Eloxatin

Eloxatin is an antitumor drug.

[1], [2], [3]

Indications of the eloxatin

Applicable in the following cases:

• adjuvant treatment for bowel cancer of the 3rd stage, after performing radical excision of the primary tumor - together with the use of 5-fluorouracil or calcium folinate;
• colon cancer of a disseminated nature - monotherapy or combination with calcium folate or 5-fluorouracil;
• cancer in the ovaries (used as a secondary therapy).

Release form

Release of the drug is carried out in the form of infusion lyophilizate, in flakonchikah capacity of 50 or 100 mg. In a pack - 1 such a bottle.

[4]

Pharmacodynamics

The drug has an antitumor effect. It is a platinum derivative, within its molecular structure, the platinum atom forms a compound with oxalate, and in addition to 1,2-diaminocyclohexane. Eloxatin has a wide range of cytotoxic effects, and at the same time it actively influences in vitro and also in vivo on a variety of models of neoplasms that have resistance to cisplatin.

The medicinal effect of the drug is due to the fact that it interacts with DNA, forming intra- and interspiral bridges, as well as inhibiting the process of DNA binding.

[5]

Pharmacokinetics

Metabolic and distribution processes.

In vivo processes, the oxaliplatin substance undergoes an active biotransformation process, and is not detectable inside the plasma even at the end of the 2-hour injection in a dose of 85 mg / m ². Inside the blood, 15% of the administered dose is noted, and the remainder (85%) quickly passes the distribution inside the tissues or is excreted in the urine. Platinum is synthesized with plasma albumin.

Excretion.

The drug is excreted in the urine for the first 48 hours. On the 5th day, about 54% of the whole portion is noted inside the urine, and even less than 3% is found in the feces.

Pharmacokinetic parameters in the presence of clinical disorders.

A significant decrease in the level of clearance - from the rate of 17.55 ± 2.18 liters / hour to the level of 9.95 ± 1.91 liters / hour - is noted with kidney failure. It is also statistically important to reduce the Vd values from a level of 330 ± 40.9 to a mark of 241 ± 36.1 liters.

What impact on the parameters of clearance of platinum have severe stages of kidney failure - it is not known.

[6], [7], [8], [9], [10]

Dosing and administration

The medication is used exclusively by an adult. The procedure of intravenous infusion lasts 2-6 hours.

Hyperhydria during the use of a therapeutic agent is not needed. When a substance is combined with 5-fluorouracil, an infusion with the administration of oxaliplatin should be first performed, and then 5-fluorouracil should be used.

With adjuvant treatment of bowel cancer, medication is administered in a dose that is calculated at a ratio of 85 mg / m ². The procedure is carried out once for 2 weeks, during 12 treatment cycles (the course is six months).

In case of intestinal cancer of disseminated nature, the above dosage (85 mg / m ² ) is administered once for 14 days both as monotherapy and together with the substance 5-fluorouracil.

During therapy with cancer in the ovary region, a dose of 85 mg / m ² is administered once for 14 days in the form of monotherapy or in conjunction with other chemotherapeutic drugs.

Repeated drug infusions can be performed only in those cases where the neutrophil count is> 1500 / μL, and the platelet count is> 50000 / μL.

Recommended schemes for correcting the size of portions, as well as the mode of administration of the drug.

If the patient has hematologic disorders (neutrophil counts are <1500 / μl, or platelet count is <50000 / μL), the new treatment cycle should be deferred until the above mentioned parameters are restored.

If diarrhea develops in the 4th stage of toxicity, neutropenia having stage 3-4 (neutrophil count is <1000 / μl) or thrombocytopenia of the 3rd degree (platelet level is <50000 / μl), the size of the oxaliplatin portion during the following infusions should be reduced to 65 mg / m ² (elimination of cancer in the ovarian or colon cancer of a disseminated nature) or up to 75 mg / m ² (adjuvant bowel cancer treatment) in combination with a standard dose reduction of 5-fluorouracil with their combination.

Those people who have infusions or a few hours after a 2-hour infusion procedure begin acute dysesthesia of the laryngeal-pharyngeal character, it is necessary to increase the duration of a new infusion of drugs to 6 hours.

When pain develops (a symptom of neurotoxicity), which lasts more than 1 week, the new dosage of the drug should be reduced to 65 mg / m ² (intestinal cancer that is disseminated, or cancer in the ovaries) or up to 75 mg / m ² (adjuvant treatment of bowel cancer).

If there is paresthesia, against which there are no functional disorders, and which persist before the start of a new cycle, another portion of Eloxatin should be reduced to 65 mg / m ² (disseminated form of intestinal cancer or cancer in the ovaries) or up to 75 mg / m ² (adjuvant treatment of bowel cancer).

With the advent of paresthesias with the development of functional disorders that persist until a new treatment cycle, it is necessary to abolish the use of oxaliplatin. If the severity of signs of neurotoxicity decreased after discontinuation of drug use, it may be considered a variant with the resumption of therapy.

If stomatitis or mucositis occurs on the 2nd or higher stage of toxicity, therapy should be stopped until they are eliminated or toxicity symptoms are reduced to the 1st stage.

There is no information on the use of medication in people with disorders in the work of the kidneys in a severe degree.

Because the information about the tolerance of Eloxatin to people with a moderate stage of renal function disorder is limited, it is necessary to evaluate the benefit, as well as the risk for the treating person from the introduction before the procedures are started. In this group of patients, treatment can begin with the recommended portion. During treatment, you must constantly monitor the work of the kidneys.

The manufacturing scheme, and in addition to this drug administration.

In the manufacture of drugs, as well as its infusion, it is prohibited to use needles and other equipment if they contain aluminum.

Do not dilute or dilute the drug element with 0.9% sodium chloride solution, and in addition mix with other alkaline (salt) or chloride-containing solutions.

When diluting the lyophilisate, injectable water or a 5% solution of dextrose should be used. In this case, add 10 ml of a solvent to the inside of the 50 mg powder bottle (note that 20 ml of solvent is poured into a 100-mg bottle to produce a substance having a concentration of 5 mg / ml).

Immediately after the lyophilizate has completely dissolved, it is necessary to start preparing the infusion solution.

To make an infusion substance, it is necessary to add the dissolved preparation in a 5% dextrose solution (0.25-0.5 L) so that the concentration of the substance obtained is at least 0.2 mg / ml. The patient should be given medicine immediately after it is manufactured. The solution remains stable for 24 hours when stored at a temperature of 2-8 ° C.

If precipitation occurs in the prepared solution, it should be destroyed. The patient can be administered an exclusively transparent substance.

Oxaliplatin should not be mixed within one infusion set with other drugs (especially folinic acid and 5-fluorouracil). It is also contraindicated to inject undiluted substance.

[14], [15]

Use of the eloxatin during pregnancy

Eloxatin should not be given to pregnant women, nor to breast-feeding mothers.

Men and women who are at the fertile age must use reliable contraceptives during the treatment with the drug.

Contraindications

The main contraindications:

• presence of myelosuppression before the beginning of the first treatment course with neutrophil counts below 2000 / μL or platelets below 100,000 / μL;
• polyneuropathy of a sensory character before the start of the first therapeutic course;
• problems with kidney function in a pronounced form (CC values below 30 ml / minute);
• presence of high sensitivity to oxaliplatin.

[11], [12]

Side effects of the eloxatin

The use of the drug may cause the appearance of side effects:

• disorders of the hematopoietic function: leuko-, thrombocytopenia, neutropenic or lymphopenia are often noted, as well as anemia. Often develops neutropenic fever (also 3-4 degrees) and sepsis on its background. Occasionally, thrombocytopenia of the immune origin and hemolytic anemia are noted;
• disorders of digestive activity: often there are vomiting, stomatitis, diarrhea, constipation, nausea, stomach pains, mucositis, and in addition loss of appetite and increased activity of liver enzymes, LDH, SHF and bilirubin. Often there is hiccough, dyspepsia and GERD. Possible development of intestinal obstruction. Occasionally there is colitis (at times its pseudomembranous form);
• lesions in the central nervous system and PNS: in most cases, sensitivity disorders, sensory-like polyneuropathy, asthenia and headaches are observed. Often, depression is noted, Dupree's disease and insomnia. There may be a feeling of strong nervousness. Dysarthria develops occasionally. The severity of neurotoxicity depends on the size of the portion of the drug. Symptoms of sensory polyneuropathy are often caused by cold. The duration of these manifestations (they are usually stopped in the intervals between treatment courses) is increased in accordance with the total size of the oxaliplatin dose. Functional disorders (problems with the implementation of precise movements) can be a consequence of sensory impairment. After stopping therapy, the degree of neurological signs is usually reduced or they completely disappear. In 3% of patients after 3 years after the completion of therapy, local stable paresthesias with moderate form (2.3%) or paresthesia affecting functional activity (0.5%) were observed. When oxaliplatin was infused, neurosensory symptoms were observed in the acute stage, usually developing for several hours after the use of drugs and often caused by the effects of cold. They were manifested in the form of temporary paresthesia, hypesthesia or dysesthesia. Occasionally there was a syndrome of dysesthesia of the laryngeal-pharyngeal nature in acute form. His manifestation was dyspnea with dysphagia, without the presence of objective symptoms of RDS (hypoxia or cyanosis), and in addition to spasm of the bronchi (wheezing or stridor were not observed) or larynx. In addition, there were signs such as language dysesthesia, spasm in the jaw musculature, a pressing feeling in the sternum and dysarthria. Such manifestations usually quickly passed without the use of drugs (although sometimes they were eliminated with the help of bronchodilators and antihistamines). Renewal of the infusion procedure during new treatment cycles may reduce the incidence of this syndrome;
• violations of musculoskeletal function: often develop pain in the back. Also, the appearance of pain in the bones and the development of arthralgia;
• disorders in the work of the respiratory system: often marked dyspnea and cough. Sometimes there is a runny nose and infections that affect the upper part of the respiratory ducts. Occasionally, pulmonary fibrosis is noted;
• problems in the work of the CAS: often pain in the chest, thromboembolism in the arteries of the lungs, as well as thrombophlebitis affecting the deep veins;
• disorders of urinary function: often there is a development of dysuria or hematuria;
• dermatological disorders: skin rash and alopecia are often noted. Sometimes there is an erythematous rash, skin peeling in the area of the feet and palms, problems with the nails and hyperhidrosis;
• problems with auditory and visual function: sometimes there are visual disturbances and conjunctivitis. Occasionally, neuritis arises in the area of the auditory nerve, weakening of the hearing, transient weakening of vision and slipping of the visual fields;
• symptoms of allergy: occasionally (with monotherapy) or often (with the simultaneous administration of calcium folinate or 5-fluorouracil substance), bronchial spasms, anaphylaxis, Quincke edema and a decrease in blood pressure appear. Often develop allergic symptoms in the form of rashes (often hives), a cold or conjunctivitis;
• local lesions: with extravasation of drugs, inflammation and pain occur on the injection site;
• indications of laboratory tests: often note hypokalemia and a disorder of the balance of glucose with sodium inside the blood serum. The rates of creatinine often increase;
• others: often there is a feeling of severe fatigue, a noticeable increase in temperature or weight, as well as a taste disorder.

[13]

Overdose

Manifestations of intoxication: in case of overdose, the severity of the above-mentioned side symptoms may be potentiated.

In the development of violations should carefully monitor the patient's condition (to conduct, among other things, hematological control), and in addition to perform symptomatic measures. Eloxatin has no antidote.

[16], [17],

Interactions with other drugs

There is no significant change in the protein synthesis of oxaliplatin inside the blood plasma in the combination of drugs with salicylates or the drug erythromycin, as well as sodium valproate and paclitaxel and granisetron medicines.

The drug does not have compatibility with chloride-containing and alkaline solutions.

The combination of Eloxatin and aluminum can cause precipitation, as well as a decrease in the activity of oxaliplatin.

[18], [19], [20]

Storage conditions

Eloxatin should be kept in a place closed from small children, at temperatures not exceeding 30 ° C.

Shelf life

Eloxatin is allowed to be used for 3 years from the date of manufacture of the drug.

[21], [22], [23]

Application for children

The medicine is forbidden to apply to children.

[24],

Analogues

Analogues of the medication are Oxaliplatin Medak, Oxaliplatin-Filaxis, Oxaliplatin-Teva, Oxaliplatinum Lahema, and in addition Oxter, Platikad with Oxaliplatin-Ebewe and Plaksat with Exorum.

[25], [26], [27], [28], [29]