstitial nephritis and acute renal failure. Not known: haemolytic uremic syndrome, convulsions. Moderate paraesthesia or paresthesias that affect patient activity may persist for up to 3 years after completion of adjuvant therapy. Severe diarrhea and / or vomiting, especially when oxaliplatin is given in combination with 5-FU, may result in dehydration, paralytic ileus, intestinal obstruction, hypokalaemia, metabolic acidosis and renal dysfunction.

Intravenously. Only in adults. Use only in specialized cancer departments and administered under the supervision of an experienced oncologist. The recommended dose of oxaliplatin for the treatment of metastatic colorectal cancer and metastatic treatment is 85 mg / m² pc. every 2 weeks. Complementary treatment is carried out for 12 cycles (6 weeks). The dose should be adjusted depending on the individual patient's tolerance.Special groups of patients. No dose adjustment is required in patients with mild renal impairment; in patients with moderate renal impairment, treatment can be started at the usual recommended dose by monitoring the treatment; Do not use in patients with severe renal impairment. The oxaliplatin dose was not changed during clinical trials in patients with abnormal liver function tests. There is no need to adjust the dose in the elderly.Way of giving. Oxaliplatin is administered as an intravenous infusion lasting 2-6 h, through a central or peripheral vein, in 250-500 ml of a 5% Glucose solution to obtain a concentration of 0.2-0.70 mg / ml (concentration 0.70 mg / ml is the highest concentration used in clinical practice for an oxaliplatin dose of 85 mg / m²). The oxaliplatin infusion must always precede the administration of 5-FU. Administration of oxaliplatin does not require excessive hydration of the patient. In the case of extravasation, the infusion should be stopped immediately and the usual topical symptomatic treatment initiated.