Oxaliplatin medac lyophilisate solution for infusion 50mg vials, 1pc

Composition

1 bottle contains:

Active ingredients:

oxaliplatin 50 mg.

Auxiliary substances:

lactose monohydrate.

In a bottle of 50 mg of lyophilizate.

In a cardboard box 1 bottle.

Pharmacological action

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.

Pharmacokinetics

In vivo oxaliplatin undergoes active biotransformation and is not detected in plasma by the end of 2 hours after use at a dose of 130 mg / sq. m, while 15% of the administered platinum is in the blood, and the remaining 85% is rapidly distributed to tissues or excreted by the kidneys. Platinum binds to plasma albumin and is excreted in the urine within the first 48 hours.

By day 5, about 54% of the total dose is detected in the urine and less than 3% in the feces. In patients with renal insufficiency, there is a significant decrease in the clearance of oxaliplatin from 17.6 l/h to 9.95 l/h. The effect of severe renal failure on platinum clearance has not been studied.

Indications

• Adjuvant therapy of stage III colorectal cancer (Duke C) after radical resection of the primary tumor in combination with 5-fluorouracil and folinic acid;
• disseminated colorectal cancer (as monotherapy or combination therapy in combination with 5-fluorouracil and folinic acid).

Use during pregnancy and lactation

It is contraindicated during pregnancy and lactation.

Contraindications

• Hypersensitivity to oxaliplatin or other components of the drug;
• myelosuppression (a neutrophil count less than 2000/µl and/or platelets less than 100,000/µl) prior to the first course of treatment;
• peripheral sensory neuropathy with functional impairment prior to first course of treatment;
• severe renal dysfunction (creatinine clearance less than 30 ml/min);
• pregnancy;
• breast-feeding breast.

Side effects

The most common side effects observed with oxaliplatin, including in combination with 5-fluorouracil / folinic acid, were gastrointestinal reactions (diarrhea, nausea, vomiting, mucositis), hematological reactions (neutropenia, thrombocytopenia) and neurological reactions (acute and cumulative dose-dependent peripheral sensory neuropathy). Overall, these side effects were more frequent and severe when oxaliplatin was combined with 5-fluorouracil / folinic acid, compared to 5-fluorouracil and folinic acid alone.

The frequency of adverse reactions listed below is set out in accordance with the following gradation:

• very common (> 1/10);>
• common ( > 1/100, > < 1/10);
• infrequent ( > 1/1000, >< 1/100);
• rare ( > 1/10000, >< 1/1000);
• very rare (

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, gastro-esophageal reflux, hiccups; infrequently-intestinal obstruction; rarely-colitis, including cases of pseudomembranous colitis.

From the central and peripheral nervous system: very often – peripheral sensorineural neuropathy, sensitivity disorders, headache, asthenia; often-dizziness, meningism, depression, insomnia; infrequently-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 hyposthesia, 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 such phenomena as jaw spasm, tongue dysesthesia, dysarthria and a feeling of pressure in the chest. 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 can reduce 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, bilirubin, lactate dehydrogenase, hypokalemia, violations of sodium and glucose in the blood serum; often-an increase in creatinine.

Other: very often – increased body temperature, increased fatigue, weight gain, taste disorders.

Interaction

Pharmacologically incompatible with alkaline solutions and solutions containing chlorine.

In cases of use of a single dose of 85 mg/m2 of oxaliplatin to patients immediately before the appointment of 5-fluorouracil, there was no change in the level of 5-fluorouracil.

No significant changes in the binding of oxaliplatin to plasma proteins were observed in joint in vitro experiments with erythromycin, salicylates, granisetron, paclitaxel, and sodium valproate.

Incompatibilities

• do not use together with alkaline preparations or solutions (in particular,5-fluorouracil, alkaline solutions, and trometamol drugs vainiunai acid containing trometamol as excipients);
• not to be used for drug dissolution or dilution of the drug solution (for the preparation of infusion solution) salt solutions, do not mix with other drugs in the same container or in the infusion system;
• do not use the equipment for the introduction of aluminum containing (possibly precipitate formation and a decrease in the activity of oxaliplatin).

How to take it, course of use and dosage

Intravenously in the form of 2-6 h infusions. Hyperhydration is not required when using oxaliplatin.

It is used only for adults.

The drug should be used immediately after the preparation of the solution. When combined with 5-fluorouracil, oxaliplatin infusion should precede 5-fluorouracil use.

Adjuvant therapy for colorectal cancer: 85 mg / m once every 2 weeks for 12 cycles (6 months).

Disseminated colorectal cancer: 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 exceeds 1500/µl and platelets exceeds 50,000/µl.

Recommendations for adjusting the dose and mode of use of oxaliplatin.

In case of hematological disorders (neutrophil count < 1500 / µl and / or platelets

With the development of diarrhea of 4 degrees of toxicity (according to the WHO scale), neutropenia of 3-4 degrees (neutrophil count < 1000/µl), thrombocytopenia of 3-4 degrees (platelet count

Patients who develop acute laryngopharyngeal paresthesia during infusions or within a few hours after 2-hour infusions, the next oxaliplatin infusion should be performed within 6 hours.

Recommendations for dose adjustment of oxaliplatin in patients with neurotoxicity:

• when symptoms of neurotoxicity, causing pain, lasting more than 7 days, the subsequent oxaliplatin dose should be reduced from 85 mg/m2 to 65 mg/m 2 in the treatment of metastatic colorectal cancer and up to 75 mg/m 2 in adjuvant therapy;
• if paraesthesia without functional disorders, continuing until the next cycle, the subsequent oxaliplatin dose should be reduced from 85 mg/m 2 to 65; mg/m for the therapy of metastatic colorectal cancer and up to 75 mg/m in adjuvant therapy;
• if paraesthesia with functional impairment, continuing until the next cycle, oxaliplatin should be abolished;
• in the reduction of symptoms of neurotoxicity of oxaliplatin after cancellation, you can 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 oxaliplatin 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 the drug. 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 older than 65 years is similar to that observed in patients under 65 years of age.

Instructions for preparation of the drug solution

When preparing solutions and injecting oxaliplatin, do not use needles or other equipment containing aluminum.

Before use, the drug is dissolved in water for injection or in a 5% dextrose solution, obtaining a solution with a concentration of 5 mg / ml of oxaliplatin (10 ml of solvent is introduced into a 50 mg bottle,20 ml into a 100 mg bottle, and 30 ml of solvent into a 150 mg bottle). The drug recovered in this way is immediately diluted with 250-500 ml of a 5% dextrose solution. The concentration of the resulting oxaliplatin solution should be from 0.2 to 0.7 mg / ml, with 0.7 mg / ml being the highest concentration used in clinical practice at a dose of 85 mg / m2.

Only the recommended solvents should be used to prepare the drug solution.

Do not use the drug undiluted.

Do not use saline solutions (sodium chloride solution) to dissolve the drug or dilute the drug solution (to prepare an infusion solution). Do not mix in the same container, do not prescribe simultaneously in the same infusion system with other drugs (especially with 5-fluorouracil, basic solutions, trometamol and folinic acid preparations containing trometamol in their composition).

Oxaliplatin may be given in conjunction with folinic acid infusions. In this case, the drugs should not be mixed in the same infusion container. Folinic acid for infusions should be diluted using a 5% glucose solution, but in no case should solutions containing sodium chloride or alkaline solutions be used.

The prepared solution of the drug should be transparent and should not contain undissolved particles. Otherwise, the solution of the drug can not be used. The solution of the drug is used immediately after preparation.

The drug is intended for single use only. The unused solution of the drug must be destroyed.

The drug should be administered in the central venous line or in the peripheral vein for 2-6 hours.

In case of extravasation, the drug use should be stopped immediately.

Materials used for the preparation of the solution and its use should be destroyed in accordance with the rules for the use of cytotoxic drugs.

Overdose

Symptoms: an increase in the described side effects. The antidote is not known.

Treatment: hematological control and symptomatic therapy.

Special instructions

Treatment with Oxaliplatin medac should be carried out under the supervision of a doctor who has experience in the use of cytotoxic drugs. Constant monitoring of possible toxic effects during oxaliplatin therapy is mandatory.

Regularly (once a week), as well as before each use of Oxaliplatin medak, it is necessary to monitor the formed elements of peripheral blood and indicators of kidney and liver function.

Before starting each cycle of therapy with Oxaliplatin medac, a neurological examination should be performed to detect signs of neurotoxicity.

Patients should be informed about the possibility of persistent symptoms of peripheral sensory neuropathy after the end of treatment. Localized moderate paresthesias with functional disorders can last up to 3 years after the end of treatment according to the adjuvant drug use scheme.

If symptoms such as dry cough, dyspnoea, wheezing or detection of pulmonary infiltrates during X-ray examination appear, treatment with Oxliplatin medak should be suspended until the presence of interstitial pneumonitis is excluded.

Symptoms such as dehydration, paralytic ileus, intestinal obstruction, hypokalemia, metabolic acidosis, and renal failure may be due to severe diarrhea or vomiting, especially when Oxaliplatin medac is used in combination with 5-fluorouracil.

Patients with a history of allergic reactions to other platinum compounds should be monitored for allergic symptoms. In the event of an anaphylactic-like reaction to oxaliplatin, the infusion should be stopped immediately and appropriate symptomatic treatment should be prescribed. Further use of Oxaliplatin medak in case of allergic reactions is contraindicated. If liver function disorders or portal hypertension occur that are not caused by liver metastases, consideration should be given to the possible presence of drug-induced hepatovascular disorders, which are very rare.

In case of extravasation, the infusion should be stopped immediately and local symptomatic treatment should be initiated. The remaining dose of the drug should be injected into another vein. Women and men should use reliable methods of contraception during treatment and for 6 months after the end of oxaliplatin therapy. When using Oxaliplatin medac, all the usual instructions for the use of cytotoxic drugs must be followed. If the lyophilizate or Oxaliplatin medac solution gets on the skin or mucous membranes, they should be immediately and thoroughly rinsed with water.

Influence on the ability to drive vehicles and other mechanisms that require increased concentration of attention

Not studied. However, the use of oxaliplatin increases the risk of dizziness, nausea, vomiting, and other neurological symptoms that affect the speed and adequacy of the reaction and, thus, reduce the ability to drive a car and use mechanisms.

Form of production

Lyophilizate for infusion solution preparation

Storage conditions

Keep out of the reach of children and out of the reach of light at a temperature not exceeding 25 °C.

Shelf

life is 2.5 years.

Active ingredient

Oxaliplatin

Conditions of release from pharmacies

By prescription

Dosage form

infusion solution