Index of drugs

Supplementary treatment of Grade II colon cancer (Duke C) after complete resection of the primary tumor and treatment of metastatic colorectal cancer in combination with 5-fluorouracil and folinic acid.

1 ml concentrate for solution for infusion contains 5 mg of oxaliplatin (vial with a capacity of 10 ml, 20 ml or 40 ml contains respectively 50 mg, 100 mg or 200 mg oxaliplatin).

An anti-cancer drug, a platinum derivative. Oxaliplatin has a broad spectrum of cytotoxic activityin vitro and acts anti-cancerin vitro in different layouts of model tumors. In addition, it has activityin vitro andin vivo in various models resistant to cisplatin. Both in vitro, how in vivo a synergistic cytotoxic effect was observed when using the drug in combination with 5-fluorouracil. Research into the mechanism of action of oxaliplatin, although it is not fully elucidated, has shown that hydrated derivatives, resulting from the biotransformation of oxaliplatin, interact with DNA, resulting in cross-linked bonds, both inside and between the DNA chains, causing interruption of DNA synthesis. Oxaliplatin is extensively subject to biotransformation in the body, to numerous cytotoxic metabolites and numerous inactive conjugated compounds. It is excreted mainly in the urine, with a 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. Breastfeeding period. Bone marrow suppression 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).

The drug should only be used in specialized cancer departments; drug should be administered under the supervision of an experienced oncologist. 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 its toxic effects. Patients with an allergic reaction to a history of platinum compounds should be observed for the appearance of allergy symptoms, and if anaphylaxis-like reaction occurs after oxaliplatin administration, discontinue administration and appropriate symptomatic treatment. In these patients, re-administration of oxaliplatin is contraindicated. The toxicity of oxaliplatin to the gastrointestinal tract requires prophylactic and / or therapeutic administration of antiemetics. In the event of extravasation, the infusion should be immediately stopped and topical symptomatic treatment should be given. Due to the neurotoxic effect of the drug, a neurological examination should be carried out each time before the Next dose of the drug and periodically after its administration. This is especially true for patients who are taking other neurotoxic drugs. In case of acute throat and laryngeal dysfunction during and after an infusion lasting 2 hours, the next dose of oxaliplatin should be infused over an intravenous infusion over 6 hours. If nervous system symptoms occur (hyperaesthesia, sensory disturbances), the oxaliplatin dose 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); in the event of persistence of hyperalgesia without functional disorder until the next treatment cycle, 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 hyperesthesia with functional disorder persists until the next treatment cycle, administration of oxaliplatin should be discontinued.After the symptoms have resolved after discontinuation of oxaliplatin therapy, re-administration may be considered. Patients should be advised about the possibility of persistent peripheral sensory neuropathy after treatment. If haematological changes occur (neutrophil count <1.5 x 10)⁹/ l or platelet count <50 x 10⁹/ l) delay the next treatment cycle until the hematology parameters return to normal values. In the event of mucositis and / or stomatitis with or without neutropenia, the next treatment cycle should be delayed until the mucosal inflammation and / or stomatitis (to grade 1 or less) and / or increase in the number of neutrophils up to ≥ 1.5 x 10⁹/ L. When administering oxaliplatin in combination with 5- Fluorouracil, the dose adjustments should be followed depending on the onset of symptoms of 5-fluorouracil toxicity. 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 dose of 5-fluorouracil should also be reduced accordingly. In the case of unexplained respiratory symptoms, such as cough without secretion, dyspnoea, crepitations or X-ray in the lungs, oxaliplatin should be discontinued until further testing, which excludes the presence of interstitial lung disease or pulmonary fibrosis. In the event of abnormal results of liver function tests or portal hypertension, which can not be attributed to the presence of liver metastases, very rare cases of hepatic vascular disorders should be considered.

The medicine should not be used during pregnancy and in women of childbearing potential not using contraception. Appropriate contraception should be used during treatment and for 4 months after completion of treatment in women and 6 months in men. Breast feeding during oxaliplatin treatment is contraindicated. Treatment with oxaliplatin may cause irreversible infertility - the patient should be informed about the possibility of semen storage before starting treatment.

The most commonly reported adverse reactions when using oxaliplatin in combination with 5-fluorouracil and / or folinic acid were gastrointestinal disorders (diarrhea, nausea, vomiting, mucositis), blood and hematopoietic system (neutropenia, thrombocytopenia) and on the part of the system nervous (peripheral sensory neuropathy). Side effects were more frequent and more severe when oxaliplatin was used in combination with 5-fluorouracil and folinic acid than when 5-fluorouracil and / or folinic acid was used as monotherapy. Very common (≥1 / 10): increase in liver enzymes, increase in alkaline phosphatase in the blood, increase in bilirubin in the blood, increase in blood lactate dehydrogenase, weight gain (adjuvant treatment), anemia, neutropenia, thrombocytopenia, leukopenia, lymphopenia, peripheral sensory neuropathy, sensory disturbances, taste disorders, headache, shortness of breath, cough, nausea, diarrhea, vomiting, stomatitis and / or mucositis, abdominal pain, constipation, skin disease, alopecia, back pain, anorexia , abnormal blood Glucose, hypokalaemia, abnormal blood sodium levels, infection, nosebleeds, tiredness, fever (very often fever and chills (tremors) due to infection (with or without neutropenia) or possibly with an immune mechanism), weakness, pain, reaction at the injection site (local pain, rupture It can lead to local pain and inflammation, which can be serious and lead to complications, including necrosis, especially when oxaliplatin is administered through the peripheral vein), allergy and / or allergic reactions (frequent allergic reactions: skin rash (especially urticaria, conjunctivitis, rhinitis; frequent anaphylactic reactions: bronchospasm, chest pain, angioneurotic edema, hypotension, anaphylactic shock).Common (≥1 / 100, <1/10): increase in blood creatinine, weight loss (treatment of cancer with metastases), dizziness, inflammation of the motor nerves, meningitis, conjunctivitis, visual disturbances, hiccups, indigestion, reflux gastroesophageal, bleeding from the stomach and intestines, rectal haemorrhage, hematuria, painful, difficult urination, impaired urinary frequency, peeling of the skin (hand-foot syndrome), erythema with erythema, rash, increased sweating, changes within nails, joint pain, bone pain, dehydration, rhinitis, upper respiratory tract infection, febrile neutropenia and / or neutropenic sepsis, haemorrhage, sudden redness of the face, deep vein thrombosis, pulmonary embolism, hypertension, depression, insomnia, allergic reactions (such as skin rash, urticaria, conjunctivitis, rhinitis), anaphylactic reactions (bronchospasm, chest pain, angioneurotic edema, hypotension, anaphylactic shock). Uncommon (≥1 / 1000, <1/100): ototoxicity, intestinal obstruction, intestinal obstruction, metabolic acidosis, nervousness. Rare (≥1 / 10,000, 1/1000): autoimmune thrombocytopenia, haemolytic anemia, dysarthria, transient worsening of visual acuity, visual field disorders, optic neuritis, loss of vision transient at the end of treatment, deafness, interstitial lung disease (sometimes with the effect of fatal), pulmonary fibrosis, colitis (including diarrhea induced byClostridium difficile). Very rare (<1 / 10,000): obstructive sinus syndrome or pathological symptoms associated with liver disorders such as (hepatic thrombosis, regenerative nodular hypertrophy, fibrosis around the hepatic sinuses, portal hypertension and / or transaminase elevation), acute tubular-interstitial nephropathy leading to acute renal failure. In addition, post-marketing experience (unknown incidence) was observed: haemolytic uraemic syndrome, seizures. Severe diarrhea and / or vomiting, especially when oxaliplatin is given in combination with 5-fluorouracil, may result in dehydration, paralytic ileus, other intestinal obstruction, hypokalaemia, metabolic acidosis and renal dysfunction. Moderate paraesthesia or paresthesias that affect patient activity may persist for up to 3 years after completion of adjuvant therapy.

Intravenously, only in adults. The recommended dose of oxaliplatin in the treatment of metastatic and metastatic colorectal cancer 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 patient's tolerance. Oxaliplatin should always be administered before fluoropyrimidine derivatives, e.g. 5-fluorouracil.
The drug is administered as an intravenous infusion lasting 2-6 h, through a central or peripheral vein. The solution for infusion is prepared in 250-500 ml of a 5% Glucose solution, to obtain a concentration of the drug within 0.2-0.7 mg / ml (concentration 0.7 mg / ml is the highest concentration in clinical practice at the dose of 85 mg / m² pc.).
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. 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.