Eloxatin

Eloxatin is an antitumor drug.

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Indications Eloxatine

It is used in the following cases:

• adjuvant treatment for stage 3 bowel cancer, after radical excision of the primary tumor – together with the use of 5-fluorouracil or calcium folinate;
• disseminated bowel cancer – monotherapy or combination with calcium folinate or 5-fluorouracil;
• cancer in the ovarian area (used as secondary therapy).

Release form

The drug is released in the form of an infusion lyophilisate, in vials with a capacity of 50 or 100 mg. There is 1 such vial in a pack.

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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 with 1,2-diaminocyclohexane. Eloxatin has a wide range of cytotoxic effects, and at the same time it actively affects in vitro, as well as in vivo, various models of neoplasms that are resistant to cisplatin.

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

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Pharmacokinetics

Metabolic and distribution processes.

In vivo processes, the substance oxaliplatin undergoes an active biotransformation process and is not detected in the plasma by the end of a 2-hour injection in a portion of 85 mg/m2 ^. In the blood, 15% of the administered portion is noted, and the remainder (85%) quickly undergoes distribution within tissues or is excreted in the urine. Platinum is synthesized with plasma albumin.

Excretion.

The drug is excreted in the urine during the first 48 hours. On the 5th day, approximately 54% of the entire portion is found in 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 clearance level – from 17.55±2.18 l/hour to 9.95±1.91 l/hour – is observed in renal failure. A decrease in Vd values is also considered statistically important – from 330±40.9 to 241±36.1 l.

The effect of severe renal failure on platinum clearance rates is unknown.

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Dosing and administration

The medication is used exclusively by adults. The intravenous infusion procedure lasts 2-6 hours.

Hyperhydria is not necessary during the use of the therapeutic agent. When combining the substance with 5-fluorouracil, first perform an infusion with the introduction of oxaliplatin, and then use 5-fluorouracil.

In adjuvant treatment of bowel cancer, the drug is administered in a dose calculated at 85 mg/ ^m2. The procedure is performed once every 2 weeks, over 12 treatment cycles (the course is six months).

For disseminated bowel cancer, the above dosage (85 mg/ ^m2 ) is administered once every 14 days, both as monotherapy and together with 5-fluorouracil.

During therapy for ovarian cancer, a dose of 85 mg/ ^m2 is administered once every 14 days as monotherapy or in combination with other chemotherapeutic drugs.

Repeated drug infusions may only be performed if the neutrophil count is >1500/μL and the platelet count is >50,000/μL.

Recommended schemes for correcting portion sizes and the mode of administration of the drug.

If the patient has hematological abnormalities (neutrophil counts <1500/µL or platelet counts <50,000/µL), a new treatment cycle should be postponed until the above parameters are restored.

If grade 4 diarrhea, grade 3-4 neutropenia (neutrophil count <1000/μl), or grade 3-4 thrombocytopenia (platelet count <50,000/μl) develops, the oxaliplatin dose during subsequent infusions should be reduced to 65 mg/m2 ⁽ treatment of ovarian cancer or disseminated colorectal cancer) or 75 mg/m2 ⁽ adjuvant treatment of colorectal cancer), with standard reductions in 5-fluorouracil dosage when used in combination.

For those people who experience acute laryngeal dysesthesia during infusions or several hours after a 2-hour infusion procedure, it is necessary to increase the duration of the new drug infusion to 6 hours.

If pain (a symptom of neurotoxicity) develops and lasts for more than 1 week, the new dosage of the drug should be reduced to 65 mg/m2 ⁽ disseminated bowel cancer or ovarian cancer) or to 75 mg/m2 ⁽ adjuvant treatment of bowel cancer).

If paresthesia occurs without any functional disorders and persists until the start of a new cycle, the next dose of Eloxatin should be reduced to 65 mg/m2 ⁽ disseminated bowel cancer or ovarian cancer) or to 75 mg/m2 ⁽ adjuvant treatment of bowel cancer).

If paresthesias with the development of functional disorders occur and persist until the next treatment cycle, it is necessary to discontinue the use of oxaliplatin. If the severity of signs of neurotoxicity has decreased after discontinuing the use of the drug, the option of resuming therapy can be considered.

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

There is no information regarding the use of the drug in people with severe kidney problems.

Because information on the tolerability of Eloxatin in people with moderate renal impairment is limited, it is necessary to assess the benefits and risks to the patient before starting the procedure. In this group of patients, therapy can be started with the recommended dose. Kidney function should be monitored continuously during treatment.

Scheme of production, and in addition, administration of a medicinal product.

When preparing the drug, as well as during its infusion, it is prohibited to use needles and other equipment if they contain aluminum.

The medicinal element must not be diluted or dissolved with a 0.9% sodium chloride solution, nor must it be mixed with other alkaline (salt) or chloride-containing solutions.

When diluting the lyophilisate, use injection water or 5% dextrose solution. In such a case, it is necessary to add 10 ml of the solvent into the vial with 50 mg of powder (it should be noted that 20 ml of the solvent is poured into a 100 mg vial to obtain a substance with a concentration of 5 mg/ml).

Immediately after the lyophilisate is completely dissolved, it is necessary to begin preparing the infusion solution.

To prepare the infusion substance, add the dissolved drug to a 5% dextrose solution (0.25-0.5 l) so that the concentration of the resulting substance is at least 0.2 mg/ml. The drug should be administered to the patient immediately after its preparation. The solution remains stable for 24 hours when stored at a temperature of 2-8°C.

If sedimentation is observed in the prepared solution, it should be destroyed. Only a transparent substance can be administered to the patient.

Oxaliplatin must not be mixed with other drugs (especially folinic acid and 5-fluorouracil) in the same infusion device. It is also contraindicated to administer the undiluted substance.

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Use Eloxatine during pregnancy

Eloxatin should not be administered to pregnant or breastfeeding women.

Men and women of childbearing age should use reliable contraception during treatment with the drug.

Contraindications

Main contraindications:

• the presence of myelosuppression before the start of the 1st course of treatment with neutrophil counts below 2000/μl or platelets below 100,000/μl;
• sensory polyneuropathy before the start of the 1st course of therapy;
• severe kidney problems (CC values below 30 ml/minute);
• the presence of high sensitivity to oxaliplatin.

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Side effects Eloxatine

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

• disorders of hematopoietic function: leukopenia, thrombocyto-, neutro- or lymphopenia, as well as anemia, are often observed. Neutropenic fever (also grades 3-4) and sepsis against its background often develop. Thrombocytopenia of immune origin and hemolytic anemia are occasionally observed;
• digestive disorders: vomiting, stomatitis, diarrhea, constipation, nausea, stomach pain, mucositis often occur, as well as loss of appetite and increased activity of liver enzymes, LDH, ALP and bilirubin levels. Hiccups, dyspepsia and GERD often occur. Intestinal obstruction may develop. Colitis (sometimes its pseudomembranous form) is occasionally observed;
• CNS and PNS lesions: in most cases, sensory disturbances, sensory polyneuropathy, asthenia, and headaches are observed. Depression, Dupre's disease, and insomnia are often observed. A feeling of severe nervousness may occur. Dysarthria develops rarely. The severity of neurotoxicity depends on the dose size of the drug. Signs of sensory polyneuropathy are often caused by cold. The duration of these manifestations (they usually subside between treatment courses) increases in accordance with the total dose size of oxaliplatin. Functional disorders (problems with precise movements) may be a consequence of sensory impairment. After stopping therapy, the severity of neurological signs usually decreases or disappears completely. In 3% of patients, after 3 years from the end of therapy, local persistent paresthesias of a moderate form (2.3%) or paresthesias affecting functional activity (0.5%) were observed. Acute neurosensory symptoms have been observed during oxaliplatin infusion, usually developing within a few hours after drug administration and often induced by cold. They manifested as temporary paresthesia, hypoesthesia, or dysesthesia. Acute laryngeal-pharyngeal dysesthesia syndrome was observed rarely. It manifested itself as dyspnea with dysphagia, without objective symptoms of RDS (hypoxia or cyanosis), and in addition, spasm of the bronchi (wheezing or stridor were not observed) or larynx. In addition, such signs as lingual dysesthesia, spasm in the jaw muscles, a feeling of pressure in the sternum, and dysarthria appeared. Such manifestations usually passed quickly without the use of drugs (although sometimes they were eliminated with bronchodilators and antihistamines). Prolongation of the infusion procedure during new treatment cycles can reduce the incidence of this syndrome;
• Musculoskeletal dysfunction: back pain often develops. Bone pain and arthralgia may also develop;
• respiratory system disorders: dyspnea and cough are common. Runny nose and infections affecting the upper respiratory tract sometimes occur. Pulmonary fibrosis is rare;
• problems with the functioning of the cardiovascular system: often there is pain behind the breastbone, thromboembolism in the area of the pulmonary arteries, as well as thrombophlebitis affecting the deep veins;
• urinary dysfunction: dysuria or hematuria often develop;
• dermatological disorders: skin rash and alopecia are common. Sometimes erythematous rash, scaling of the skin on the feet and palms, nail problems and hyperhidrosis appear;
• problems with hearing and vision: sometimes visual disturbances and conjunctivitis appear. Occasionally, neuritis occurs in the area of the auditory nerve, hearing loss, temporary weakening of vision and visual field slippage;
• allergy symptoms: occasionally (with monotherapy) or often (with simultaneous administration with calcium folinate or 5-fluorouracil), bronchial spasms, anaphylaxis, Quincke's edema and decreased blood pressure values occur. Allergic symptoms often develop in the form of rashes (often urticaria), runny nose or conjunctivitis;
• local lesions: when the drug is extravasated, inflammation and pain occur at the injection site;
• laboratory test results: hypokalemia and glucose-sodium imbalance in the blood serum are often noted. Creatinine levels often increase;
• Others: Often there is a feeling of extreme fatigue, a noticeable increase in temperature or weight, and a taste disorder.

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Overdose

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

If disorders develop, the patient's condition should be closely monitored (including hematological monitoring), and symptomatic measures should be taken. Eloxatin has no antidote.

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Interactions with other drugs

No significant changes in the indices of protein synthesis of oxaliplatin in blood plasma are observed when combining the drug with salicylates or the drug erythromycin, as well as sodium valproate and the drugs paclitaxel and granisetron.

The medication is not compatible with chloride-containing and alkaline solutions.

The combination of Eloxatin with aluminum may cause the formation of a precipitate and a decrease in the activity of oxaliplatin.

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Storage conditions

Eloxatin should be stored in a place out of the reach of small children, at a temperature not exceeding 30°C.

Shelf life

Eloxatin can be used for 3 years from the date of manufacture of the drug.

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Application for children

The medicine is prohibited for use in children.

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Analogues

Analogues of the drug are Oxaliplatin Medak, Oxaliplatin-Filaxis, Oxaliplatin-Teva, Oxaliplatin Lahema, and in addition Oxatera, Platicad with Oxaliplatin-Ebeve and Plaxat with Exorum.

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