Expiration date: 05/2025

Composition and form of issue:
Concentrate for preparation of solution for infusions of 1 ml
oxaliplatin 5 mg
excipients: lactose monohydrate water for injection   
in bottles of 10 or 20 ml in a pack of cardboard 1 bottle, Packed in PE film.
Description of dosage form:
Transparent colorless or almost colorless solution with a yellowish tinge.
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, with 15% of the injected platinum in the blood, and the remaining 85% are rapidly distributed to tissues or excreted by the kidneys. Platinum binds to plasma albumin and excreted in the urine during the first 48 no. to the 5th day about 54% of the total dose is found in the urine and less than 3% — in the feces. In renal insufficiency, there is a significant decrease in Cl oxaliplatin C (17, 55±2, 18) l / h to (9, 95±1, 91) l/h. The effect of severe renal failure on platinum clearance has not been studied.
Description of pharmacological action:
Oxaliplatin is an antitumor drug belonging to a new class of platinum-based compounds in which the platinum atom forms a complex bond with 1, 2-diaminocyclohexane (DASG) and oxalate group.
Oxaliplatin has antitumor activity in various types of tumors, including colorectal cancer. It is also effective in the treatment of tumors resistant to cisplatin. The action is manifested regardless of the phase of the cell cycle. When applying fluorouracil has been observed synergism of cytotoxic effect. The mechanism of the antitumor effect of oxaliplatin is based on cytotoxic action and has not been fully studied. Presumably, oxaliplatin forms inter-and intra-binding bonds with DNA, thereby inhibiting the phase of its replication and transcription.
Indications:

• adjuvant therapy of stage III colorectal cancer (Duke) after radical resection of the primary tumor in combination with fluorouracil / calcium folinate
• disseminated colorectal cancer (as monotherapy or combination therapy with fluorouracil / calcium folinate)
• ovarian cancer (as a second-line therapy).

Contraindications:

• hypersensitivity to oxaliplatin, other platinum derivatives or other components of the drug
• myelosuppression before the first course of therapy (at the level of neutrophils less than 2·109/l and / or platelets less than 100·109/l)
• peripheral sensory neuropathy with functional disorders before the first course of therapy
• severe renal impairment (creatinine Cl less than 30 ml / min)
• pregnancy
• lactation
• childhood.

With caution: in violation of renal function, severe hepatic impairment.
Side effect:
The frequency of adverse reactions listed below was determined according to the following criteria: very often (>,1/10), often (>,1/100, 1/1000, 1/10000, from the hematopoietic system:very often — anemia, leukopenia, neutropenia, thrombocytopenia, lymphopenia often — febrile neutropenia (including 3-4-th degree), sepsis against the background of neutropenia rarely — hemolytic anemia, immune thrombocytopenia.From the digestive system: very often — nausea, vomiting, diarrhea, stomatitis/ mucositis, abdominal pain, constipation, loss of appetite often — dyspepsia, gastro-esophageal reflux, intestinal bleeding, hiccups, metabolic acidosis, pancreatitis infrequently — paralytic ileus, intestinal obstruction rarely — colitis, including cases of pseudomembranous colitis.
On the part of the hepatobiliary system: very rarely — sinusoidal obstruction of portal blood flow, liver peliosis, nodular regenerative hyperplasia of hepatic tissue, perisinusoidal fibrosis clinically complications are manifested by portal hypertension and/or increased activity of hepatic transaminases.
From the nervous system: very often — peripheral sensory neuropathy, sensitivity disorders, headache, asthenia often — dizziness, meningism, depression, insomnia, infrequently — increased nervousness rarely — dysarthria, convulsions. Neurotoxicity is a dose-limiting factor. Often symptoms of sensory neuropathy are provoked by cold. The duration of these symptoms, which are usually stopped between courses, increases depending on the total dose of oxaliplatin. Functional disorders in the form of difficulty in performing precise movements are possible consequences of sensory damage. The risk of functional disorders at 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). After discontinuation of treatment in most cases, the severity of neurological symptoms decreases, or they are completely stopped. In 3% of patients, 3 years after the end of treatment, either stable local paresthesia of moderate intensity (2, 3%) or paresthesia affecting functional activity (0, 5%) were observed. During treatment with oxaliplatin, acute neurosensory manifestations were noted, which usually occurred within a few hours after administration of the drug and were most often provoked by the influence of cold. They were characterized by transient paresthesia, dysesthesia or hypesthesia, rarely (1-2%) — acute syndrome of laryngeal-pharyngeal dysesthesia. The latter manifested itself as a subjective feeling of dysphagia and shortness of breath without objective signs of respiratory distress syndrome (cyanosis or hypoxia) or laryngeal spasm or bronchospasm (without stridor or wheezing). There were also such phenomena as spasm of the jaw muscles, dysesthesia of the tongue, dysarthria and a feeling of pressure in the chest. Usually, these symptoms were quickly stopped without the use of drug therapy, and with the introduction of antihistamines and bronchodilators. Increasing the duration of infusion in subsequent cycles of therapy with oxaliplatin can reduce the frequency of this syndrome.
From the side of musculoskeletal system:often — pain in the back often — artralgia, pain in the bones.
From the respiratory system: very often — cough, shortness of breath often — rhinitis, upper respiratory tract infections, chest pain rarely — interstitial pneumonia, pulmonary fibrosis.
From the cardiovascular system: often-chest pain, deep vein thrombophlebitis,pulmonary embolism.
From the urinary system: often-hematuria, dysuria, hemolytic uremic syndrome, acute tubular necrosis, acute interstitial nephritis, acute renal failure.
From the skin and skin appendages: very often — alopecia, skin rashes often-peeling of the skin of the palms and feet, erythematous rashes, increased sweating, changes from the nails.
From the organs of vision and hearing:often — conjunctivitis, visual impairment rarely — transient reduction in visual acuity, loss of visual fields, optic neuritis, hearing loss, auditory nerve neuritis.
Allergic reactions: rarely (when used as monotherapy) or often (in combination with fluorouracil and calcium folinate) can be observed bronchospasm, angioedema, lowering blood pressure, anaphylactic shock. Often there have been cases of such allergic reactions, like rash (particularly urticaria), conjunctivitis, or rhinitis.
Local reactions: when extravasation of the drug-redness, pain and inflammatory reactions at the site of administration.
From the laboratory indicators: very often — hypokalemia, hyponatremia, hyperglycemia, increased levels of thyroid gland activity of hepatic enzymes, bilirubin, lactate dehydrogenase often — increase in creatinine.
Other:very often — increased body temperature, increased fatigue, increased body weight, disturbance of taste, nose bleeding.
Drug interaction:
Significant changes in the binding of oxaliplatin to plasma proteins while the use of erythromycin, salicylates, granisetron, paclitaxel and valproic acid was not observed.
When interacting with aluminum, the formation of sediment and a decrease in the activity of oxaliplatin.
Oxaliplatin-Teva is pharmaceutically incompatible with 0, 9% sodium chloride solution and other solutions containing chlorides, as well as alkaline solutions.

Dosage and administration:
In/in, in the form of infusion for 2-6 hours Oxaliplatin-Teva appoint only adults. Hyperhydration when using the drug is not required. If Oxaliplatin-Teva is used in combination with fluorouracil, oxaliplatin-Teva infusion should precede the introduction of fluorouracil.
Adjuvant therapy of colorectal cancer-85 mg / M21 times in 2 weeks for 12 cycles (6 months).
Treatment of disseminated colorectal cancer-85 mg / M21 times in 2 weeks as monotherapy or in combination with fluorouracil.
Treatment of ovarian cancer-85 mg / M21 every 2 weeks as monotherapy or in combination with other chemotherapy drugs.
Repeated administration of Oxaliplatin-Teva produce only when the number of neutrophils more than 1, 5 * 109/l and platelets more than 50·109/l.
Recommendations for dose adjustment and administration of oxaliplatin
In hematological disorders (the number of neutrophils 9/l and/or platelets 9/l), the next course is postponed until the restoration of normal laboratory parameters.With the development of diarrhea IV degree of toxicity (on a who scale), neutropenia III-IV degree (number of neutrophils 9/l), thrombocytopenia III–IV degree (number of platelets 50·109/l) dose Oxaliplatin-Teva with subsequent administration should be reduced from 85 to 65 mg / m2-in the treatment of disseminated colorectal cancer and ovarian cancer to 75 mg / m2— in adjuvant therapy of colorectal cancer in addition to the usual reduction in the dose of fluorouracil in the case of their combined use.Patients who during infusion or within a few hours after 2-hour infusion develops acute laryngeal-pharyngeal dysesthesia, the next infusion of Oxaliplatin-Teva should be carried out within 6 hours.
In case of pain (as a sign of neurotoxicity) lasting more than 7 days or paresthesia without functional disorders, remaining until the next cycle, the subsequent dose of Oxaliplatin-Teva should be reduced by 25%.
In paresthesia with functional disorders that persist until the next cycle, Oxaliplatin-Teva should be canceled with a decrease in the severity of neurotoxicity symptoms after the abolition of Oxaliplatin-Teva, it is possible to consider resuming treatment.
With the development of stomatitis and / or mucositis II and more toxicity, treatment with Oxaliplatin-Teva should be suspended until their relief or reduce the manifestations of toxicity to the I degree.
Patients with renal insufficiency.Data on the use of oxaliplatin in patients with severe renal impairment no. Due to the limited data on the safety and tolerability of the drug in patients with moderate renal impairment, before using the drug should weigh the benefit/risk ratio for the patient. Therapy in this category of patients can be started with the recommended dose, under careful control of renal function. With a mild degree of renal dysfunction dose correction oxaliplatin is not required.
Patients with insufficiency of liver function.Changes in the dosage regimen in patients with mild or moderate liver failure is not required. There are no data on the use of oxaliplatin in patients with severe liver dysfunction.
Elderly patient.No correction of dosing regimen in the appointment of oxaliplatin patients over the age of 65 years (including when used in combination with fluorouracil).
Rules of preparation and administration of the solution
In the preparation and administration of Oxaliplatin-Teva can not use needles and other equipment containing aluminum.
For the preparation of the intravenous solution oxaliplatin is diluted with 250-500 ml of 5% dextrose solution. The concentration of the resulting oxaliplatin solution should be from 0, 2 to 0, 7 mg/ml with 0, 7 mg/ml — the highest concentration used in clinical practice at a dose of 85 mg / m2.
To prepare the solution of the drug should be applied only with the recommended solvent.
Do not use the drug undiluted.
Do not use for dissolution of the drug or dilution of the drug solution (for preparation of infusion solution) 0, 9% sodium chloride solution and other salt solutions.
Do not mix in one container and do not prescribe simultaneously in one infusion system with other drugs (especially fluorouracil, trometamol and calcium folinate preparations containing trometamol in their composition), 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 a single infusion container. Calcium folinate for infusion should be diluted using a 5% dextrose solution, but in any case should not be used solutions containing sodium chloride or alkaline solutions.
The prepared solution of the preparation should be transparent and should not contain undissolved particles. Otherwise, the drug solution can not be used.
The solution of the drug is used immediately after preparation and it is intended only for single use. Unused solution of the drug should be destroyed.
In case of extravasation, the drug administration should be stopped immediately.
Overdose:
Symptoms: myelosuppression, neurotoxicity, diarrhea, nausea, vomiting.
Treatment: hematological control and symptomatic therapy. The antidote to oxaliplatin is unknown.
Special instruction:
Oxaliplatin-Teva should be used only under the supervision of an oncologist who has experience with anticancer drugs.
Regularly (once a week), as well as before each administration of the drug should be monitored form elements of peripheral blood and indicators of kidney and liver function.
Before each injection and during treatment should be carried out neurological examination of patients for signs of neurotoxicity, especially in the case of Oxaliplatin-Teva with other medicines that have a specific toxic effect on the nervous system. Patients should be informed about the possibility of preserving the symptoms of peripheral sensory neuropathy after the end of treatment. Localized moderate paresthesia with functional disorders can persist up to 3 years after the end of the drug for adjuvant therapy.
With the appearance of respiratory symptoms (dry cough, dyspnea, wheezing or detection of pulmonary infiltrates in x-ray examination), treatment with Oxaliplatin-Teva should be suspended until the presence of interstitial pneumonitis is excluded. Symptoms such as dehydration, paralytic ileus, bowel obstruction, hypokalemia, metabolic acidosis and renal failure may be due to severe diarrhea or vomiting, especially when Oxaliplatin-Teva is used in combination with fluorouracil.
Patients with allergic reactions to other platinum compounds in history should be monitored for allergic symptoms. In the case of a reaction to Oxaliplatin-Teva, such anaphylactic, infusion should be immediately interrupted and appropriate symptomatic treatment. Further use of Oxaliplatin-Teva in the case of allergic reactions is contraindicated.
In case of extravasation, the infusion should be stopped immediately and local symptomatic treatment should be started. The remaining dose should be injected into another vein. Women and men during treatment with Oxaliplatin-Teva and within 6 months after the end of therapy with Oxaliplatin-Teva should use reliable methods of contraception.
In case of contact with the eyes of the drug, they should be immediately washed with plenty of water or sodium chloride solution. If the drug gets on the skin, it is necessary to immediately wash the place of contact with the drug with a large amount of water. If the drug is inhaled or enters the mouth, seek medical advice immediately.
Influence on the ability to drive a car and other mechanisms.Special studies on the effect of oxaliplatin on the rate of psychomotor reactions have not been conducted. But due to the fact that the use of oxaliplatin can develop nausea, vomiting, dizziness and other neurological symptoms that affect the General condition, from driving and working with other mechanisms for this period it is recommended to refrain.
Storage conditions:
Infusion solution-during the day, at a temperature of 2-8 °C.