Eloxatin
Eloxatin: instructions for use and reviews
- 1. Release form and composition
- 2. Pharmacological properties
- 3. Indications for use
- 4. Contraindications
- 5. Method of application and dosage
- 6. Side effects
- 7. Overdose
- 8. Special instructions
- 9. Application during pregnancy and lactation
- 10. Use in childhood
- 11. In case of impaired renal function
- 12. For violations of liver function
- 13. Use in the elderly
- 14. Drug interactions
- 15. Analogs
- 16. Terms and conditions of storage
- 17. Terms of dispensing from pharmacies
- 18. Reviews
- 19. Price in pharmacies
Latin name: Eloxatin
ATX code: L01XA03
Active ingredient: oxaliplatin (Oxaliplatin)
Manufacturer: Sanofi-Aventis Deutschland, GmbH (Germany); Aventis Pharma (Dagenham) (UK)
Description and photo updated: 2018-29-11
Prices in pharmacies: from 8600 rubles.
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Eloxatin is an antineoplastic agent.
Release form and composition
Dosage form - concentrate for preparation of solution for infusion: transparent, colorless solution (10, 20 or 40 ml in a colorless glass bottle, 1 bottle in a blister contour packaging, 1 package in a cardboard box and instructions for use of Eloxatin).
Composition of 1 ml solution:
- active substance: oxaliplatin - 5 ml;
- auxiliary component: water for injection.
Pharmacological properties
Pharmacodynamics
The active ingredient of Eloxatin, oxaliplatin, is an alkylating compound belonging to a new class of platinum derivatives, in which the platinum atom forms a complex with oxalate and 1,2-diaminocyclohexane.
The drug has a wide range of cytotoxic efficacy. Also in vitro and in vivo is active in various tumor models resistant to cisplatin. When used in combination with fluorouracil, a synergistic cytotoxic effect is noted.
The results of studies of the mechanism of action confirm the hypothesis that biotransformed aqueous derivatives of oxaliplatin, interacting with DNA through the formation of inter- and intra-stranded bridges, suppress DNA synthesis, as a result of which cytotoxic and antitumor effects develop.
Pharmacokinetics
In vivo, oxaliplatin is actively biotransformed. When a dose of 85 mg / m 2 is administered by the end of a 2-hour infusion, no plasma is detected. Approximately 15% of the administered drug is present in the blood, 85% is quickly distributed to tissues.
The substance binds to blood plasma albumin, is excreted by the kidneys within 48 hours.
By the 5th day, about 54% of the entire dose of the drug is found in urine, less than 3% in feces.
It has been reliably established that the excretion of oxaliplatin depends on creatinine clearance (CC). Compared with CC> 80 ml / min, the total plasma clearance for ultrafiltered (in the form of a mixture of all unbound, active / inactive compounds) platinum with CC 50-80 ml / min decreases by 34%, CC 30-49 ml / min - by 57%, with CC <30 ml / min - by 79%. In patients with reduced renal function, the renal clearance of platinum ultrafiltrate in plasma also decreases, therefore, the excretion of the drug by the kidneys decreases.
Indications for use
- disseminated colorectal cancer (in combination with fluorouracil / calcium folinate);
- ovarian cancer (as a second-line drug);
- adjuvant therapy for stage III colon cancer (Duke's stage C) after radical resection of the primary tumor (in combination with fluorouracil / calcium folinate).
Contraindications
- peripheral sensory neuropathy, accompanied by functional disorders, detected before the start of the first course of treatment;
- myelosuppression (neutrophil count <2000 / μl and / or platelets <100,000 / μl) before the start of the first course of therapy;
- age up to 18 years;
- period of pregnancy and lactation;
- hypersensitivity to any component of the drug or other platinum derivatives.
Eloxatin should be used with caution in severe renal impairment (CC <30 ml / min).
Eloxatin, instructions for use: method and dosage
Eloxatin is administered intravenously (IV). Infusion of the drug always precedes the administration of fluorouracil.
Oxaliplatin is injected through the infusion system into peripheral veins or through a central venous catheter simultaneously with intravenous infusion of calcium folinate in 5% dextrose solution for 2-6 hours. To do this, use a Y-shaped system for intravenous administration, connect it immediately before the place of introduction.
Do not mix oxaliplatin and calcium folinate in the same infusion bottle. Calcium folinate should not contain trometamol as an auxiliary component. It can only be diluted with a 5% dextrose solution. For dilution, do not use alkaline solutions, sodium chloride solutions and chloride-containing solutions.
Eloxatin should not be mixed in the same infusion set with any other drugs.
If the drug accidentally gets into the tissues surrounding the vein, the infusion should be stopped immediately and the usual local symptomatic therapy should be started.
During the period of oxaliplatin use, overhydration is not required.
Repeated infusions of Eloxatin are performed only if the number of neutrophils is> 1500 / μl, platelets -> 75,000 / μl.
Recommended dosage regimens of Eloxatin, depending on the indications:
- disseminated colorectal cancer: 85 mg / m 2 once every 2 weeks in combination with fluorouracil and calcium folinate. Treatment is carried out until disease progression or unacceptable toxicity develops;
- ovarian cancer: 85 mg / m 2 once every 2 weeks as a monotherapy or in combination with other chemotherapeutic agents;
- adjuvant therapy for colon cancer: 85 mg / m 2 once every 2 weeks in combination with fluorouracil and calcium folinate. Course - 12 cycles (6 months).
The dosage regimens of fluorouracil and calcium folinate are determined by the doctor, in accordance with their instructions for use.
The dose of Eloxatin can be adjusted depending on the tolerability of the therapy.
If before the start of the first course of treatment or after the end of the drug use, hematological disorders are detected (the number of neutrophils - <1500 / μl and / or platelets - <75,000 / μl), the beginning of the first course or the appointment of the next one is postponed until the number of blood cells is restored to satisfactory values (the number of neutrophils - ≥ 1500 / μl and / or platelets - ≥ 75,000 / μl). Before starting therapy with the drug and before each new cycle, a general blood test is shown, including an accurate determination of the number of platelets and leukocytes.
In the case of severe life-threatening diarrhea, severe thrombocytopenia (platelet count - <50,000 / μl) or severe neutropenia (neutrophil count - <1000 / μl), Eloxatin administration is stopped until the condition / indicators recover / improve. With subsequent injections, the dose of oxaliplatin is reduced by 25%, if necessary, the dose of fluorouracil is also reduced.
With the development of neurological symptoms (manifestations of peripheral sensory neuropathy - paresthesia, dysesthesia), depending on their severity and duration, the dose is adjusted or Eloxatin is canceled. If neurological symptoms bother the patient for more than 7 days, or paresthesias without functional impairment persist until the next cycle of therapy, the subsequent dose of oxaliplatin is reduced by 25%. In cases where paresthesias with functional impairments persist until the beginning of the next cycle, Eloxatin is canceled. After a decrease in the severity of neurological symptoms, the advisability of resuming treatment is considered by the doctor.
There is no need to adjust the dose of Eloxatin in patients with normal / moderate renal impairment. In severe renal impairment, the initial dose of oxaliplatin is reduced to 65 mg / m 2.
Rules for the preparation and use of the infusion solution
For preparation and administration of the solution, do not use needles and any equipment containing aluminum.
To dilute the concentrate, do not use a 0.9% sodium chloride solution, other alkaline and chloride-containing solutions.
The concentrate is diluted in 250-500 ml of 5% dextrose solution (so that the concentration is not less than 0.2 mg / ml).
The infusion solution should be administered immediately after preparation. Storage at 2–8 ° C is allowed, but no more than 24 hours.
Only a clear solution is allowed to enter. It cannot be used in the event of sediment detection.
It is forbidden to inject Eloxatin undiluted.
Side effects
The classification of the frequency of side effects is distributed according to the following scale: very often -> 1/10, often - from> 1/100 to ≤ 1/10, infrequently - from> 1/1000 to ≤ 1/100, rarely - from> 1/10 000 to ≤ 1/1000, very rarely - ≤ 1/10 000, unknown frequency - it is not possible to determine the frequency from the available data.
Possible side reactions when using oxaliplatin in combination with fluorouracil / calcium folinate:
- general disorders: very often - chills, fever, weakness (due to an immune reaction or the development of an infection, including with febrile neutropenia), asthenia;
- local reactions: very often - pain, edema, hyperemia and thrombosis at the injection site of Eloxatin. If the infusion solution enters the tissue surrounding the vein, local pain and inflammation may appear, sometimes leading to complications (including necrosis);
- from the digestive system: very often - diarrhea, vomiting (in case of severe disorders, it is possible to develop dehydration, intestinal obstruction, hypokalemia, functional disorders of the kidneys, metabolic acidosis, especially with the simultaneous use of fluorouracil), abdominal pain, nausea, mucositis (inflammation of the mucous membranes), stomatitis; often - gastrointestinal bleeding; rarely - colitis (including pseudomembranous, caused by Clostridium difficile), pancreatitis;
- on the part of the hepatobiliary system: very rarely - hepatic sinusoidal obstruction syndrome (veno-occlusive liver disease) or pathological manifestations associated with this syndrome, including pelious hepatitis, perisinusoidal fibrosis, nodular regenerative hyperplasia (may manifest as portal hypertension or increased activity of hepatic transaminases and alkaline phosphatase in serum);
- on the part of the cardiovascular system: very often - nosebleeds; often - increased blood pressure, thromboembolism, deep vein thrombosis;
- from the respiratory system: very often - cough; often - hiccups; rarely - pulmonary fibrosis, acute interstitial lung damage (in some cases fatal);
- on the part of the musculoskeletal system and connective tissue: very often - back pain (in rare cases, they indicate the development of hemolysis; a thorough examination is required when such a reaction occurs); often - arthralgia;
- from the urinary system: very rarely - acute renal failure, acute interstitial nephritis, acute tubular necrosis;
- from the immune system: very often - allergic reactions (urticaria, rhinitis, conjunctivitis); often - a feeling of pain in the chest, angioedema, anaphylactic reactions (including bronchospasm), anaphylactic shock, lowering blood pressure;
- on the part of the skin and subcutaneous tissues: often - alopecia (with oxaliplatin monotherapy - less than 5% of cases);
- on the part of the organ of hearing and the organ of vision: rarely - deafness, optic neuritis, narrowing of the visual fields, transient decrease in visual acuity, transient loss of vision (reversible after discontinuation of Eloxatin);
- from the side of metabolism: very often - anorexia;
- on the part of the blood and lymphatic system: very often - neutropenia, anemia and thrombocytopenia *; often - febrile neutropenia (including grade 3-4); rarely - autoimmune hemolytic anemia and thrombocytopenia;
- on the part of the nervous system: very often - acute neurosensory manifestations ** (usually expressed by transient paresthesia, hypesthesia and dysesthesia; occur more often at the end of a 2-hour infusion of Eloxatin or within a few hours after its end, independently decrease over the next several hours / days, often repeated in subsequent cycles of treatment; may occur or worsen with exposure to cold objects or low temperatures). Acute laryngeal-pharyngeal dysesthesia syndrome develops rarely and is characterized by subjective sensations of dysphagia, shortness of breath or a feeling of suffocation, without objective respiratory disorders (cyanosis, hypoxia) and laryngospasm / bronchospasm (stridor, wheezing). Sometimes there are dysfunctions of the cranial nerves (may be associated with the indicated side effects or be isolated), such as diplopia (double vision), aphonia, dysphonia, impaired tongue sensitivity, dysarthria hoarseness, decreased visual acuity, eye pain, narrowing of the visual fields, facial pains, trigeminal neuralgia. There may also be imbalances, impaired coordination and gait, involuntary muscle contractions, muscle twitching and spasms (including spasm of the masticatory muscles), myoclonus, ataxia, discomfort / feeling of pressure / feeling of pressure / pain in the pharynx or chest; rarely - dysarthria, Lermitte's symptom, disappearance of deep tendon reflexes, reversible parieto-occipital leukoencephalopathy.violation of the sensitivity of the tongue, dysarthria, hoarseness, decreased visual acuity, pain in the eyes, narrowing of the visual fields, facial pain, trigeminal neuralgia. There may also be imbalances, impaired coordination and gait, involuntary muscle contractions, muscle twitching and spasms (including spasm of the masticatory muscles), myoclonus, ataxia, discomfort / feeling of pressure / feeling of pressure / pain in the pharynx or chest; rarely - dysarthria, Lermitte's symptom, disappearance of deep tendon reflexes, reversible parieto-occipital leukoencephalopathy.violation of the sensitivity of the tongue, dysarthria, hoarseness, decreased visual acuity, pain in the eyes, narrowing of the visual fields, facial pain, trigeminal neuralgia. There may also be imbalances, impaired coordination and gait, involuntary muscle contractions, muscle twitching and spasms (including spasm of the masticatory muscles), myoclonus, ataxia, discomfort / feeling of pressure / feeling of pressure / pain in the pharynx or chest; rarely - dysarthria, Lermitte's symptom, disappearance of deep tendon reflexes, reversible parieto-occipital leukoencephalopathy.spasm of the chewing muscles), myoclonus, ataxia, discomfort / feeling of pressure / feeling of constriction / pain in the throat or chest; rarely - dysarthria, Lermitte's symptom, disappearance of deep tendon reflexes, reversible parieto-occipital leukoencephalopathy.spasm of the chewing muscles), myoclonus, ataxia, discomfort / feeling of pressure / feeling of constriction / pain in the pharynx or chest; rarely - dysarthria, Lermitte's symptom, disappearance of deep tendon reflexes, reversible parieto-occipital leukoencephalopathy.
* The incidence of neutropenia, anemia and thrombocytopenia is higher with the use of Eloxatin (at a dose of 85 mg / m 2 once every 2 weeks) in combination with fluorouracil and / or calcium folinate than with monotherapy with the drug at a dose of 130 mg / m 2every 3 weeks [frequency of neutropenia - 70% (with monotherapy - 15%), anemia - 80% (with monotherapy - 60%), thrombocytopenia - 80% (with monotherapy - 40%)]. Severe neutropenia (neutrophil count <1000 / μL) occurs more often with Eloxatin in combination with fluorouracil than with monotherapy with the drug (40% versus 15%). Severe anemia (hemoglobin <8 g / dl) and severe thrombocytopenia (thrombocytopenia <50,000 / μl) occur with approximately the same frequency with drug monotherapy and when oxaliplatin is used in combination with fluorouracil.
** The limiting toxicity of Eloxatin is neurological toxicity, manifested in the form of peripheral sensory neuropathy, characterized by such disorders as peripheral dysesthesia and / or paresthesia, including the development of convulsive muscle contractions, which are often (85–95%) provoked by cold. The severity of these symptoms usually decreases between treatment cycles. With an increase in the number of treatment cycles, the time of their preservation increases. Pain and functional impairment (including difficulty in performing precise movements) are the consequences of sensory impairments. In the event of their occurrence, as well as with an increase in their duration, it is necessary to adjust the dosage regimen of Eloxatin. In some cases, treatment cancellation is required. At a cumulative dose (approximately 800 mg / m 2) over several cycles (eg ten) the risk of functional impairment is ≤ 15%. Neurological manifestations usually decrease after discontinuation of therapy.
Side effects identified during post-marketing research:
- on the part of the blood: the frequency is unknown - hemolytic uremic syndrome;
- from the nervous system: frequency unknown - convulsions.
Overdose
In case of an overdose, the severity of side effects may increase.
The antidote is unknown. Treatment is symptomatic. It is necessary to carefully monitor the hematological parameters and the patient's condition.
special instructions
Eloxatin is used only in specialized oncological departments under the close supervision of an oncologist who has experience working with anticancer drugs.
In the course of treatment, observation is required for the possible development of toxic effects. Regularly (once a week) and before each subsequent administration of Eloxatin, the content of peripheral blood cells, indicators of renal and liver function should be determined.
When using Eloxatin, the standard precautions for cytotoxic drugs must be followed. If the solution gets on the mucous membranes or skin, rinse them immediately and thoroughly with water. In case of extravasation (ingestion of the drug in the tissues surrounding the vein), the infusion solution is immediately stopped and local symptomatic treatment is carried out.
Before each subsequent administration of Eloxatin and periodically between cycles, it is necessary to conduct a neurological examination of the patient in order to timely identify possible signs of neurotoxicity (peripheral sensory neuropathy), especially in the case of the simultaneous use of other drugs with potential neurotoxicity. The physician should inform the patient that after the end of the course of treatment, persistent symptoms of peripheral sensory neuropathy may appear. Symptoms of local mild paresthesias with functional impairments can persist for 3 years after the end of the adjuvant drug therapy.
In cases of development of acute laryngeal-pharyngeal dysesthesia during a 2-hour infusion, the next administration of Eloxatin should be carried out within 6 hours. In order to avoid the development of abnormal sensitivity, patients during the period of therapy are advised to avoid exposure to cold, in particular, do not take too cold food and drinks, avoid hypothermia.
Eloxatin may cause gastrointestinal toxicity with nausea and vomiting. The use of antiemetics can eliminate these symptoms or reduce their severity. Severe diarrhea and / or vomiting may indicate the development of dehydration, paralytic intestinal obstruction, intestinal obstruction, metabolic acidosis, hypokalemia, renal impairment, especially with the simultaneous use of fluorouracil.
Patients should be warned about the need for immediate medical attention in case of diarrhea / vomiting or symptoms of neutropenia.
Symptoms such as headache, visual disturbances (from blurred images to blindness), seizures, and mental impairment, sometimes accompanied by an increase in blood pressure, can be signs of reversible parieto-occipital leukoencephalopathy. The diagnosis is confirmed by computed tomography or magnetic resonance imaging of the brain.
In case of development of toxicity associated with fluorouracil, during the combination therapy, the usual dose adjustment in these cases is used (according to the instructions for use of this drug).
For patients who develop symptoms from the respiratory system (dry cough, wheezing, shortness of breath, lung infiltration on X-ray examination), which cannot be explained otherwise, Eloxatin is temporarily discontinued and an additional lung examination is performed to exclude interstitial pneumonitis.
In the case of a deviation from the norm in the functional parameters of the liver or the development of portal hypertension, which most likely are not the result of the spread of metastases to the liver, a thorough examination of the patient for possible damage to the hepatic vessels is indicated.
Influence on the ability to drive vehicles and complex mechanisms
During the period of therapy, reversible visual impairments (for example, decreased visual acuity or loss of vision) often occur, which pose a danger to patients who drive vehicles and are employed in potentially hazardous industries.
Application during pregnancy and lactation
The introduction of Eloxatin is contraindicated during pregnancy and lactation.
Women and men of reproductive age should use reliable methods of contraception during treatment.
Pediatric use
Eloxatin is intended for use in adults only and is not used in pediatrics.
With impaired renal function
With normal to moderate impairment of renal function, there is no need to adjust the dose of Eloxatin. In severe disorders, the initial dose is reduced to 65 mg / m 2.
There is insufficient data on the safety of the use of Eloxatin in patients with severe functional impairment of the kidneys, so the drug can be prescribed only after a thorough assessment of the balance of benefits and risks. Treatment should be carried out under close control of organ function.
For violations of liver function
In case of normal to moderate impairment of hepatic function, there is no need to adjust the dose of the drug. Before each infusion of Eloxatin and regularly during the entire period of therapy (1 time per week), a study of the functional parameters of the liver should be carried out.
There is no information on the use of oxaliplatin in severely impaired liver function.
Use in the elderly
Elderly patients do not need to adjust the dose of Eloxatin.
Drug interactions
There was no significant change in the pharmacodynamic parameters of oxaliplatin with the simultaneous use of sodium valproate, erythromycin, paclitaxel, granisetron, salicylates.
Eloxatin applied in a dose of 85 mg / m 2 immediately prior to administration of fluorouracil, no effect on the concentration of the latter in the blood.
Oxaliplatin is pharmaceutically incompatible with solutions containing chlorides, sodium chloride 0.9% solution and other saline (alkaline) solutions.
When interacting with aluminum, a decrease in the activity of oxaliplatin and the formation of a precipitate in the solution is possible.
Analogs
Eloxatin analogs are Alkeran, Aranose, Astroglyph, BiKNU, Vero-Ifosfamide, Dacarbazine Lahema, Dakarbazin Medak, Dakarbazin-Lance, Displanor, Ifosfamide, Carboplatin, Carbotera, Leukeran, Lizomilestinomustin, Oxides Platikad, Tezalom, Temodal, Tepadina, Cycloplatin, Exorum, Endoxan, etc.
Terms and conditions of storage
Store in a dark place out of the reach of children at temperatures up to 30 ° C.
The shelf life is 3 years.
Terms of dispensing from pharmacies
Dispensed by prescription.
Reviews about Eloxatin
Given the specificity of the use of the drug, there are practically no reviews of Eloxatin on the network. In rare reports, patients or their relatives note the antitumor efficacy of the drug, but indicate the development of adverse reactions.
Price for Eloxatin in pharmacies
Approximate prices for Eloxatin: 1 bottle of 10 ml - 9800–10,500 rubles, 1 bottle of 20 ml - 20,400–20,500 rubles, 1 bottle of 40 ml - 34,000–38,980 rubles.
Eloxatin: prices in online pharmacies
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Drug name Price Pharmacy |
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Eloxatin 5 mg / ml concentrate for preparation of solution for infusion 10 ml 1 pc. 8600 RUB Buy |
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Eloxatin 5 mg / ml concentrate for preparation of solution for infusion 40 ml 1 pc. RUB 21,500 Buy |
Maria Kulkes Medical journalist About the author
Education: First Moscow State Medical University named after I. M. Sechenov, specialty "General Medicine".
Information about the drug is generalized, provided for informational purposes only and does not replace the official instructions. Self-medication is hazardous to health!
