Composition, form of production and packaging
Concentrate for the preparation of a solution for infusions is transparent, colorless or almost colorless with a yellowish tinge.
1 ml of 1 fl.
oxaliplatin 5 mg 50 mg
Excipients: lactose monohydrate, water d / u.
10 ml - vials (1) - a film (1) - packs cardboard.
Concentrate for the preparation of a solution for infusions is transparent, colorless or almost colorless with a yellowish tinge.
1 ml of 1 fl.
oxaliplatin 5 mg 100 mg
Excipients: lactose monohydrate, water d / u.
20 ml - vials (1) - a film (1) - packs cardboard.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2011.
PHARMACHOLOGIC EFFECT
An antitumor drug belonging to a new class of compounds based on platinum, in which the 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 tumors resistant to cisplatin. The effect manifests itself regardless of the phase of the cell cycle. When used with fluorouracil synergism of cytotoxic effects is observed. The mechanism of the antitumor effect of oxaliplatin is based on the cytotoxic effect and has not been fully studied. Presumably, oxaliplatin forms inter- and intracerebral 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 second hour after administration at a dose of 130 mg / m 2 , with 15% of platinum introduced in the blood, and the remaining 85% are quickly distributed into tissues or excreted by the kidneys.
Platinum binds to plasma albumin and is excreted in the urine for the first 48 hours. By the fifth day, about 54% of the entire dose is found in the urine and less than 3% in the stool.
Pharmacokinetics in special clinical cases
With renal insufficiency, there is a significant decrease in clearance of oxaliplatin from 17.55 В± 2.18 l / h to 9.95 В± 1.91 l / h. The effect of severe renal failure on the clearance of platinum has not been studied.
INDICATIONS
- adjuvant therapy of colorectal cancer of the III stage (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 / calcium folinate);
- Ovarian cancer (as a second line of therapy).
DOSING MODE
Oxaliplatin-Teva is prescribed only to adults in the form of intravenous infusion for 2-6 hours. Hyperhydration with the use of the drug is not required. If Oxaliplatin-Teva is used in combination with fluorouracil, the oxaliplatin-Teva infusion should precede the administration of fluorouracil.
Adjuvant therapy for colorectal cancer is 85 mg / m 2 once every 2 weeks for 12 cycles (6 months).
Treatment of disseminated colorectal cancer is 85 mg / m 2 once or twice a week as monotherapy or in combination with fluorouracil.
Treatment of ovarian cancer - 85 mg / m 2 1 every 2 weeks as a monotherapy or in combination with other chemotherapeutic drugs.
Repeated administration of Oxaliplatin-Teva is performed only at a neutrophil count of more than 1.5 Г— 10 9 / L and platelets greater than 50 Г— 10 9 / L.
Recommendations for dose adjustment and administration of oxaliplatin
When hematological disorders (the number of neutrophils <1.5 Г— 10 9 / l and / or platelets <50 Г— 10 9 / 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 III - IV degree (number of neutrophils <1-10%), thrombocytopenia of III-IV degree (the amount of platelets is 50-10%), the dose of Oxaliplatin-Teva with subsequent injections should be reduced from 85 mg / m 2to 65 mg / m 2 in the treatment of disseminated colorectal cancer and ovarian cancer; up to 75 mg / m 2 with adjuvant therapy for colorectal cancer in addition to the usual dose reduction of fluorouracil in the case of their combined use.
Patients who, during infusion or within a few hours after a 2-hour infusion, develop acute laryngeal-pharyngeal dysesthesia, the next infusion of oxaliplatin-Teva should be performed within 6 hours.
When pain (as a sign of neurotoxicity) lasts more than 7 days or when paresthesia without functional impairment persists until the next cycle, the subsequent dose of Oxaliplatin-Teva should be reduced by 25%.
With paresthesia with functional impairment, which persists until the next cycle, Oxaliplatin-Teva should be withdrawn; with a decrease in the severity of the symptoms of neurotoxicity after the withdrawal of Oxaliplatin-Teva, the resumption of treatment may be considered.
With the development of stomatitis and / or mucositis II and more toxicity, treatment with Oxaliplatin-Teva should be suspended until they stop or reduce toxicity to the I degree.
Data on the use of oxaliplatin in patients with severe renal impairment are not present. Due to the limited data on safety and tolerability of the drug in patients with moderate renal impairment , the benefit / risk relationship 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 control of kidney function. With a mild degree of impaired renal function, dosage adjustment for oxaliplatin is not required.
Changes in the dosing regimen in patients with mild to moderate liver function impairment are not required. Data on the use of oxaliplatin in patients with severe impairment of liver function are absent.
No dosage adjustment is necessary for the administration of oxaliplatin to elderly patients over the age of 65 (including when used in combination with fluorouracil).
Rules for the preparation and administration of a solution
Do not use needles or other equipment containing aluminum when preparing and administering Oxaliplatin-Teva.
To prepare an infusion solution of oxaliplatin dilute 250-500 ml of a 5% solution of dextrose. The concentration of the resulting solution of oxaliplatin 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 / m 2 .
To prepare the drug solution, only the recommended solvents should be used.
Do not apply the drug undiluted.
0.9% solution of sodium chloride and other saline solutions can not be used to dissolve the drug or dilute the drug solution (for the preparation of the infusion solution).
Do not mix in the same container and prescribe simultaneously in one 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 concomitantly with calcium folinate infusions. In this case, the preparations should not be mixed in the same infusion container.Calcium folinate for infusion should be diluted with a 5% solution of dextrose, but in no case should 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 can not be used.
The solution of the drug is used immediately after preparation.
The drug is intended for single use only. Unused solution of the drug should be destroyed.
In the case of extravasation, the drug should be discontinued immediately.
SIDE EFFECT
The incidence 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 rarely (? 1/10 000), including individual messages.
From the hemopoietic system: very often - anemia, leukopenia, neutropenia, thrombocytopenia, lymphopenia; often - febrile neutropenia (including grade 3-4), sepsis against neutropenia; rarely - hemolytic anemia, immune thrombocytopenia.
On the part of 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 portal blood flow, liver pelitis, nodular regenerative hyperplasia of the hepatic tissue, perisinusoidal fibrosis; Clinically complications are manifested by portal hypertension and / or increased activity of hepatic transaminases.
From the side of the nervous system: very often - peripheral sensory neuropathy, sensitivity disorders, headache, asthenia; often - dizziness, meningism, depression, insomnia; infrequent - 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 docked in the interval between courses, increases depending on the total dose of oxaliplatin.Functional disorders in the form of difficulty in performing accurate movements are possible consequences of sensory damage. The risk of functional disorders at a total dose of about 850 mg / m 2 (10 cycles) is about 10%, reaching 20% ​​in the case of a total dose of 1020 mg / m 2 (12 cycles). After cessation of treatment in most cases, the severity of neurologic symptoms decreases or they completely stop. In 3% of patients 3 years after the end of treatment, either stable local paresthesias of moderate intensity (2.3%) or paresthesia affecting functional activity (0.5%) were observed. On the background of treatment with oxaliplatin, acute neurosensory manifestations were noted, 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 hypoesthesia, rarely (1-2%) - an acute syndrome of laryngeal pharyngeal dysesthesia. The latter manifested itself as a subjective feeling of dysphagia and dyspnea without objective signs of respiratory distress syndrome (cyanosis or hypoxia), or spasm of the larynx, or bronchospasm (without stridor or wheezing). Also observed were 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 both without the use of drug therapy, and with the administration of antihistamines and bronchodilators. Increasing the duration of infusion in subsequent cycles of oxaliplatin therapy can reduce the incidence of this syndrome.
From the musculoskeletal system: very often - pain in the back; often - arthralgia, pain in the bones.
From the respiratory system: very often - cough, shortness of breath; often - rhinitis, infections of the upper respiratory tract, pain in the chest area; rarely - interstitial pneumonia, pulmonary fibrosis.
From the cardiovascular system: often - chest pain, thrombophlebitis of deep veins, thromboembolism of pulmonary arteries.
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 from the nails.
On the part of the organs of sight and hearing: often - conjunctivitis, visual impairment; rarely - transient reduction in visual acuity, loss of visual fields, optic neuritis, decreased hearing, neuritis of the auditory nerve.
Allergic reactions: rarely (when used as monotherapy) or often (in combination with fluorouracil and calcium folinate), bronchospasm, angioedema, lowering of blood pressure, anaphylactic shock can occur. Often there have been cases of allergic manifestations, such as a rash (especially hives), conjunctivitis or rhinitis.
Local reactions: with extravasation of the drug - redness, pain and inflammatory reactions at the injection site.
From the laboratory indicators: very often - hypokalemia, hyponatremia, hyperglycemia, increased alkaline phosphatase, liver enzymes, bilirubin, lactate dehydrogenase; often - increasing the level of creatinine.
Other: very often - fever, increased fatigue, weight gain, taste disorders, nosebleeds.
CONTRAINDICATIONS
- Myelosuppression before the first course of therapy with a neutrophil level less than 2 Г— 10 9 / L and / or platelets less than 100 Г— 10 9 / L;
- peripheral sensory neuropathy with functional disorders before the start of the first course of therapy;
- pronounced impairment of kidney function (QC less than 30 ml / min);
- Pregnancy;
- the period of lactation (breastfeeding);
- childhood;
- hypersensitivity to oxaliplatinum, other derivatives of platinum or other components of the drug.
FROM Caution should be given to the drug for violations of kidney function, severe violations of liver function.
PREGNANCY AND LACTATION
Contraindicated the use of the drug during pregnancy and lactation.
Women and men of childbearing age during treatment with Oxaliplatin-Teva and within 6 months after the end of Oxaliplatin-Teva therapy should use reliable methods of contraception.
APPLICATION FOR FUNCTIONS OF THE LIVER
Data on the use of oxaliplatin in patients with severe renal impairment are not present. Due to the limited data on safety and tolerability of the drug in patients with moderate renal impairment, the benefit / risk relationship 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 control of kidney function. With a mild degree of impaired renal function, dosage adjustment for oxaliplatin is not required.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
Changes in the dosing regimen in patients with mild to moderate liver function impairment are not required. Data on the use of oxaliplatin in patients with severe impairment of liver function are absent.
APPLICATION FOR CHILDREN
Contraindicated: children's age.
APPLICATION IN ELDERLY PATIENTS
No dosage adjustment is necessary for the administration of oxaliplatin to elderly patients over the age of 65 (including when used in combination with fluorouracil).
SPECIAL INSTRUCTIONS
Oxaliplatin-Teva should be used only under the supervision of an oncologist who has experience with antitumor drugs.
Regularly (once a week), as well as before each injection of the drug, it is necessary to monitor the peripheral blood elements and the renal and hepatic function.
Before the beginning of each treatment and during treatment, a neurological examination of patients should be performed to identify signs of neurotoxicity, especially when 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 preserving the symptoms of peripheral sensory neuropathy after the end of the course of treatment. Localized mild paresthesias with functional disorders can persist up to 3 years after the end of the drug for adjuvant therapy.
If respiratory symptoms (dry cough, dyspnoea, wheezing, or pulmonary infiltrates are detected during X-ray examination), treatment with Oxaliplatin-Teva should be stopped until the presence of interstitial pneumonitis is excluded.
Symptoms such as dehydration, paralytic ileus, intestinal obstruction, hypokalemia, metabolic acidosis and kidney 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 the anamnesis should be monitored for allergic symptoms. In case of reaction to oxaliplatin-Teva, similar to anaphylactic, infusion should be immediately interrupted and appropriate symptomatic treatment should be prescribed. Further use of Oxaliplatin-Teva in the case of allergic reactions is contraindicated.
In the case of extravasation, the infusion should be stopped immediately and local symptomatic treatment started. The remaining dose of the drug should be injected into another vein.
If the product gets into the eyes, they must be washed immediately with a large amount of water or a solution of sodium chloride. In case of contact with the skin, immediately contact the product with plenty of water. If the product is inhaled or if it gets into the mouth, immediately consult a doctor.
Impact on the ability to drive vehicles and manage mechanisms
Special studies on the effect of oxaliplatin on the rate of psychomotor reactions have not been conducted. But since nausea, vomiting, dizziness and other neurological symptoms that affect the general condition, from driving the car and working with other mechanisms during this period, it is recommended to abstain from using oxaliplatin.
OVERDOSE
Symptoms: myelosuppression, neurotoxicity, diarrhea, nausea, vomiting.
Treatment: hematology control and symptomatic therapy. The antidote to oxaliplatin is not known.
DRUG INTERACTION
Significant changes oxaliplatin binding to plasma proteins, while the use erythromycin, salicylates, granisetron, paclitaxel and valproic acid was not observed.
By reaction with aluminum may precipitate and decrease the activity of oxaliplatin.
Oxaliplatin pharmaceutically-Teva is not compatible with 0.9% sodium chloride and other sodium solutions containing chlorine, as well as alkaline solutions.
TERMS OF RELEASE FROM PHARMACY
The drug is released by prescription.
TERMS AND CONDITIONS OF STORAGE
List B. The drug should be stored in a place protected from light, inaccessible to children at a temperature of no higher than 25 В° C. Shelf life - 2 years.
