Exorum, vial, 100mg

Composition

One bottle contains 50 mg of oxaliplatin. Excipients: lactose monohydrate.

Pharmacological action

of Pharmacodynamics . Oxaliplatin is an antitumor drug belonging to a new class of platinum derivatives, in which the platinum atom forms a complex with oxalate and 1,2-diaminocyclohexane. Oxaliplatin exhibits a wide range of cytotoxic effects. It is also active in vitro and in vivo in various cisplatin-resistant tumor models. In combination with 5-fluorouracil, a synergistic cytotoxic effect is observed. The study of the mechanism of action of oxaliplatin confirms the hypothesis that biotransformed, aqueous derivatives of oxaliplatin interact with DNA by forming inter-and inter-stranded bridges and inhibit DNA synthesis, which leads to cytotoxicity and antitumor effect. In vivo, oxaliplatin undergoes active biotransformation and is not detected in plasma by the end of 2-hour use at a dose of 85 mg / m, while 15% of the administered platinum is in the blood, and the remaining 85% is quickly distributed to tissues or excreted in the urine. Platinum binds to plasma albumin and is excreted in the urine within the first 48 hours. By the fifth day, about 54% of the total dose is detected in the urine and less than 3% in the feces. In patients with renal insufficiency, a significant decrease in oxaliplatin Cl is observed from (17.6±2.18) l / h to (9.95±1.91) l / h. The effect of severe renal failure on platinum clearance has not yet been studied.

Indications

Disseminated colorectal cancer (as monotherapy or combination therapy in combination with fluoropyrimidines).

Contraindications

hypersensitivity to oxaliplatin or other components of the drug; myelosuppression (neutrophil count); peripheral sensory neuropathy with functional disorders before the first course of treatment;severe renal dysfunction (creatinine clearance); pregnancy; breast-feeding period.

Side effects

the Frequency of adverse reactions listed below is set out in accordance with the following gradation: very often (>1/10); often (>1/100, ≤1/10), sometimes (>1/1000, ≤1/100); rare (>1/10000, ≤1/1000); very rare (≤1/10,000 sec), including individual messages. From the hematopoietic system: very often — anemia, leukopenia, neutropenia, thrombocytopenia, lymphopenia; often-febrile neutropenia (including grade 3-4), sepsis on the background of neutropenia; rarely-hemolytic anemia, immune thrombocytopenia. From the digestive system: very often-nausea, vomiting, diarrhea, stomatitis, mucositis, stomach pain, constipation, loss of appetite; often-dyspepsia, gastroesophageal reflux, hiccups; sometimes-intestinal obstruction; rarely-colitis, including cases of pseudomembranous colitis. From the central nervous system and peripheral nervous system: very often — peripheral sensorineural neuropathy, sensitivity disorders, headache, asthenia; often-dizziness, meningism, depression, insomnia; sometimes-increased nervousness; rarely-dysarthria. Neurotoxicity is a dose-limiting side effect. Often, the symptoms of sensory neuropathy are triggered by cold. The duration of these symptoms, which are usually relieved between courses, increases depending on the total dose of oxaliplatin. Functional disorders, which are expressed by difficulty performing precise movements, are possible consequences of sensory damage. The risk of functional impairment for a total dose of about 850 mg/m2 (10 cycles) is about 10%, reaching 20% for a total dose of 1020 mg/m2 (12 cycles). In most cases, neurological symptoms improve or disappear altogether after treatment is discontinued. However,3% of patients experienced either persistent localized moderate-intensity paresthesias (2.3%) or paresthesias affecting functional activity (0.5%) 3 years after the end of treatment. Against the background of oxaliplatin treatment, acute sensorineural manifestations were noted, which usually occurred within a few hours after use of the drug and were most often provoked by cold. They were characterized by transient paresthesia, dysesthesia or hypesthesia, rarely (1-2%) — acute laryngopharyngeal dysesthesia syndrome. The latter was manifested by a subjective feeling of dysphagia and shortness of breath without objective signs of respiratory distress syndrome (cyanosis or hypoxia), or laryngeal spasm or bronchospasm (without stridor or wheezing). There were also symptoms such as jaw muscle spasms, tongue dysesthesia, dysarthria, and chest pressure. Usually, these symptoms were quickly relieved both without the use of medication, and with the introduction of antihistamines and bronchodilators. Increasing the infusion time during subsequent cycles of oxaliplatin therapy reduces the frequency of this syndrome. From the musculoskeletal system: very often — back pain; often-arthralgia, bone pain. From the respiratory system: very often — cough, shortness of breath; often — rhinitis, upper respiratory tract infections; rarely — pulmonary fibrosis. From the cardiovascular system: often-pain behind the sternum, deep vein thrombophlebitis, pulmonary embolism. From the urinary system: often-hematuria, dysuria. From the skin and skin appendages: very often — alopecia, skin rashes; often-peeling of the skin of the palms and feet, erythematous rashes, increased sweating, nail disorders. From the side of the organs of vision and hearing: often-conjunctivitis, visual disturbances; rarely-transient decrease in visual acuity, loss of visual fields, hearing loss, neuritis of the auditory nerve. Allergic reactions: rarely (with monotherapy) or often (in combination with 5-fluorouracil + calcium folinate), bronchospasm, angioedema, hypotension and anaphylactic shock may occur. Allergic reactions such as rash (especially urticaria), conjunctivitis or rhinitis were frequently reported. Local reactions: with extravasation of the drug-pain and inflammatory reactions at the injection site. From the laboratory parameters: very often — an increase in the level of alkaline phosphatase, the activity of” liver ” enzymes, the content of bilirubin, lactate dehydrogenase, hypokalemia, violations of the content of sodium and glucose in the blood serum; often — an increase in the level of creatinine. Other: very often — increased body temperature, increased fatigue, weight gain, taste disorders.

Interaction

No significant changes in the binding of oxaliplatin to plasma proteins in vitro were observed when co-administered with erythromycin, salicylates, granisetron, paclitaxel, and sodium valproate. When interacting with aluminum, it is possible to form a precipitate and reduce the activity of oxaliplatin Pharmacologically incompatible with 0.9% sodium chloride solution and other saline (alkaline) solutions or solutions containing chlorides.

How to take, course of use and dosage

IV drip in the form of 2-6-hour infusions. Oxaliplatin is used only in adults. Hyperhydration is not required when using oxaliplatin. If oxaliplatin is used in combination with 5-fluorouracil, the oxaliplatin infusion should precede the use of 5-fluorouracil. The recommended dose is 85 mg / m2 once every 2 weeks as monotherapy or in combination with 5-fluorouracil. Repeated use of oxaliplatin is performed only when the number of neutrophils >1500/µl and platelets > > 50000/µl. Recommendations for adjusting the dose and mode of use of oxaliplatin. In the case of hematological disorders (neutrophil count), with the development of diarrhea of 4 degrees of toxicity (on the WHO scale), neutropenia of 3-4 degrees (neutrophil count 2 in addition to the usual dose reduction of 5-fluorouracil in the case of their combined use. Patients who develop acute laryngopharyngeal paresthesia during infusions or within a few hours after a 2-hour infusion, the next oxaliplatin infusion should be performed within 6 hours. Recommendations for dose adjustment of oxaliplatin in case of neurotoxicity development: – for symptoms of neurotoxicity that cause pain lasting more than 7 days or for paresthesia without functional disorders that persists until the next cycle, the subsequent dose of oxaliplatin should be reduced by 25%. – for paresthesia with functional disorders that persists until the next cycle, oxaliplatin should be discontinued;- if the severity of neurotoxicity symptoms decreases after discontinuation of oxaliplatin, you may consider resuming treatment. With the development of stomatitis and / or mucositis of the 2nd or higher degree of toxicity, treatment with oxaliplatin should be suspended until they stop or reduce the manifestations of toxicity to the 1st degree. Patients with renal insufficiency. There are no data on the use of the drug in patients with severe renal impairment. Due to limited data on the safety and tolerability of the drug in patients with moderate renal impairment, the benefit/risk ratio for the patient should be weighed before using oxaliplatin. Therapy in this category of patients can be started with the recommended dose, under careful monitoring of renal function. In patients with mild renal impairment, no dose adjustment of oxaliplatin is required. Patients with hepatic insufficiency. No dosage adjustment is required in patients with mild or moderate hepatic insufficiency. There are no data on the use of oxaliplatin in patients with severe hepatic impairment. Elderly patients. The safety profile of oxaliplatin as monotherapy or in combination with 5-fluorouracil in patients over 65 years of age is similar to that observed in patients under 65 years of age. Instructions for preparation of the preparation solutionin the preparation and use of Exorum, do not use needles or other equipment containing aluminum.Do not dissolve the lyophilizate and dilute the solution with 0.9% sodium chloride solution and mix it with other salt (alkaline) solutions or solutions containing chlorides. Water for injection or a 5% dextrose solution should be used to dissolve the lyophilizate. At the same time, a sufficient amount of solvent is added to the Exorum bottle to obtain a solution at a concentration of 5 mg / ml. Immediately after the lyophilizate is dissolved, the infusion solution should be prepared. To prepare an infusion solution, the dissolved preparation Exorum is diluted in 250-500 ml of 5% dextrose solution to obtain a concentration of at least 0.2 mg / ml. The solution for infusions is recommended to be used immediately after preparation. The infusion solution remains stable for 24 hours at a temperature of 2 to 8 °C. The solution with signs of precipitation must be destroyed. You can only use a clear solution. Oxaliplatin solution should not be mixed in the same infusion system with other medications, especially 5-fluorouracil and calcium folinate. The drug should not be administered undiluted.

Overdose

Symptoms: more pronounced side effects. Treatment: symptomatic. Careful monitoring of the patient and strict monitoring of hematological parameters are recommended. The antidote to oxaliplatin is unknown.

Storage conditions

Store in a dry place, protected from light, at a temperature not exceeding 25 °C. Infusion solution — during the day, at a temperature of 2-8 °C.

Shelf life

2 years

Active ingredient

Oxaliplatin

Conditions of release from pharmacies

By prescription

Dosage form

solution for infusions

Purpose

For adults as directed by your doctor

Indications

Cancer