ELOKSATIN
Active material: Oxaliplatin
When ATH: L01XA03
CCF: Anticancer drug
ICD-10 codes (testimony): C18, C19, C20, C56
When CSF: 22.01.02
Manufacturer: SANOFI-AVENTIS France (France)
PHARMACEUTICAL FORM, COMPOSITION AND PACKAGING
Concentrate for solution for infusion in the form of a clear colorless solution.
| 1 ml | |
| oxaliplatin | 5 mg |
Excipients: water d / and.
10 ml – colorless glass vials (1) – packings Valium planimetric (1) – packs cardboard.
20 ml – colorless glass vials (1) – packings Valium planimetric (1) – packs cardboard.
40 ml – colorless glass vials (1) – packings Valium planimetric (1) – packs cardboard.
Pharmacological action
Anticancer drug, platinum derivatives, in the molecular structure of which the platinum atom forms a complex with oxalate and 1,2-diaminocyclohexane. Eloxatin® has a wide range of cytotoxic effects, and also exhibits activity in vitro and in vivo on various tumor models, resistant to cisplatinu.
The study of the mechanism of action of oxaliplatin confirms the hypothesis that, that biotransformed aqueous derivatives of oxaliplatin interact with DNA by forming inter- and intrastranded bridges inhibit DNA synthesis, this is due to the cytotoxicity of the drug and the antitumor effect.
In combination with 5-fluorouracil, a synergistic cytotoxic action is observed.
Pharmacokinetics
Distribution and metabolism
In vivo, oxaliplatin is actively biotransformed and is not detected in plasma already by the end of the 2-hour dose 85 mg / m2, wherein 15% the administered dose is in the blood, and the remaining 85% quickly spread over tissues (or excreted in the urine). Platinum is bound to plasma albumin.
Deduction
Excreted in the urine within the first 48 no. By the fifth day around 54% total dose is found in the urine and less 3% – Calais.
Pharmacokinetics in special clinical situations
A significant decrease in clearance from 17.55 ± 2.18 L / h to 9.95 ± 1.91 L / h was observed in renal failure along with a statistically significant decrease in Vd from 330 ± 40.9 to 241 ± 36.1 l. Influence of severe renal impairment on platinum clearance has not been studied.
Testimony
- adjuvant therapy for stage III colorectal cancer (From to Duke) after radical resection of the primary tumor in combination with 5-fluorouracil / folinic acid;
- disseminated colorectal cancer in the form of monotherapy or combination therapy with 5-fluorouracil / folinic acid;
-ovarian cancer (as a 2nd line of therapy).
Dosage regimen
Eloxatin® appoint only adult in the form of intravenous infusions during 2-6 no.
No overhydration is required with oxaliplatin. If Oxaliplatin is used in combination with 5-fluorouracil, infusion of oxaliplatin must precede the administration of 5-fluorouracil.
To adjuvant therapy of colorectal cancer the drug is administered in a dose based on 85 mg / m2 1 once every 2 weeks during 12 cycles (6 Months).
To treatment of disseminated colorectal cancer - calculated 85 mg / m2 1 once every 2 weeks as monotherapy or in combination with 5-fluorouracil.
To ovarian cancer treatment – by 85 mg / m2 1 once every 2 weeks as monotherapy or in combination with other chemotherapy drugs.
Repeated introduction of Oxaliplatin is produced only when the number of neutrophils >1500/l and platelet >50 000/l.
Recommendations for the correction of the dose and regimen of Oxaliplatin
With hematological disorders (the number of neutrophils <1500/MKL and/or thrombocytes <50 000/l) the next course is postponed until laboratory parameters are restored.
With the development of diarrhea 4 toxicity (on a scale of who), neutropenia 3-4 degrees (the number of neutrophils <1000/l), thrombocytopenia 3-4 degrees (platelet count <50 000/l) the dose of oxaliplatin on subsequent administrations should be reduced from 85 mg / m2 to 65 mg / m2 in the treatment of disseminated colorectal cancer and ovarian cancer; and to 75 mg / m2 in the adjuvant therapy of colorectal cancer in addition to the usual dose reduction of 5-fluorouracil in the case of their combined use.
Patients, who develop acute laryngeal-pharyngeal dysesthesia during infusion or within a few hours after a 2-hour infusion, the next Oxaliplatin infusion should be conducted over a 6 no.
When the pain (as a sign of neurotoxicity) lasting more than 7 days, the subsequent dose of oxaliplatin should be reduced from 85 mg / m2 to 65 mg / m2 in the treatment of disseminated colorectal cancer and ovarian cancer; and to 75 mg / m2 in adjuvant therapy of colorectal cancer.
With paresthesia without functional impairment, continued to next cycle, the subsequent dose of oxaliplatin should be reduced from 85 mg / m2 to 65 mg / m2 in the treatment of disseminated colorectal cancer and ovarian cancer; and to 75 mg / m2 in adjuvant therapy of colorectal cancer.
With paresthesia with functional impairment, continued to next cycle, Oxaliplatin should be abolished; with a decrease in the severity of symptoms of neurotoxicity after discontinuation of oxaliplatin, the question of resuming treatment can be considered.
With the development of stomatitis and / or mucositis 2 and more degree of toxicity, treatment with oxaliplatin should be suspended until they stop or the manifestations of toxicity decrease to 1 degrees.
Data on the use of the drug in patients with severe renal impairment no. Due to the limited data on the safety and tolerability of the drug, patients with moderate renal dysfunction, before using oxaliplatin, the balance of benefits and risks for the patient should be weighed. Therapy in this category of patients can be started with the recommended dose., under the close supervision of the kidney. At mild renal impairment no dose adjustment of oxaliplatin is required.
No dosage changes are required in patients with mild to moderate hepatic impairment. There are no data on the use of oxaliplatin in patients with severely impaired liver function..
Safety profile of oxaliplatin as a monotherapy drug or in combination with 5-fluorouracil in older patients 65 years is the same as, which occurs in younger patients.
Terms of preparation and administration of the solution
During preparation and administration of Eloxatin® needles and other equipment must not be used, aluminum-containing.
Do not dissolve and do not dilute 0.9% sodium chloride solution and do not mix with other saline (alkaline) solutions or solutions, containing chlorides.
Eloxatin concentrate for the preparation of infusion solution® diluted in 250-500 ml 5% dextrose solution to obtain a concentration of at least 0.2 mg / ml. Solution for infusion is recommended to be used immediately after preparation. Infusion solution remains stable for 24 hours at a temperature of from 2 ° to 8 ° C..
Solution showing signs of falling sludge should be destroyed. You can use only transparent solution.
Oxaliplatin solution should not be mixed in the same infusion set with other drugs, especially 5-fluorouracil and calcium folinate. The drug cannot enter straight.
Side effect
Determination of the frequency of adverse reactions: Often (>1/10), often (>1/100, <1/10); sometimes (>1/1000, <1/100); rarely (>1/10 000, <1/1000); rarely (< 1/10 000), including isolated reports.
From the hematopoietic system: Often – anemia, leukopenia, neutropenia, thrombocytopenia, lymphopenia; often – febrile neutropenia (including 3-4 degree), sepsis amid neutropenia; rarely – gemoliticheskaya anemia, immune thrombocytopenia, hemolytic uremic syndrome.
From the digestive system: Often – nausea, vomiting, diarrhea, stomatitis, mukozit, pain in the stomach, constipation, loss of appetite, increase in AP, liver enzymes, the content of bilirubin, LDH; often – dyspepsia, hastroэzofahealnыy reflux, Ikotech, gastrointestinal bleeding; sometimes – ileus; rarely – colitis, including cases psevdomembranoznogo colitis.
From the central and peripheral nervous system: very common - peripheral sensory neuropathy, sensory disturbances, headache, asthenia; often – dizziness, meningism, depression, insomnia; sometimes - increased nervousness; rarely – dysarthria. Neurotoxicity is the dozolimitiruûŝim factor. Symptoms of sensory neuropathy are often triggered by cold. The duration of these symptoms, which usually stopped between courses, increases depending on the total dose of Oxaliplatin. Functional disorders in the form of difficulty in performing precise movements are possible consequences of sensory damage.. The risk of functional disorders with a total dose of about 850 mg / m2 (10 cycles) is about 10%, reaching 20% in the case of total dose 1020 mg / m2 (12 cycles). After stopping treatment, in most cases, the severity of neurological symptoms decreases or they completely stop.. In 3% patients through 3 years after the end of treatment, persistent local paresthesias of moderate intensity were observed (2.3%), or paresthesia, affect the functional activity (0.5%).
Treatment with Oxaliplatin marked acute manifestations of nejrosensornye, which usually occurred within a few hours after drug administration and were most often triggered by exposure to cold. They were characterized by transient paresteziej, dizesteziej or gipesteziej, rarely (1-2%) – acute gortanno syndrome-pharyngeal dizestezii. The latter showed a subjective sense of dysphagia and shortness of breath without objective signs of respiratory distress syndrome (cyanosis or hypoxia), or a spasm of the larynx, or bronchospasm (No stridor or wheezing). Also experienced such phenomenon, like a jaw muscle spasm, dizestesia language, dysarthria and pressure sensation in the chest. Usually these symptoms quickly stoped as without the use of drug therapy, and with the introduction of antihistamines and bronchodilators. Increasing the duration of infusion with subsequent cycles of oxaliplatin therapy can reduce the incidence of this syndrome..
On the part of the musculoskeletal system: Often – back pain; often – arthralgia, ostealgias.
The respiratory system: Often – cough, breathlessness; often – rhinitis, upper respiratory tract infection; rarely – fibrosis lyegkikh.
Cardio-vascular system: often – chest pain, nosebleeds, deep vein thrombophlebitis, tromboembolia pulmonary artery, arterial hypertension.
From the urinary system: often – hematuria, dizurija; rarely – lower nephron syndrome, acute interstitial nephritis, acute renal failure.
Dermatological reactions: Often – alopecia, skin rashes; often – skin peeling palms and feet, erythematous rash, increased sweating, violations by nails.
On the part of the organs of sight and hearing: often – conjunctivitis, visual impairment; rarely – the transitory reduction of Visual acuity, the fields of vision loss, hearing loss, neuritis of the auditory nerve, deafness.
Allergic reactions: rarely (when used as monotherapy) or often (in combination with 5-fluorouracil +/- calcium folinate) bronchospasm may occur, angioedema, hypotension, anaphylactic shock. Cases of such allergic manifestations were often noted, like a rash (especially urticaria), conjunctivitis or rhinitis.
Local reactions: When drug extravasation – pain and inflammatory reactions at the injection.
From the laboratory parameters: Often – kaliopenia, violations of sodium and glucose in serum; often – increased creatinine.
Other: Often – fever, increased fatigue, weight gain, taste disturbances.
Contraindications
- myelosuppression (the number of neutrophils <2000/MKL and/or thrombocytes <100 000/l) before the start of the first course of therapy;
- peripheral sensory neuropathy with functional impairment before the start of the first course of therapy;
- Expressed by the human kidney (CC <30 ml / min);
- Pregnancy;
- Lactation (breast-feeding);
- Hypersensitivity to the drug.
Pregnancy and lactation
Eloxatin® contraindicated during pregnancy and lactation (breast-feeding).
Women and men of childbearing age while using the drug should use reliable methods of contraception.
Cautions
Eloxatin® should only be used in specialized oncology departments and under the supervision of a qualified oncologist. During treatment with oxaliplatin, it is necessary to constantly monitor the patient's condition to identify possible toxic effects.
Regularly (1 once a week), as well as before each administration of Eloxatin® a peripheral blood test should be performed, indicators of liver and kidneys.
Neurologic examination should be performed prior to each administration and during treatment to identify possible symptoms of neurotoxicity..
Patients should be informed about the possibilities of sustainable symptoms of peripheral sensory neuropathy after treatment. Local moderate paresthesias with functional impairments can last up to 3 years after the end of treatment with the drug adjuvantny schema.
With the emergence of respiratory symptoms (dry cough, dyspnoea, wheezing or identifying pulmonary infiltrates with x-ray study), oxaliplatin treatment should be suspended until the presence of interstitial pneumonitis has been ruled out.
Symptoms such as dehydration, paralytic ileus, bowel obstruction, kaliopenia, metabolic acidosis and renal failure can be caused by diarrhoea or vomiting expressed, especially when using oxaliplatin in combination with 5-fluorouracil.
Patients with a history of allergic reactions to other platinum compounds should be monitored for allergic symptoms. In the case of reaction to Oxaliplatin, such anaphylactic, infuziu should immediately suspend and appoint appropriate symptomatic treatment. Further use of oxaliplatin in case of allergic reactions is contraindicated.
If extravasation occurs, the infusion should be stopped immediately and local symptomatic treatment initiated. The remainder of the dose of the drug should enter into another vein.
All normal instructions must be followed when using the drug., taken for the application of cytotoxic drugs. If Eloxatin powder gets in®, its concentrate or solution for infusion on the skin or mucous membranes, should be washed off immediately and thoroughly with water.
Overdose
Symptoms: in case of overdose, the described side effects may increase.
Treatment: careful monitoring of the patient's condition (incl. haematological monitoring); symptomatic therapy. Antidote unknown.
Drug Interactions
Significant changes in the binding of oxaliplatin to blood plasma proteins in vitro when used simultaneously with erythromycin, salicylates, granisetronom, paclitaxel, sodium valproate was not observed.
Pharmaceutical interaction
The drug is incompatible with 0.9% solution of sodium chloride and other salt (alkaline) solutions or solutions, containing chlorides.
When interacting with aluminum possibly education sludge and reduced activity of Oxaliplatin.
Conditions of supply of pharmacies
The drug is released under the prescription.
Conditions and terms
List B. The drug should be stored out of reach of children, dark place at a temperature no higher than 30 ° C. Shelf life – 3 year.
