Oxaliplatin concentrate solution for infusions 5mg/ml 20ml

Concentrate for solution for infusion.

Packaging

In a bottle of 20 ml of concentrate. In carton packaging 1 bottle.

Mechanism of action

Pharmacodynamics

An anticancer drug, which belongs to a new class of platinum-based compounds, in which a platinum atom forms a complex bond with 1,2-diaminocyclohexane (DACG) and an oxalate group.

Oxaliplatin has antitumor activity in various types of tumors, including colorectal cancer. It is also effective in the treatment of Cisplatin resistant tumors. The action manifests itself regardless of the phase of the cell cycle. When used with Fluorouracil, synergism of cytotoxic action is observed. The mechanism of the antitumor effect of oxaliplatin is based on the cytotoxic effect and is not fully understood. Presumably, oxaliplatin forms inter-and intracellular bonds with DNA, thereby inhibiting the phases of its replication and transcription.

Pharmacokinetics

In vivo oxaliplatin undergoes active biotransformation and is not detected in the plasma by the end of the 2nd hour after administration at a dose of 130 mg / m², while 15% of the injected platinum is in the blood, and the remaining 85% is quickly distributed to the tissues or excreted by the kidneys.

Platinum is bound to plasma albumin and excreted in the urine during the first 48 hours. By the 5th day, about 54% of the total dose is found in the urine and less than 3% in the feces.

Pharmacokinetics in special clinical situations

In renal failure, a significant decrease in oxaliplatin clearance is observed from 17.55 &№177; 2.18 l / h to 9.95 &№177; 1.91 l / h. The effect of severe renal failure on platinum clearance has not been studied.

Indications and usage

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

Contraindications

• Myelosuppression before the first course of therapy with a neutrophil level of less than 2 &№215; 10⁹/ l and / or platelets less than 100 &№215; 10⁹/ l;
• peripheral sensory neuropathy with functional disorders prior to the first course of therapy;
• marked impaired renal function (CC less than 30 ml / min);
• pregnancy;
• lactation period (breastfeeding);
• childhood;
• Hypersensitivity to oxaliplatin, other platinum derivatives or other components of the drug.

Carefully: It should appoint a drug for violations of the kidneys, severe violations of the liver.

Pregnancy and Breastfeeding

The drug is contraindicated during pregnancy and lactation.

Women and men of childbearing age during treatment with oxaliplatin-teva and for 6 months after the end of therapy with oxaliplatin-teva, reliable methods of contraception should be used.

Oxaliplatin-Teva should be used only under the supervision of an oncologist with experience in working with anticancer drugs.

Regularly (1 time per week), as well as before each administration of the drug, it is necessary to monitor the uniform elements of the peripheral blood and indicators of kidney and liver function.

Before the start of each injection and during the course of treatment, a neurological examination of patients should be carried out to identify signs of neurotoxicity, especially when using Oxaliplatin-Teva with other drugs 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 the course of treatment. Localized moderate paresthesia with functional disorders may persist up to 3 years after the end of the use of the drug in order to adjuvant therapy.

If respiratory symptoms appear (dry cough, dyspnea, wheezing, or pulmonary infiltrates during X-ray examination), treatment with Oxaliplatin-Teva should be suspended until the presence of interstitial pneumonitis is excluded.

Symptoms such as dehydration, paralytic ileus, intestinal obstruction, hypokalemia,metabolic acidosis and renal failure may be due to severe diarrhea or vomiting, especially when using Oxaliplatin-Teva in combination with fluorouracil.

Patients with allergic reactions to other platinum compounds in the history should be monitored for the presence of allergic symptoms. In the event of a reaction to Oxaliplatin-Teva, similar to the anaphylactic one, the infusion should be immediately interrupted and appropriate symptomatic treatment should be prescribed. Further use of Oxaliplatin-Teva in the event of the development of allergic reactions is contraindicated.

In case of extravasation, the infusion should be stopped immediately and local symptomatic treatment should begin. The remaining dose of the drug should be injected into another vein.

In case of contact with the eyes, wash them immediately with plenty of water or sodium chloride solution. In case of contact with the skin, immediately rinse the place of contact with the drug with a large amount of water. In the case of inhalation of the drug or getting it into the mouth, you should immediately consult a doctor.

Influence on the ability to drive vehicles and other mechanisms that require high concentration of attention

Special studies on the effect of oxaliplatin on the speed of psychomotor reactions have been conducted. But since With the use of oxaliplatin, nausea, vomiting, dizziness and other neurological symptoms that affect the general condition may develop, it is recommended to refrain from driving a car and working with other mechanisms during this period.

Active ingredient

1 ml (1 bottle) contains:

Active substances: oxaliplatin 5 mg (50 mg).

Excipients: lactose monohydrate, water d / i.

Dosage and administration

Oxaliplatin-Teva is prescribed only for adults in the form of intravenous infusion for 2-6 hours. Hyperhydration is not required when using the drug. If Oxaliplatin-Teva is used in combination with fluorouracil, Oxaliplatin-Teva infusion should be preceded by the introduction 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 in 2 weeks as monotherapy or in combination with fluorouracil.

Ovarian cancer treatment - 85 mg / m² Once in 2 weeks as monotherapy or in combination with other chemotherapeutic drugs.

Repeated administration of oxaliplatin-teva is performed only with neutrophil count more than 1.5 &№215; 10⁹/ l and platelets over 50 &№215; 10⁹/ l.

Recommendations for dose adjustment and regimen of oxaliplatin

In hematological disorders (neutrophil count <1.5 &№215; 10⁹/ l and / or platelet <50 &№215; 10⁹/ l), the next course is postponed until the restoration of normal laboratory parameters.

With the development of diarrhea IV degree of toxicity (according to the WHO scale), neutropenia III-IV degree (neutrophil count <1 &№215; 10%), thrombocytopenia III-IV degree (platelet count 50 &№215; 10%), the dose of Oxaliplatin-Teva should be reduced in subsequent administrations with 85 mg / m² up to 65 mg / m² in the treatment of disseminated colorectal and ovarian cancer; up to 75 mg / m² with adjuvant treatment of colorectal cancer in addition to the usual dose reduction of fluorouracil in the case of their combined use.

For patients who develop acute laryngopharyngeal dysesthesia during an infusion or within a few hours after a 2-hour infusion, the following Oxaliplatin-Teva infusion should be given within 6 hours.

With the appearance of pain (as a sign of neurotoxicity) lasting more than 7 days or with paresthesia without functional impairment that persists until the next cycle, the subsequent dose of Oxaliplatin-Teva should be reduced by 25%.

With paresthesia with functional impairment that lasts until the next cycle, Oxaliplatin-Teva should be canceled; if the severity of symptoms of neurotoxicity is reduced after the withdrawal of Oxaliplatin-Teva, the question of resuming treatment can be considered.

With the development of stomatitis and / or mucositis II and more of a degree of toxicity, treatment with Oxaliplatin-Teva should be suspended until they stop or reduce the manifestations of toxicity to degree I.

Data on the use of oxaliplatin in patients with severe renal impairment not. Due to limited data regarding 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 the careful control of renal function. With a mild degree of renal impairment dose adjustment oxaliplatin is not required.

Changes in dosing regimen in patients with weak or moderate liver dysfunction is not required. There are no data on the use of oxaliplatin in patients with severely impaired liver function.

Correction of the dosing regimen is not required when prescribing oxaliplatin elderly patients over the age of 65 (including when used in combination with fluorouracil).

Rules for the preparation and administration of the solution

When preparing and when administering Oxaliplatin-Teva, needles and other equipment containing aluminum cannot be used.

To prepare an infusion solution, oxaliplatin is diluted with 250-500 ml of a 5% dextrose solution. The concentration of the resulting solution oxaliplatin should be from 0.2 to 0.7 mg / ml; at the same time, 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 should be used only recommended solvents.

Do not use the drug undiluted.

You can not use for dissolving the drug or diluting the solution of the drug (for the preparation of an infusion solution) 0.9% solution of sodium chloride and other salt solutions.

It should not be mixed in the same container and administered simultaneously in the same infusion system with other drugs (especially with fluorouracil, trometamol, and folinate calcium preparations containing trometamol in its composition), alkaline solutions or solutions containing chlorides.

Oxaliplatin may be administered together with folinate calcium infusions. In this case, the drugs should not be mixed in a single container for infusion. Calcium folinate for infusion should be diluted with a 5% dextrose solution, but in no case should you use solutions containing sodium chloride or alkaline solutions.

The prepared solution of the drug should be transparent and should not contain undissolved particles. Otherwise, the drug solution can not be used.

A solution of the drug is used immediately after preparation.

The drug is intended for single use only.Unused solution of the drug must be destroyed.

In case of extravasation, the drug should be immediately discontinued.

The frequency of adverse reactions below was determined according to the following criteria:

• very often (> 1/10);
• often (> 1/100, ≤1 / 10);
• infrequently (> 1/1000, ≤ 1/100);
• rarely (> 1/10 000, ≤1 / 1000);
• very rarely (≤1 / 10,000), including individual messages.

From the hemopoietic system: very often - anemia, leukopenia, neutropenia, thrombocytopenia, lymphopenia; often - febrile neutropenia (including 3-4 degrees), sepsis on 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, gastroesophageal reflux, intestinal bleeding, hiccups, metabolic acidosis, pancreatitis; infrequently - paralytic ileus, intestinal obstruction; rarely colitis, including cases of pseudomembranous colitis.

From the hepatobiliary system: very rarely, sinusoidal obstruction of the portal blood flow, liver paliosis, nodular regenerative hyperplasia of the liver 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 usually stop in the interval between courses, increases depending on the total dose of oxaliplatin. Functional impairments in the form of difficulty in performing precise movements are possible consequences of sensory damage. The risk of functional impairment 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 cessation of treatment in most cases, the severity of neurological symptoms diminishes or they stop completely. In 3% of patients after 3 years after the end of treatment, either sustained local paresthesias of moderate intensity (2.3%) or paresthesias affecting the functional activity (0.5%) were observed.Acne neurosensory manifestations were noted during treatment with oxaliplatin, which usually occurred within a few hours after the administration of the drug and were most often provoked by exposure to cold. They were characterized by transient paresthesia, dysesthesia or hypesthesia, rarely (1-2%) - acute syndrome of laryngopharyngeal dysesthesia. 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 spasm of the larynx, or bronchospasm (without stridor or wheezing). Also observed were phenomena such as muscle spasm of the jaw, tongue dysesthesia, dysarthria and pressure sensation in the chest. Typically, these symptoms were quickly relieved as without the use of drug therapy, and with the introduction of antihistamines and bronchodilators. Increasing the duration of infusion in subsequent cycles of oxaliplatin therapy can reduce the frequency of this syndrome.

From the musculoskeletal system: very often - back pain; often - arthralgia, bone pain.

On the part of the respiratory system: very often - cough, shortness of breath; often - rhinitis, upper respiratory tract infections, pain in the chest; rarely - interstitial pneumonia, pulmonary fibrosis.

Since the cardiovascular system: often - chest pain, deep vein thrombophlebitis, pulmonary thromboembolism.

From the urinary system: often - hematuria, dysuria, hemolytic-uremic syndrome, acute tubular necrosis, acute interstitial nephritis, acute renal failure .

Dermatological reactions: very often - alopecia, skin rashes; often - peeling of the skin of the palms and feet, erythematous rashes, excessive sweating, changes in the nails.

From the organs of sight and hearing: often - conjunctivitis, visual disturbances; rarely, transient reduction of visual acuity, loss of visual fields, optic neuritis, hearing loss, acoustic neuritis.

Allergic reactions: rarely (when used as monotherapy) or often (in combination with fluorouracil and calcium folinate) bronchospasm, angioedema, decrease in blood pressure, anaphylactic shock can be observed.Often there have been cases of such allergic manifestations as a rash (especially urticaria), conjunctivitis, or rhinitis.

Local reactions: with the extravasation of the drug - redness, pain and inflammatory reactions at the injection site.

From the laboratory indicators: very often - hypokalemia, hyponatremia, hyperglycemia, increased levels of alkaline phosphatase, liver enzyme activity, bilirubin content, lactate dehydrogenase; often - increased creatinine levels.

Other: very often - an increase in body temperature, increased fatigue, increase in body weight, taste disturbances, nosebleeds.

Significant changes in the binding of oxaliplatin to plasma proteins with simultaneous use with Erythromycin, salicylates, granisetron, Paclitaxel and valproic acid were not observed.

When interacting with aluminum, the formation of a precipitate and a decrease in the activity of oxaliplatin are possible.

Oxaliplatin-Teva is not pharmaceutically compatible with 0.9% sodium chloride solution and other solutions containing chlorides, as well as alkaline solutions.

Symptoms: myelosuppression, neurotoxicity, diarrhea, nausea, vomiting.

Treatment: hematological control and symptomatic therapy. Antidote to oxaliplatin is not known.

To store in protected from light, the place, inaccessible for children, at a temperature not above 25 ° C.