Plaxat lyophilizate 100mg vial, 1pc

Composition

1 bottle contains:

Active ingredients:

oxaliplatin 100 mg.

Auxiliary substances:

lactose monohydrate.

In a bottle of 100 mg of lyophilizate.

In a cardboard box 1 bottle.

Pharmacological action

Pharmacodynamics

The antitumor drug belongs to the group of alkylating agents, is a platinum derivative in which the platinum atom forms a complex with oxalate and 1,2 – diaminocyclohexane. Plaxat has a wide spectrum of cytotoxic action. It is 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 oxaliplatin derivatives interact with DNA by forming inter-and interstitial bridges and inhibit DNA synthesis, which leads to cytotoxicity and determines the antitumor effect.

Pharmacokinetics

Distribution and metabolism

In vivo oxaliplatin undergoes active biotransformation and is not detected in plasma by the end of 2-hour use of the drug at a dose of 85 mg / m2, while 5% 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.

Deduction

By day 5, about 54% of the total dose is detected in the urine and less than 3% in the feces.

Pharmacokinetics in special clinical cases

In patients with renal insufficiency, there is a significant decrease in the clearance of oxaliplatin 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 been studied.

Indications

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

Use during pregnancy and lactation

The drug is contraindicated for use during pregnancy and lactation (breastfeeding).

Women and men of childbearing age should use reliable methods of contraception when using the drug.

Contraindications

• Myelosuppression (number of neutrophils < 2000/µl and/or platelets < 100 000/µl) prior to the first course of treatment;
• peripheral sensory neuropathy with functional impairment prior to first course of treatment;
• marked impairment of renal function (QC less than 30 ml/min);
• pregnancy;
• lactation (breastfeeding);
• hypersensitivity to the components of the drug.

Side effects

The frequency of adverse reactions is presented in accordance with the following gradation:

• very often (>10%);>
• often (>1%, ≤ 10%);>
• sometimes ( > 0,1%, ≤ 1%);>
• rarely ( > 0,01%, ≤ 0,1%);>
• very rare (< 0.01%), including isolated 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 provoked 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 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.

Musculoskeletal disorders. systems: 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.

Dermatological reactions: very often – alopecia, skin rashes; often-peeling of the skin of the palms and feet, erythematous rashes, increased sweating, nail disorders.

From the sensory organs: often-conjunctivitis, visual disturbances; rarely-transient decrease in visual acuity, loss of visual fields, hearing loss, neuritis of the auditory nerve.

Allergic reactions: often-rash (especially urticaria), conjunctivitis or rhinitis; rarely (when used as monotherapy) or often (in combination with 5-fluorouracil +/- calcium folinate) – bronchospasm, angioedema, hypotension and anaphylactic shock.

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, increased activity of liver enzymes, bilirubin, LDH, 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

No significant changes in the binding of oxaliplatin to plasma proteins were observed when co-administered with erythromycin, salicylates, granisetron, paclitaxel, and sodium valproate.

Pharmaceutical interaction

The drug is incompatible with 0.9% sodium chloride solution and other saline (alkaline) solutions or solutions containing chlorides.

When interacting with aluminum, precipitation may form and oxaliplatin activity may decrease

How to take, course of use and dosage

Plaxat is used only in adults. The drug is administered intravenously in the form of 2-6 infusions lasting 1 h. Hyperhydration is not required when using Plaxat. If the drug is used in combination with 5-fluorouracil, the infusion of Plaxate should precede the introduction of 5-fluorouracil.

The recommended dose of Plaxat is 85 mg / m2 once every 2 weeks as monotherapy or in combination with 5-fluorouracil.

Repeated use of Plaxat is performed only when the number of neutrophils > 1500/µl and platelets > > 50 000/µl.

Recommendations for dose adjustment of the Plaxat use regimen

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 the infusion or within a few hours after the 2-hour infusion, the next infusion of Plaxat should be performed within 6 hours.

Recommendations for adjusting the dose of Plaxat in case of neurotoxicity: if symptoms of neurotoxicity are accompanied by pain lasting more than 7 days, or if paresthesia without functional disorders persists until the next cycle, the subsequent dose of Plaxat should be reduced by 25%; if paresthesia with functional disorders persists until the next cycle, Plaxat should be discontinued; if the severity of symptoms of neurotoxicity decreases after discontinuation of Plaxat, you can consider resuming treatment.

With the development of stomatitis and / or mucositis of 2 or more degrees of toxicity, treatment with Plaxat should be suspended until they stop or reduce the manifestations of toxicity to 1 degree.

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 patient benefit/risk ratio should be determined before using Plaxat. 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 Plaxat is required.

No dose adjustment is required in patients with mild or moderate hepatic insufficiency. There are no data on the use of Plaxat in patients with severe hepatic impairment.

Safety profile of Plaxat as monotherapy or in combination with 5-fluorouracil in elderly patients (over 65 years of age) It is similar to that observed in patients under 65 years of age.

Rules for preparing an infusion solution

Do not use needles or other equipment containing aluminum when preparing or injecting Plaxate.

Do not dissolve or dilute the preparation with 0.9% sodium chloride solution or mix it with other saline (alkaline) solutions or solutions containing chlorides.

Water for injection or a 5% dextrose solution should be used to dissolve the lyophilizate. In this case,10 ml of solvent is added to a bottle containing 50 mg of Plaxat, and 20 ml is added to a bottle containing 100 mg 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 the infusion solution, the dissolved drug Plaxat is diluted in 250-500 ml of 5% dextrose solution to obtain a concentration of at least 0.2 mg / ml. The infusion solution for infusions is recommended to be used immediately after preparation; its stability is maintained 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: you can expect more pronounced side effects.

Treatment: careful monitoring of hematological parameters and symptomatic therapy is recommended. There is no specific antidote.

Special instructions

Plaxat should only be used in specialized oncology departments and under the supervision of a qualified oncologist. Constant monitoring of toxic effects during treatment with Plaxat is mandatory.

Regularly (1 time/week), as well as before each use of Plaxat, an analysis of the formed elements of peripheral blood and monitoring of kidney and liver function indicators should be carried out.

Before starting each cycle of therapy with Plaxat, 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 therapy scheme.

If respiratory symptoms appear (dry cough, dyspnoea, wheezing, or detection of pulmonary infiltrates during X-ray examination), treatment with Plaxat 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 Plaxat 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 Plaxat, the infusion should be stopped immediately and appropriate symptomatic treatment should be prescribed. Further use of Plaxat in case of allergic reactions is contraindicated.

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.

When using Plaxat, the precautions taken for the use of cytotoxic drugs should be observed. If lyophilizate or Plaxat solution gets on the skin or mucous membranes, they should be immediately and thoroughly rinsed with water.

Form of production

Lyophilizate for preparation of solution for infusions.

Storage conditions

In a dark place, at a temperature not exceeding 25 °C

Shelf

life 1.5 years

Active ingredient

Oxaliplatin

Conditions of release from pharmacies

By prescription

Dosage form

infusion solution