Oxaliplatin-Teva concentrate for infusion solution 5mg/ml 10ml vial, 1pc

Composition

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1 ml (1 bottle) contains:

Active ingredients:

oxaliplatin 5 mg (100 mg).

Auxiliary substances:

lactose monohydrate,

d/i water.

The bottle contains 20 ml of concentrate.

In a cardboard box 1 bottle.

Pharmacological action

Pharmacodynamics

antitumor drug belonging to a new class of platinum-based compounds, in which a platinum atom forms a complex bond with 1,2-diaminocyclohexane (DAC) 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 effect is manifested regardless of the phase of the cell cycle. When used with fluorouracil, a synergistic cytotoxic effect is observed. The mechanism of the antitumor effect of oxaliplatin is based on cytotoxic action and is not fully understood. Presumably, oxaliplatin forms inter-and inter-stranded bonds with DNA, thereby inhibiting the phases of its replication and transcription.

Pharmacokinetics

In vivo oxaliplatin undergoes active biotransformation and is not detected in plasma by the end of 2 hours after use at a dose of 130 mg / m2, while 15% of the administered platinum is in the blood, and the remaining 85% is rapidly 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 detected in the urine and less than 3% in the feces.

Pharmacokinetics in special clinical cases

In patients with renal insufficiency, there is a significant decrease in the clearance of oxaliplatin from 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.

Indications

• Adjuvant therapy for stage III colorectal cancer (Duke C) 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).

Use during pregnancy and lactation

The drug is contraindicated during pregnancy and lactation.

Women and men of childbearing age should use reliable methods of contraception during treatment with Oxaliplatin-Teva and for 6 months after the end of Oxaliplatin-Teva therapy.

Contraindications

• Myelosuppression prior to 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 impairment prior to first course of therapy;
• marked impairment of renal function (QC less than 30 ml/min);
• pregnancy;
• lactation (breastfeeding);
• child;
• hypersensitivity to oxaliplatin, other derivatives of platinum or other components of the drug.

With caution: the drug should be prescribed for impaired renal function, severe liver function disorders.

Side effects

The frequency of adverse reactions listed 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 rare (less than 1/10,000), including individual messages.

From the hematopoietic system: very often – anemia, leukopenia, neutropenia, thrombocytopenia, lymphopenia; often-febrile neutropenia (including grade 3-4), 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 side of the hepatobiliary system: very rarely sinusoidal obstruction of portal blood flow, liver peliosis, 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, the symptoms of sensory neuropathy are provoked by cold. The duration of these symptoms, which are usually relieved between courses, increases depending on the total dose of oxaliplatin. Functional disorders in the form of difficulty 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 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 paresthesias of moderate intensity (2.3%) or paresthesias affecting functional activity (0.5%) were observed. Against the background of oxaliplatin treatment, acute sensorineural manifestations were noted, which usually occurred within a few hours after use 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 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 laryngeal spasm, or bronchospasm (without stridor or wheezing). There were also symptoms such as jaw muscle spasms, tongue dysesthesia, dysarthria, and chest pressure. Usually, these symptoms were quickly relieved both without the use of medication, and with the introduction of antihistamines and bronchodilators. Increasing the duration of the infusion during subsequent cycles of oxaliplatin therapy reduces the frequency 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, chest pain; rarely – interstitial pneumonia, pulmonary fibrosis.

From the cardiovascular system: often-pain behind the sternum, deep vein thrombophlebitis, pulmonary embolism.

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, increased sweating, changes in the nails.

From the side of the organs of vision and hearing: often-conjunctivitis, visual disturbances; rarely-transient decrease in visual acuity, loss of visual fields, neuritis of the optic nerve, hearing loss, neuritis of the auditory nerve.

Allergic reactions: rarely (when used as monotherapy) or often (in combination with fluorouracil and calcium folinate), bronchospasm, angioedema, decreased blood pressure, anaphylactic shock may occur. Allergic reactions such as rash (especially urticaria), conjunctivitis or rhinitis were frequently reported.

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

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

Other: very often-increased body temperature, increased fatigue, weight gain, taste disorders, nosebleeds.

Interaction

No significant changes in the binding of oxaliplatin to plasma proteins were observed when co-administered with erythromycin, salicylates, granisetron, paclitaxel, and valproic acid.

When interacting with aluminum, it is possible to form a precipitate and reduce the activity of oxaliplatin.

Oxaliplatin-Teva is pharmacologically incompatible with 0.9% sodium chloride solution and other solutions containing chlorides, as well as alkaline solutions.

How to take it, course of use and dosage

Oxaliplatin-Teva is prescribed only for adults as an intravenous infusion for 2-6 hours. Hyperhydration is not required when using the drug. If Oxaliplatin-Teva is used in combination with fluorouracil, the Oxaliplatin-Teva infusion should precede the use of fluorouracil.

Adjuvant therapy of 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 chemotherapeutic drugs.

Repeated use of Oxaliplatin-Teva is performed only when the number of neutrophils exceeds 1.5×109/l and platelets exceeds 50×109/l.

Recommendations for adjusting the dose and mode of use of oxaliplatin

With hematological disorders (neutrophil count < 1.5×109/l and / or platelets

With the development of diarrhea of the IV degree of toxicity (according to the WHO scale), neutropenia of the III-IV degree (neutrophil count

Patients who develop acute laryngopharyngeal dysesthesia during the infusion or within a few hours after the 2-hour infusion, the next infusion of Oxaliplatin-Teva should be performed within 6 hours.

If there is pain (as a sign of neurotoxicity) lasting more than 7 days or if paresthesia without functional disorders persists until the next cycle, the subsequent dose of Oxaliplatin-Teva should be reduced by 25%.

If paresthesia with functional disorders persists until the next cycle, Oxaliplatin-Teva should be discontinued; if the severity of neurotoxicity symptoms decreases after discontinuation of Oxaliplatin-Teva, you can consider resuming treatment.

With the development of stomatitis and / or mucositis of the second and higher degree of toxicity, treatment with Oxaliplatin-Teva should be suspended until they stop or reduce the manifestations of toxicity to the first degree.

There are no data on the use of oxaliplatin in patients with severe renal impairment. Due to limited data on 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. In patients with mild renal impairment, no dose adjustment of oxaliplatin is required.

Changes in the dosage regimen in patients with mild or moderate hepatic impairment are not required. There are no data on the use of oxaliplatin in patients with severe hepatic impairment.

There is no need to adjust the dosage regimen when prescribing oxaliplatin to elderly patients over the age of 65 years (including when used in combination with fluorouracil).

Rules for preparation and use of the solution

When preparing and administering Oxaliplatin-Teva, 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, with 0.7 mg / ml being the highest concentration used in clinical practice at a dose of 85 mg / m2.

Only the recommended solvents should be used to prepare the drug solution.

Do not use the drug 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).

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 calcium folinate preparations containing trometamol in their composition), alkaline solutions or solutions containing chlorides.

Oxaliplatin may be administered 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 solution of the drug can not be used.

The solution of the drug is used immediately after preparation.

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

In case of extravasation, the drug use should be stopped immediately.

Overdose

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

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

Special instructions

Oxaliplatin-Teva should only be used under the supervision of an oncologist who has experience with antitumor drugs.

Regularly (once a week), as well as before each use of the drug, it is necessary to monitor the formed elements of peripheral blood and indicators of kidney and liver function.

Before starting each use and during treatment, patients should be neurologically examined for signs of neurotoxicity, especially if Oxaliplatin-Teva is used with other drugs that have a specific toxic effect on the nervous system. Patients should be informed about the possibility of maintaining symptoms of peripheral sensory neuropathy after the end of the course of treatment. Localized moderate paresthesias with functional impairments may persist for up to 3 years after the end of adjuvant therapy.

If respiratory symptoms appear (dry cough, dyspnoea, wheezing, or detection of 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 Oxaliplatin-Teva is used in combination with fluorouracil.

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

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

If the drug gets into the eyes, they should be immediately rinsed 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, consult a doctor immediately.

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

Special studies on the effect of oxaliplatin on the speed of psychomotor reactions have not been conducted. However, since the use of oxaliplatin may cause nausea, vomiting, dizziness and other neurological symptoms that affect the general condition, it is recommended to refrain from driving a car and working with other mechanisms for this period.

Form of production

Concentrate for preparation of solution for infusions

Storage conditions

Store in a place protected from light and out of reach of children at a temperature not exceeding 25°C.

Shelf

life is 2 years.

Active ingredient

Oxaliplatin

Conditions of release from pharmacies

By prescription

Dosage form

infusion solution