Universal reference book for medicines
Product name: ADCETRIS ® (ADCETRIS ® )

Active substance: brentuximab vedotin

Type: Antitumor drug.
Monoclonal antibodies
Manufacturer: TAKEDA PHARMA (Denmark) manufactured by BSP PHARMACEUTICALS (Italy), which issues quality control TAKEDA ITALIA (Italy)
Composition, form of production and packaging
Lyophilizate for the preparation of concentrate for the preparation of a solution for infusions in the form of a mass or powder of white or almost white color; reconstituted solution - colorless, transparent or slightly opalescent.
1 f.
Brentuksimab Vedotin * 50 mg **
* Conjugate consisting of a CD30-directed monoclonal antibody (cAC10) covalently bound to monomethylaurethane E (MMAE) (SGD-1006);
** The amount of brutuksimab vedotin, including an excess of 10%, is 55 mg; After reconstitution, each ml of the solution contains 5 mg of brentuksimab vedotin.
Excipients: citric acid monohydrate - 2.1 mg, sodium citrate dihydrate - 56.1 mg,?,? - trehalose dihydrate - 700 mg, polysorbate 80 - 2 mg.
Vials of transparent glass type I (1) - packs of cardboard with control of the first opening.
INSTRUCTION FOR THE SPECIALIST.
Description of the drug approved by the manufacturer for the printed edition of 2017.
PHARMACHOLOGIC EFFECT
Antitumor drug. Brentuksimab vedotin is a conjugate of a monoclonal antibody and an antitumor substance that is delivered to tumor cells expressing the CD30 antigen and causes their selective apoptosis. In preclinical studies, it was found that the biological activity of brutuksimab vedotin is the result of a multi-stage process. Binding of the antibody-antitumor conjugate to the CD30 antigen on the cell surface triggers the endocytosis process, which causes the conjugate-CD30 complex to enter the cell and is transported to the lysosomes. Within the cell, the active component of MMAE is released as a result of proteolytic cleavage. Binding of MMAE to tubulin results in destruction of the microtubule network within the cell, inhibition of the cell cycle, and, ultimately, death of the CD30-expressing tumor cell.
In patients with classical Hodgkin's lymphoma and systemic anaplastic large cell lymphoma (systemic ACCL), the CD30 antigen is expressed on the surface of tumor cells. This expression does not depend on the stage of the disease, previous therapy and transplantation. Due to the CD30-directed mechanism of action, brentuksimab vedotin is able to overcome chemotherapeutic resistance, since in patients refractory to multicomponent chemotherapy, the antigen CD30 is invariably expressed, regardless of the previous status of transplantation.
Additional mechanisms of antibody exposure, due to their other properties, can not be excluded. CD30-directed mechanism of action of Brentuksimab vedotin, stable expression of CD30 in patients with classical Hodgkin's lymphoma and systemic ACCL, as well as therapeutic application spectra and clinical evidence of the effectiveness of the drug for the treatment of these two CD30-positive tumors, even after several previous lines of therapy, are the biological justification use of this drug in patients with recurrent or refractory Hodgkin's lymphoma and systemic ACCL with and without a previous autologous transplant ntatsii stem cells.
PHARMACOKINETICS
Suction
C max Brentuksimab vedotina, as a rule, was observed at the end of the infusion procedure or at the sampling point closest to the completion of the procedure. A multi-exponential decrease in serum concentrations of brutuksimab vedotin was observed with a finite T 1/2 , approximately equal to 4-6 days. Concentrations were approximately proportional to the administered doses. The minimal cumulation of breccinucimab vedotin or its absence, observed at multiple doses every 3 weeks, is consistent with an estimate of the duration of the final T 1/2 . The typical C max and AUC for brentuksimab vedotin after single administration of the drug at a dose of 1.8 mg / kg, according to the Phase 1 study, were 31.98 μg / ml and 79.41 μg / ml day, respectively.
The main metabolite of brutuksimab vedotin is MMAE. Medians C max , AUC and T max for MMAE after single injection of the drug at a dose of 1.8 mg / kg, according to the data of the Phase 1 study, were 4.97 ng / ml, 37.03 ng / ml day and 2.09 days, respectively.
The level of MMAE decreased after multiple doses of Brentuksimab vedotin, and was approximately 50-80% of the level of the first dose.
In the first cycle, the increased level of MMAE correlated with an absolute decrease in the number of neutrophils.
Distribution
In in vitro studies, the level of binding of MMAE to human plasma proteins ranged from 68 to 82%. It is not assumed that MMAE will displace other substances or will be replaced by drugs with a high degree of binding to plasma proteins. In in vitro studies, MMAE was a substrate of the P-glycoprotein and did not inhibit it in clinical concentrations.
In humans, the average V d at an equilibrium concentration of the drug is 6-10 liters. Based on the population pharmacokinetic analysis data, the typical apparent V d (V d of the VM metabolite or V d in the peripheral compartment of the VMP) of MMAE was 7.37 L and 36. 4 L, respectively.
Metabolism
It is assumed that Brentuksimab Vedotin is catabolized as a protein with recyclization or excretion of the amino acid component.
Data from in vivo studies conducted on animals or involving humans suggest that only a small fraction of MMAE released from brutuksimab vedotin is metabolized. The levels of MMAE metabolites in human plasma were not measured. At least one MMAE metabolite showed in vitro activity.
MMAE is the substrate of CYP3A4 and, possibly, CYP2D6. In vitro studies indicate that the metabolism of MMAE predominantly proceeds by oxidation via CYP3A4 / 5. In vitro studies using human liver microsomes, it has been shown that MMAE has an inhibitory effect on CYP3A4 / 5 only at concentrations well above the concentrations permitted for clinical use. MMAE does not inhibit other isoforms.
MMAE did not activate any of the major CYP450 enzymes in primary cultures of human hepatocytes.
Excretion
Brutuksimab vedotin is removed by catabolism with characteristic clearance and T 1/2 , equal to 1.457 l / day and 4-6 days, respectively.
The excretion of MMAE was limited by the rate of its release from the conjugate to the monoclonal antibody, the characteristic clearance and T 1/2 MMAE were 19.99 l / day and 3-4 days, respectively.
The excretion study was conducted with the participation of patients who received brentuksimab vedotin at a dose of 1.8 mg / kg. Approximately 24% of the total MMAE administered as part of the conjugate with the monoclonal antibody during the infusion of brutuksimab vedotin was detected in urine and feces for 1 week. Of this amount, approximately 72% was found in the stool. A smaller amount of MMAE (28%) was excreted by the kidneys.
Pharmacokinetics in special clinical cases
Population pharmacokinetic analysis showed that the initial concentration of serum albumins significantly influences the clearance of MMAE. The analysis showed that in patients with low serum albumin concentrations (<3.0 g / dL), the MMAE clearance was 2-fold lower, compared to patients with normal serum albumin concentrations.
Liver failure. The pharmacokinetics of the drug and MMAE after administration of 1.2 mg / kg of the drug to patients with weak (Child-Pugh class A; n = 1), medium (Child-Pugh class B; n = 5) and severe (Child-Pugh class C; n = 1) the degree of hepatic insufficiency. In comparison with patients with normal hepatic function, in patients with hepatic insufficiency, MMAE excretion increased approximately 2.3-fold.
Renal failure. The pharmacokinetics of the drug and MMAE after administration of the drug at a dose of 1.2 mg / kg to patients with mild (n = 4), moderate (n = 3) and severe (n = 3) degrees of renal insufficiency were investigated. In comparison with patients with normal renal function, in patients with severe renal failure, excretion of MMAE increased approximately 1.9-fold.
Patients of advanced age. Clinical studies of brutuksimab vedotin did not include a sufficient number of patients older than 65 years. Thus, at the present time it is impossible to establish whether the response to treatment varies between elderly and young patients.
Children's population. Clinical studies of brutuksimab vedotin did not include sufficient numbers of patients younger than 18 years of age. Thus, at the present time it is impossible to establish whether the pharmacokinetics in this category of patients differ from adult patients.
INDICATIONS
- treatment of patients with recurrent / refractory CD30 + Hodgkin's lymphoma after autologous stem cell transplantation or after a minimum of two lines of previous therapy, when autologous stem cell transplantation or combined chemotherapy is not considered a treatment option;
- treatment of patients with recurrent / refractory ACC.
DOSING MODE
Enter in / in the form of infusions.
Treatment with the drug should be carried out under the supervision of a doctor who has experience in the use of antitumor drugs. Before each dose administration, a clinical blood test should be performed. Patients should be under strict supervision during and after infusion.
The recommended dose is 1.8 mg / kg as an IV infusion for 30 minutes every 3 weeks.
If the patient's body weight exceeds 100 kg, a weight value of 100 kg should be used when calculating the dose.
For patients with severe renal insufficiency, the recommended initial dose is 1.2 mg / kg IV infusion over 30 min every 3 weeks. Patients with renal insufficiency should be under strict supervision.
For patients with hepatic insufficiency, the recommended initial dose is 1.2 mg / kg IV infusion for 30 minutes every 3 weeks. Patients with hepatic insufficiency should be under strict supervision.
The safety and efficacy of the drug in elderly patients (65 years and older) have not been established; no data.
Safety and effectiveness of the drug in children and adolescents under the age of 18 years are not established; no data.
Duration of therapy
When a stable condition is reached or if the disease progression is positive, the patient must undergo at least 8, but not more than 16 treatment cycles (approximately 1 year).
Calculation of dose
Calculation of the total volume (ml) of the drug solution for further dilution:
Total dose of the preparation (ml) for further dilution = Dose of the preparation (mg / kg)? Body weight of the patient (kg) / concentration of the solution reconstituted in the vial (5 mg / ml)
Calculation of the required number of vials of the drug:
The required number of vials = Total dose of the drug (ml) for administration / Total volume in one vial (10 ml / vial)
Table 1. Examples of calculations for patients with body weight from 60 kg to 120 kg. The recommended dose of the drug is 1.8 mg / kg
Body weight of the patient (kg) Total dose = body weight of the patient? recommended dose [1.8 mg / kg a ] Total volume for dilution b = total dose / concentration of solution reconstituted in vial [5 mg / ml] Required number of vials = total volume for dilution / total volume in one vial [10 ml / vial]
60 kg 108 mg 21.6 ml 2.16 bottles
80 kg 144 mg 28.8 ml 2.88 bottles
100 kg 180 mg 36 ml 3.6 bottles
120 kg in 180 mg g 36 ml 3.6 bottles
a In the case of a reduced dose, 1.2 mg / kg is used in the calculations.
b For dilution in 150 ml of solution and introduction by iv infusion for 30 min every 3 weeks.
c If the patient's body weight exceeds 100 kg, a weight value of 100 kg should be used when calculating the dose.
g The maximum recommended dose is 180 mg.
Correction of dose
Neutropenia
If neutropenia is detected during treatment, interval between doses should be increased to control it. The corresponding recommendations on the dosage regimen are given in Table 2.
Table 2. Recommendations for the dosing regimen for neutropenia
Severity of neutropenia (signs and symptoms [short description of STAAE]) Change in dosing regimen
Degree 1 (<lower limit of the norm is 1500 / mm 3 <lower limit of the norm is 1.5 × 10 9 / l) or Degree 2 (<1500-1000 / mm 3 <1.5-1.0 × 10 9 / L) Continue treatment according to the previous scheme and the same dose
Degree 3 (<1000-500 / mm 3 <1.0 -0.5 × 10 9 / L) or Degree 4 (<500 / mm 3 <0.5 × 10 9 / L) Stop treatment until neutropenia severity returns to grade 2 or baseline level, then continue treatment according to the previous scheme and with the same dose. With the development of grade 3 or 4 neutropenia, additional assignment of recombinant hematopoietic factors of G-CSF or GM-CSF
a The classification is based on the "General Terminology of Criteria for Adverse Reactions" (CACAE) c. 3.0 National Cancer Institute (NCI).
b With the development of lymphopenia of 3 and 4 degrees of severity, patients can continue treatment without changes.
Peripheral Neuropathy
If peripheral sensory or motor neuropathy occurs or aggravates during the treatment period, the following recommendations for the dosing regimen should be followed (Table 3).
Table 3. Recommendations for dosing regimens for newly diagnosed or progressing sensory or motor neuropathies
Degree of severity of progressive sensory or motor neuropathy (signs and symptoms [short description of STAAE]) Change in dosing regimen
Degree 1 (paresthesia and / or prolapse of reflexes, without loss of functionality) Continue treatment with the same regimen at the same dose
Degree 2 (impaired functionality but without obvious effect on daily activity) Degree 3 (difficulty daily activity) Stop treatment until the degree of severity of neuropathy returns to grade 1 or baseline, then restart treatment using a reduced dose of 1.2 mg / kg every 3 weeks
Degree 4 (sensory neuropathy leading to disability, or motor neuropathy, life-threatening or leading to paralysis) Discontinue treatment


a The classification is based on the "General Terminology of Criteria for Adverse Reactions" (CACAE) c. 3.0 National Cancer Institute (NCI).
Preparation of the infusion solution
During the use of the drug, aseptic conditions must be observed.
Instructions for preparing a reconstituted solution
1. The contents of a single vial for single use must be dissolved in 10.5 ml of sterile water for injection in order to obtain a solution of 11 ml (including dissolved solids) with a final concentration of 5 mg / ml of Brentuksimab vedotin. Direct the jet along the wall of the vial. Do not direct the jet directly onto the lyophilized mass or powder.
2. Carefully turn the vial to facilitate dissolution. DO NOT BURST.
3. The solution reconstituted in the vial should be clear or slightly opalescent, colorless. The final pH should be 6.6.
4. The reconstituted solution must be inspected for any foreign mechanical inclusions and / or discoloration. In case of detection of foreign mechanical inclusions and / or discoloration, the solution must be destroyed.
Instructions for preparing a solution for administration
The required amount of the reconstituted solution of the drug should be removed from the vial (s) and added to the infusion set with a minimum volume of 100 ml containing a solution of sodium chloride for injection of 9 mg / ml (0.9%) in order to obtain a final drug concentration of 0.4-1.8 mg / ml . The reconstituted solution can also be diluted with a 5% glucose solution for injection or Ringer's lactate injection.
Gently invert the bag to mix the drug solution. Do not shake.
Do not add other medications to the prepared infusion solution or intravenous infusion system. The infusion system must be washed with a solution of sodium chloride for injection 9 mg / ml (0.9%), or with a 5% glucose solution for injection or Ringer's lactate injection.
Infusion with the drug is carried out immediately after the preparation of the solution.
The total storage time of the solution from the moment of dissolution to the infusion of the patient should not exceed 24 hours at a temperature of 2 ° to 8 ° C, the preparation does not contain preservatives.
Mode of application
The recommended dose of the drug is administered as an intravenous infusion for 30 minutes.
It is not allowed to inject the drug solution with IV bolus or bolus injection. The solution of the drug should be administered through a separate intravenous catheter, while it should not be mixed with other drugs. Treatment should be discontinued in the event of progression of the disease or undesirable toxicity.
SIDE EFFECT
Adverse reactions to the drug are ordered according to the system-organ class and are consistent with the terms of preferred use (in accordance with MedDRA) (Table 4). Determination of the frequency of adverse reactions: very often (? 1/10), often (? 1/100 to <1/10), infrequently (? 1/1000 to <1/100), rarely (? 10 000 to <1/1000 ), very rarely (<1/10 000), the frequency is unknown (can not be calculated on the basis of available data).
Table 4. Adverse reactions recorded after application of the drug
Frequency Adverse Reactions
Infectious and parasitic diseases
Very often Infection a
Often, sepsis / septic shock, upper respiratory tract infection, herpes zoster, pneumonia
is not often Thrush, Pneumonia, staphylococcal bacteremia
incidence is unknown Progressive multifocal leukoencephalopathy
Hematopoietic system
Very often Neutropenia
is often anemia, thrombocytopenia,
frequency unknown Febrile neutropenia
Immune system
Frequency unknown anaphylactic reaction
metabolism
Most Hyperglycemia
Uncommon tumor lysis syndrome
Over one hundred Rhone nervous system
Very often, peripheral sensory neuropathy
Often, peripheral motor neuropathy, dizziness, demyelinating polyneuropathy
The respiratory system
is often cough, shortness of breath
Digestive System
Very often, diarrhea, nausea, vomiting,
frequent constipation, elevated ALT / AST
Uncommon Acute pancreatitis
Skin and subcutaneous tissue
Very often, alopecia, pruritus
often the rash
Uncommon Stevens-Johnson syndrome, toxic epidermal necrolysis
the part of the musculoskeletal system
is often Myalgia
often arthralgia, back pain
General reactions
Very often Ut yaemost, fever, infusion reactions used
often chills
andPreferred use of the terms that are registered in the class "Infectious and parasitic diseases" include sepsis / septic shock, upper respiratory infection, pneumonia, and herpes zoster.
b terms of preferred use related to "Infusion reactions" class are chills (4%), nausea, dyspnea, pruritus (3%) and cough (2%).
Description of individual adverse events
Adverse reactions as a result of which it was decided to delay the next infusion for up to 3 weeks, which were reported by more than 5% of patients: neutropenia (14%) and peripheral sensory neuropathy (11%).
Adverse reactions, as a result of which it was decided to reduce the doses, and that have been recorded more than 5% of patients: peripheral sensory neuropathy (8%). In 90% of patients in the Phase 2 study dose was maintained throughout the treatment at the recommended level of 1.8 mg / kg.
In the treatment of brentuximab vedotin may develop severe and prolonged (? 1 week), neutropenia, and this may increase the risk of severe infections. The average duration of neutropenia, 3 or 4 severity was limited (1 week) 2% of patients had grade 4 neutropenia gravity lasted? 7 days.
Less than half of the patients Phase 2 3 or 4 neutropenia severity was the cause of the temporal development of infection, most patients with neutropenia associated infections have 1 or 2 degrees.
Among patients with peripheral neuropathy mean follow-up of the treatment to the last assessment was approximately 10 weeks. At the time of the last assessment, 62% of the 84 patients with peripheral neuropathy was noted the disappearance or alleviation of the symptoms of peripheral neuropathy. The average duration of the period from the beginning to the resolution or relief of symptoms for all adverse events was 6.6 weeks (range, 0.3 weeks, 54.4 weeks).
Cases of progressive multifocal leukoencephalopathy is the basic clinical research Phase 2 have been reported.
Cases of acute pancreatitis (including fatal) is the base phase 2 clinical studies were reported. It is necessary to consider the diagnosis of acute pancreatitis when first introduced or increasing abdominal pain. Cases of anaphylaxis, registered outside the basic clinical research Phase 2 are discussed in the section. The symptoms of anaphylaxis, among others, may include urticaria, angioneurotic edema, hypotension and bronchospasm.
Cases of febrile neutropenia is the basic clinical research Phase 2 have been reported. Febrile neutropenia was observed 5 severity of the patient included in the phase 1 studies with increasing dose after a single dose 3.6 mg / kg brentuximab vedotin.
Hepatotoxicity
in patients treated with brentuximab vedotin, have been reported cases of hepatotoxicity, especially in asymptomatic infection, mild to moderate transient increase in ALT activity / ACT.
immunogenicity
In two studies, phase 2 in patients with relapsed or refractory Hodgkin lymphoma or systemic ALCL determined brentuximab vedotin antibody every 3 weeks, using sensitive electrochemiluminescence immunoassay. Approximately 35% of patients who participated in these studies revealed the presence of antibodies to brentuximab vedotin. Most of them have a positive result was observed before the second dose, and 7% were permanently ATA-positive (antiterapevticheskie antibodies), and 62% of the ATA-positive patients attended neutralizing antibodies. 1% of patients experienced adverse reactions related to the infusion, which have led to discontinuation of treatment.
The appearance of antibodies to brentuximab vedotin not correlated with clinically significant decrease brentuximab vedotin concentration in blood plasma, and did not lead to decrease in efficiency brentuximab vedotin. The appearance of antibodies to brentuximab vedotin not necessarily lead to the development of infusion reactions. The frequency of infusion reactions was higher in the group constantly ATA-positive patients (30%) compared with the group temporarily ATA-positive patients (12%) and a group of patients who had undetectable ATA (7%).
The patient should be informed of the need to inform your doctor about all the cases of adverse reactions, including not listed in the instructions for medical use.
CONTRAINDICATIONS
- hypersensitivity to any component of the drug;
- combined use with bleomycin brentuximab vedotin due to the occurrence of pulmonary toxicity;
- Pregnancy;
- the period of breast-feeding;
- Children up to age 18 years (effectiveness and safety have not been proved).
PREGNANCY AND LACTATION
Women of childbearing age should be warned about the need to prevent pregnancy during treatment brentuximab vedotin, and must use two methods of effective contraception during the period of application of brentuximab vedotin, and for 6 months after treatment. In case of pregnancy during treatment with brentuximab vedotin, the patient should be informed of the potential threat to the fetus.
Data concerning the use of brentuximab vedotin in pregnant women are not available. Use of the drug during pregnancy is contraindicated.
No data on the excretion of the drug or its metabolites in breast milk. Risk to the infant can not be excluded. The use of the drug in the period of breastfeeding is contraindicated.
Men's fertility
is not known whether the use of the drug has an effect on human spermatogenesis. Preclinical studies have demonstrated that testicular toxicity, which can cause changes in male fertility. The presence aneugennyh effects from MMAE. Men planning brentuximab vedotin treatment is recommended before starting therapy to deposit sperm samples. Men undergoing treatment brentuximab vedotin, and for 6 months after the last dose of the drug, it is recommended to use an appropriate method of barrier contraception, and it is not recommended to plan the conception of a child.
APPLICATION FOR FUNCTIONS OF THE LIVER
For patients with severe renal insufficiency, the recommended initial dose of 1.2 mg / kg / infusion in a form for 30 minutes every 3 weeks. Patients with renal insufficiency should be under strict supervision.
APPLICATION FOR VIOLATIONS OF THE FUNCTION OF KIDNEYS
For patients with hepatic insufficiency recommended starting dose is 1.2 mg / kg / in in the form of infusion over 30 minutes every 3 weeks. Patients with hepatic insufficiency should be under strict supervision.
APPLICATION IN ELDERLY PATIENTS
The safety and efficacy of the drug in elderly patients (65 years and older) have not been established; data are not available.
SPECIAL INSTRUCTIONS
Progressive multifocal leukoencephalopathy
In patients treated with brentuximab vedotin may occur reactivation of the virus, John Cunningham (JC-virus), leading to the development of progressive multifocal leukoencephalopathy (PML) and death. Cases of PML have been reported in patients undergoing said treatment after several prior chemotherapeutic regimens. PML's syndrome - a rare demyelinating disease of the central nervous system, resulting from reactivation of latent JC-virus, often ends in death. Patients must be closely monitored to detect the occurrence or worsening neurologic, cognitive or behavioral signs or symptoms which might be precursors of PML. In the case of suspected PML brentuximab vedotin appointment should be suspended.The recommended regimen comprises determining PML consultation neurologist, brain MRI with contrast agent gadolinium-based analysis and cerebrospinal fluid for the presence of DNA by PCR JC -virusa or brain biopsy for the presence of symptoms -virusa JC. A negative PCR result does not exclude PML. Further monitoring and evaluation is warranted if an alternative diagnosis has not been established. Brentuximab vedotin treatment should be discontinued completely in the case of confirmation of the diagnosis of PML.if an alternative diagnosis has not been established. Brentuximab vedotin treatment should be discontinued completely in the case of confirmation of the diagnosis of PML.if an alternative diagnosis has not been established. Brentuximab vedotin treatment should be discontinued completely in the case of confirmation of the diagnosis of PML.
The physician should be particularly alert to symptoms suggestive of development of PML that the patient may not notice (eg cognitive, neurological or psychiatric symptoms).
Pancreatitis
Patients undergoing treatment brentuximab vedotin, cases of acute pancreatitis have been reported, including fatal.
Patients should be closely monitored to detect for the first time appeared or increasing abdominal pain, which may be a symptom of acute pancreatitis. Examination of the patient may include physical examination, laboratory analysis for serum amylase and lipase serum and visualization of the abdominal cavity via ultrasound or other suitable diagnostic methods. In case of suspected acute pancreatitis brentuximab vedotin appointment should be suspended. Brentuximab vedotin treatment should be discontinued completely in the case of confirmation of the diagnosis of acute pancreatitis.
pulmonary toxicity
Patients undergoing treatment brentuximab vedotin, cases of pulmonary toxicity have been observed. Although not been ascertained pulmonary toxicity relationship with brentuximab vedotin risk of developing this side reaction because of the use brentuximab vedotin can not be excluded. In identifying or exacerbating pulmonary symptoms (e.g., coughing, dyspnea), necessary to the proper diagnostic evaluation and treatment of patients.
Severe and opportunistic infections
Patients undergoing treatment brentuximab vedotin, heavy and opportunistic infections were reported, such as pneumonia, Staphylococcal bacteremia, herpes zoster, oral candidiasis, sepsis / septic shock (including fatal). To identify possible severe and opportunistic infections, patients should be closely monitored during treatment.
Infusion reactions
Patients undergoing treatment brentuximab vedotin, infusion reactions have been reported, including anaphylactic.
Patients should be closely monitored during and after the infusion.
With the development of anaphylactic reactions brentuximab vedotin administration should be stopped immediately, and further treatment with this drug is discontinued. Appropriate therapeutic measures for the relief of the reaction should be taken.
With the development of infusion reactions administration of the drug should be discontinued immediately, and should be taken the necessary therapeutic measures for the relief of reactions. After resolving the symptoms infusion can be continued at a slower rate. Patients who have previously observed, infusion reactions, it is recommended to take precautionary measures prior to administration of the drug. Premedication may include paracetamol, antihistamine or a corticosteroid.
Infusion reactions occur more frequently and are most pronounced in patients with antibodies to brentuximab vedotin.
Tumor lysis syndrome
in patients undergoing treatment brentuximab vedotin was recorded tumor lysis syndrome. Patients with rapidly proliferating tumor and high tumor burden are at increased risk of tumor lysis syndrome. These patients should be closely monitored, they must be treated in accordance with the best practices of medical practice. Treatment of tumor lysis syndrome include active replenishing fluid in the body, control kidney function disorders of electrolyte balance correction, antigiperurikemicheskuyu therapy and symptomatic therapy.
peripheral neuropathy
Brentuximab vedotin treatment can cause the development of peripheral neuropathy, preferably touch. Also, cases of peripheral motor neuropathy have been reported. Peripheral neuropathy caused by introduction brentuximab vedotin usually is an effect of cumulative exposure of the medicament, and in most cases, reversible. In clinical trials, the majority of patients had relief of symptoms of peripheral neuropathy. Among patients with peripheral neuropathy has been registered, the treatment was stopped at 9%, the dose was reduced from 8% administering the next dose was delayed by 13% of patients. Patients should be monitored for the detection of neuropathy symptoms, such as hypesthesia, hyperesthesia, paresthesia, discomfort, burning sensation,neuropathic pain or weakness. In the case of developing or worsening symptoms of peripheral neuropathy may require a delay or correction of the dose until the end of treatment.
Hematological toxicity
When treating brentuximab vedotin may develop anemia, grade 3 or 4 thrombocytopenia and prolonged (? 1 week), neutropenia, grade 3 or 4. Patients undergoing treatment brentuximab vedotin was registered febrile neutropenia. Complete blood count should be performed before each administration of the drug. Patients should be monitored for signs of fever. In the case of neutropenia grade 3 or 4, it is necessary to change the dose until the end of treatment.
Stevens-Johnson syndrome and toxic epidermal necrolysis
In patients treated with brentuximab vedotin, cases of Stevens-Johnson syndrome and toxic epidermal necrolysis have been reported, including fatal. In the case of the syndrome of Stevens-Johnson and toxic epidermal necrolysis brentuximab vedotin treatm
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