oxaliplatin | Oxaliplatin-Teva conc. for solution for infusions 5 mg / ml 40 ml bottle 1 pc.

Latin name

OXALIPLATIN-TEVA

Release form

Concentrate for solution for infusion.

Packaging

In a bottle of 10 ml of concentrate. In a cardboard box 1 bottle.

Pharmacological action

Pharmacodynamics

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 (DACG) and the 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 is manifested regardless of the phase of the cell cycle. When used with fluorouracil, a synergism of the cytotoxic effect 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 intra-linkages with DNA, thereby inhibiting the phases of its replication and transcription.

Pharmacokinetics of

In vivo, oxaliplatin undergoes active biotransformation and is not detected in plasma by the end of the 2nd hour after administration 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 during the first 48 hours. By the 5th day, about 54% of the entire dose is found in urine and less than 3% in feces.

Pharmacokinetics in special clinical cases

With renal failure, a significant decrease in oxaliplatin clearance is observed 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 (C according to 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 sperm / calcium cancer as a second line of therapy).

Contraindications

Myelosuppression before the start of the first course of therapy at a neutrophil level of less than 2 × 109 / L and / or platelets less than 100 × 109 / L

peripheral sensory neuropathy with functional impairment before the first course of therapy

pronounced impaired renal function (K ml / min)

pregnancy

lactation (breastfeeding)

children

hypersensitivity to oxaliplatin, other platinum derivatives or other components of the drug.

Caution: the drug should be prescribed for impaired renal function, severe impaired liver function.

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 within 6 months after the end of therapy with oxaliplatin-teva.

Composition

1 ml (1 vial) contains:

Active substances: oxaliplatin 5 mg (50 mg).

Excipients: lactose monohydrate, water d / and.

Dosage and administration of

Oxaliplatin-Teva is prescribed only for adults in the form of iv 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 be preceded by 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 every 2 weeks as a monotherapy or in combination with fluorouracil.

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

Repeated injections of Oxaliplatin-Teva are performed only when the number of neutrophils exceeds 1.5 × 109 / L and platelets exceeds 50 × 109 / L.

Recommendations for dose and regimen administration of oxaliplatin

In case of hematologic abnormalities (neutrophils <1.5 × 109 / L and / or platelets <50 × 109 / L), the next course is postponed until normal laboratory parameters are restored.

With the development of diarrhea of ​​the IV degree of toxicity (according to the WHO scale), neutropenia of the III-IV degree (the number of neutrophils <1 × 10%), thrombocytopenia of the III-IV degree (platelet count 50 × 10%), the dose of Oxaliplatin-Teva should be reduced from 85 mg / m2 to 65 mg / m2 for the treatment of disseminated colorectal cancer and ovarian cancer to 75 mg / m2 for adjuvant colorectal therapy cancer in addition to the usual dose reduction of fluorouracil in case of their combined use.

In patients who develop acute laryngeal pharyngeal dysesthesia during the infusion or within a few hours after the 2-hour infusion, the next infusion of Oxaliplatin-Teva should be carried out for 6 hours.

If pain (as a sign of neurotoxicity) lasts longer than 7 days or with paresthesia without functional impairment, which persists until the next cycle, the subsequent dose of Oxaliplatin-Teva should be reduced by 25%.

In case of paresthesia with functional impairment that persists until the next cycle, Oxaliplatin-Teva should be abolished with a decrease in the severity of symptoms of neurotoxicity after the withdrawal of Oxaliplatin-Teva, you can consider resuming treatment.

With the development of stomatitis and / or mucositis of II and more toxicity, treatment with Oxaliplatin-Teva should be suspended until they are stopped or symptoms of toxicity are reduced to I degree.

There are no data on the use of oxaliplatin in patients with severe renal impairment. Due to the limited data on the safety and tolerability of the drug in patients with a moderate degree of impaired renal function, 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 close monitoring of renal function. With a mild degree of renal impairment, dose adjustment of oxaliplatin is not required.

Dosage regimen changes in patients with mild or moderate hepatic impairment are not required. There are no data on the use of oxaliplatin in patients with severely impaired liver function.

Dosage regimen adjustment is not required when prescribing oxaliplatin to elderly patients over 65 years of age (including when used in combination with fluorouracil).

Rules for the preparation and administration of

solution During the preparation and administration of Oxaliplatin-Teva, do not use needles and other equipment containing aluminum.

To prepare the 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, while 0.7 mg / ml is the highest concentration used in clinical practice at a dose of 85 mg / m2.

Only recommended solvents should be used to prepare the 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 (for preparing an infusion solution).

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

Oxaliplatin may be given in conjunction with calcium folinate infusions. In this case, the drugs should not be mixed in the same 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 preparation should be transparent and should not contain undissolved particles. Otherwise, the drug solution should 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 administration of the drug should be stopped immediately.

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)

is very rare ( 1/10 000), including single messages.

From the hemopoietic system: very often - anemia, leukopenia, neutropenia, thrombocytopenia, lymphopenia often - febrile neutropenia (including grade 3-4), sepsis with 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, obstruction rarely - pricks, including cases of pseudomembranous colitis.

From the hepatobiliary system: very rarely, sinusoidal obstruction of the portal blood flow, liver peliosis, nodular regenerative hyperplasia of the liver tissue, perisinusoidal fibrosis, clinical complications are manifested by portal hypertension and / or increased activity of hepatic transaminases.

From the nervous system: very often - peripheral sensory neuropathy, sensory disturbances, headache, asthenia often - dizziness, meningism, depression, insomnia infrequently - increased nervousness rarely - dysarthria, cramps. Neurotoxicity is a dose-limiting factor. Often, symptoms of sensory neuropathy are triggered by a cold. The duration of these symptoms, which usually stop between courses, increases depending on the total dose of oxaliplatin. Functional disturbances in the form of difficulty in performing precise movements are possible consequences of sensory damage. The risk of functional impairment with 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 completely stop. 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%) was observed. Acute sensory manifestations were noted during treatment with oxaliplatin. which usually occurred within a few hours after administration of the drug and most often provoked by exposure to cold. They were characterized by transient paresthesia, dysesthesia or hypesthesia, rarely (1-2%) - acute laryngeal pharyngeal 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). Also observed were spasm of the jaw muscles, tongue dysesthesia, dysarthria and a feeling of pressure in the chest. Typically, these symptoms quickly stopped both without the use of drug therapy, and with the introduction of antihistamines and bronchodilators. An increase in the duration of infusion during subsequent cycles of oxaliplatin therapy can reduce 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, pain in the chest area rarely - interstitial pneumonia, pulmonary fibrosis.

From the cardiovascular system: often - pain behind the sternum, 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 hands and feet, erythematous rashes, excessive sweating, changes in the nails.

On the part of the organs of vision and hearing: often - conjunctivitis, visual impairment rarely - a transient decrease 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) bronchospasm, angioedema, decreased blood pressure, anaphylactic shock can be observed. Often there have been cases of allergic manifestations such as a rash (especially urticaria), conjunctivitis or rhinitis.

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

On the part of laboratory indicators: very often - hypokalemia, hyponatremia, hyperglycemia, increased levels of alkaline phosphatase, liver enzymes, bilirubin, lactate dehydrogenase, often - increased creatinine.

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

No drug interaction of

There was no significant change in the binding of oxaliplatin to blood plasma proteins when co-administered with erythromycin, salicylates, granisetron, paclitaxel, and valproic acid.

Sedimentation and reduction of oxaliplatin activity may occur upon interaction with aluminum.

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

Overdose

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

Treatment: Hematologic control and symptomatic therapy. The antidote to oxaliplatin is unknown.

Storage conditions

Store in a dark place, out of the reach of children, at a temperature not exceeding 25 РC.

Expiration

2 years.

Terms of delivery from pharmacies

Prescription

dosage form

dosage form

infusion solution