Description
Latin name
PLAKSAT
Release form
Lyophilisate for solution for infusion.
Packing
In a bottle of 100 mg of lyophilisate. In a cardboard box 1 bottle.
Pharmacological action
Pharmacodynamics
The antitumor drug, which 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. Poster has a wide spectrum of cytotoxic effects. 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.
A study of the mechanism of action of oxaliplatin confirms the hypothesis that derivatives of oxaliplatin interacting with DNA by forming inter- and intra-traction bridges inhibit DNA synthesis, which leads to cytotoxicity and determines the antitumor effect.
Pharmacokinetics
Distribution and metabolism of
In vivo, oxaliplatin undergoes active biotransformation and is not detected in plasma by the end of the 2-hour administration of the drug at a dose of 85 mg / m2, with 5% of the administered platinum being in the blood and the remaining 85% are rapidly distributed tissues or excreted in the urine. Platinum binds to plasma albumin and is excreted in the urine during the first 48 hours.
Excretion of
By day 5, about 54% of the total dose is found in urine and less than 3% in feces.
Pharmacokinetics in special clinical cases
In renal failure, there is a significant decrease in oxaliplatin clearance 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 combination therapy in combination with fluoropyrimidines).
Contraindications
Myelosuppression (neutrophil count <2000 / μl and / or platelet count < 100 000 / μl) before the start of the first course of treatment peripheral sensory neuropathy with functional impairments before the start of the first course of treatment severe impaired renal function (CC less than 30 ml / min) pregnancy lactation (breastfeeding) hypersensitivity to the drug . Use during pregnancy and lactation The drug is contraindicated in pregnancy and lactation (breastfeeding). Women and men of childbearing age should use reliable methods of contraception while using the drug. Composition 1 vial contains: Active substances: oxaliplatin 100 mg. Excipients: lactose monohydrate. Dosage and administration of posterior are used only in adults. The drug is administered intravenously in the form of 2-6 infusions of 1 hour duration. Hyperhydration with the use of Plaxat is not required. If the drug is used in combination with 5-fluorouracil, then the infusion of Plaxat 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 administration of Plaxat is performed only with neutrophils> 1500 / μl and platelets> 50 000 / μl.
Recommendations for dose adjustment of the administration regimen for placard
In case of hematological abnormalities (neutrophil count <1500 / μl and / or platelet count <50 000 / μl), the next course is delayed until the laboratory parameters are restored. 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 3-4 degrees (platelet count <50 000 / μl), the dose of Plaxat should be reduced from 85 doses mg / m2 to 65 mg / m2 in addition to the usual dose reduction of 5-fluorouracil in the case of combination therapy. For patients who develop an acute laryngeopharyngeal paresthesia during the infusion or within a few hours after a 2-hour infusion, the next infusion of Plaxat should be given within 6 hours. Recommendations for adjusting the dose of Plaxat for the development of neurotoxicity: for symptoms of neurotoxicity accompanied by pain lasting more than 7 days, or for paresthesia without functional impairment that persists until the next cycle, the subsequent dose of Plaxat should be reduced by 25% for paresthesia with functional impairment that persists until the next cycle, placard should be abolished with a decrease in the severity of symptoms of neurotoxicity after discontinuation of the placenta, you can consider resuming treatment. With the development of stomatitis and / or mucositis of degree 2 or more toxicity, treatment with Plaksat should be suspended until they are stopped or symptoms of toxicity are reduced to degree 1. There are no data on the use of the drug in patients with severe impaired renal function. Due to the limited data regarding the safety and tolerability of the drug in patients with moderate impaired renal function, the benefit / risk ratio for the patient should be determined before using Plaxat. Therapy in this category of patients can be started with the recommended dose under close monitoring of renal function. With a mild degree of impaired renal function, dose adjustment of Plaksat is not required. In patients with mild to moderate hepatic insufficiency, dose adjustment is not required. Dan With a mild degree of impaired renal function, dose adjustment of Plaksat is not required. In patients with mild to moderate hepatic insufficiency, dose adjustment is not required. Dan With a mild degree of impaired renal function, dose adjustment of Plaksat is not required. In patients with mild to moderate hepatic insufficiency, dose adjustment is not required. DanThere are no data on the use of Plaksat in patients with severely impaired liver function. The safety profile of Plaxat as a monotherapy or when combined with 5-fluorouracil in elderly patients (over 65 years old) is similar to that observed in patients under 65 years of age. Rules for the preparation of the infusion solution. For preparation and administration of Plaxat, needles and other equipment containing aluminum must not be used. Do not dissolve or dilute the preparation with 0.9% sodium chloride solution and do not mix with other saline (alkaline) solutions or solutions containing chlorides. To dissolve the lyophilisate, use water for injection or a 5% dextrose solution. In this case, 10 ml of the solvent is added to the bottle containing 50 mg of the drug Plaxat, and to the bottle, containing 100 mg – 20 ml to obtain a solution at a concentration of 5 mg / ml. Immediately after dissolving the lyophilisate, proceed with the preparation of a solution for infusion. To prepare the infusion solution, the dissolved preparation Plaxat is diluted in 250-500 ml of a 5% dextrose solution to obtain a concentration of at least 0.2 mg / ml. The infusion solution for infusion is recommended to be used immediately after preparation, its stability is maintained for 24 hours at a temperature of 2 ° to 8 ° C. A solution with signs of precipitation must be destroyed. You can use only a clear solution. Oxaliplatin solution should not be mixed in the same infusion system with other drugs, especially 5-fluorouracil and calcium folinate. The drug cannot be administered undiluted. 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 single messages.
From the hemopoietic system: very often – anemia, leukopenia, neutropenia, thrombocytopenia, lymphopenia often – febrile neutropenia (including grade 3-4), sepsis with 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 side of the central nervous system and peripheral nervous system: very often – peripheral neurosensory neuropathy, sensory disturbances, headache, asthenia often – dizziness, meningism, depression, insomnia sometimes – increased nervousness rarely – dysarthria.
Neurotoxicity is a dose-limiting side effect. Often, symptoms of sensory neuropathy are triggered by a cold. The duration of these symptoms, which usually stop between the courses, increases depending on the total dose of oxaliplatin. Functional disorders, which are expressed by the difficulty in 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% in the case of a total dose of 1020 mg / m2 (12 cycles). In most cases, neurological symptoms improve or completely disappear after discontinuation of treatment. However, in 3% of patients, 3 years after the end of treatment, either stable localized paresthesia of moderate intensity (2.3%) or paresthesia affecting functional activity (0.5%) was observed.
Acute neurosensory manifestations were noted during treatment with oxaliplatin, which usually occurred within a few hours after drug administration and were most often triggered by cold. They were characterized by transient paresthesia, dysesthesia or hypesthesia, rarely (1-2%) with acute laryngeopharyngeal 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). Also observed were phenomena such as jaw spasm, tongue dysesthesia, dysarthria and a feeling of pressure in the chest. Typically, these symptoms quickly stopped both without the use of drug therapy, and with the introduction of antihistamines and bronchodilators. An increase in the infusion time during subsequent cycles of oxaliplatin therapy can reduce the frequency of this syndrome.
From the musculoskeletal side. systems: very often – back pain often – arthralgia, bone pain.
From the respiratory system: very often – cough, shortness of breath often – rhinitis, infections of the upper respiratory tract rarely – pulmonary fibrosis.
From the cardiovascular system: often – pain behind the sternum, deep vein thrombophlebitis, pulmonary thromboembolism.
From the urinary system: often – hematuria, dysuria.
Dermatological reactions: very often – alopecia, skin rashes often – peeling of the skin of the hands and feet, erythematous rashes, excessive sweating, irregularities on the part of the nails.
On the part of the sensory organs: often – conjunctivitis, visual impairment rarely – transient decrease in visual acuity, loss of visual fields, hearing loss, auditory nerve neuritis.
Allergic reactions: often a rash (especially urticaria), conjunctivitis or rhinitis rarely (when used as monotherapy) or often (in combination with 5-fluorouracil +/- calcium folinate) – bronchospasm, angioedema, arterial hypotension and anaphylactic shock.
Local reactions: with extravasation of the drug, pain and inflammatory reactions at the injection site.
On the part of laboratory indicators: very often – an increase in the level of alkaline phosphatase, an increase in the activity of liver enzymes, the content of bilirubin, LDH, hypokalemia, violations of the content of sodium and glucose in the blood serum is often an increase in creatinine.
Others: very often – increased body temperature, increased fatigue, increased body weight, taste disturbances.
No drug interaction of
There was no significant change in the binding of oxaliplatin to blood plasma proteins 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.
In the interaction with aluminum, sedimentation and oxaliplatin activity decrease
Overdose
Symptoms: more pronounced side effects can be expected.
Treatment: careful monitoring of hematological parameters, carrying out symptomatic therapy is recommended. There is no specific antidote.
Storage conditions
Keep out of the reach of children, protected from light, at a temperature not exceeding 25 ° C.
Expiration 1.5 years.
Deystvuyuschee substances
oxaliplatin
Dosage form
dosage form
solution for infusion
Actavis Italy SpA, Switzerland
