Vectibix (Vectibix)

Composition Pharmacodynamics Indications Carefully Contraindications Dosing and Administration Side effects Form release / dosage
Read on
Active substancePanitumumabPanitumumab
Similar drugsTo uncover
  • Vectibix
    concentrate d / infusion 
    Amgen Europe BV     Netherlands
    • Dosage form: & nbspconcentrate for solution for infusion
    Composition:1 ml of concentrate contains:
    active substance: panitumumab - 20 mg
    Excipients: sodium acetate trihydrate - 6.8 mg, sodium chloride - 5.8 mg, acetic acid ice - to pH 5.8, water for injection - a sufficient amount.
    Description:Transparent, colorless liquid; may contain translucent or white amorphous protein particles.
    Pharmacotherapeutic group:Antitumor agent, monoclonal antibodies
    ATX: & nbsp

    L.01.X.C   Monoclonal antibodies

    L.01.X.C.08   Panitumumab

    Pharmacodynamics:

    Panitumumab is a fully human monoclonal antibody IgG2, derived from the mammalian cell line (Chinese ovaries hamster) by recombinant DNA-ttechnology.

    Panitumumab has a high affinity and specificity for the receptors of human epithelial growth factor (EGF). The EGF receptor is a transmembrane glycoprotein from the Type I receptor tyrosine kinase family, which also includes HERl / c-ErbB-1, HER2, HER3 and HER4. The EGF receptor stimulates the growth of normal epithelial cells, including skin cells and hair follicles, and is expressed on various types of tumor cells.

    Panitumumab binds to the ligand-binding domain of the EGF receptor and inhibits the autophosphorylation process, which is induced by all known EGF receptor ligands. The binding of panitumumab to the EGF receptor leads to internalization of the receptor, inhibition of cell growth processes, induction of apoptosis, and a decrease in interleukin-8 production and a vascular endothelial growth factor.
    Genes KRAS (homologue of the viral oncogene of rat karsten sarcoma 2) and NRAS (homologue of the neuroblastoma of the viral oncogene RAS) belong to the family of oncogenes RAS. Genes KRAS and NRAS encode a small guanosine triphosphate-binding protein that is involved in transduction of the signal. KRAS and NRAS is activated by various signals, including the EGF receptor, and in turn stimulates the synthesis of other intracellular proteins involved in cellular proliferation, survival and angiogenesis.
    Activating gene mutations RAS often occur in various human tumor cells and play a role, both in the process of oncogenesis, and in the progression of the tumor.
    Immunogenicity
    Like all therapeutic proteins, panitumumab has potential immunogenicity. The production of neutralizing antibodies to panitumumab was assessed using two different immunoassay screening systems to determine bound antibodies to pantimumab (ELISA, which allows the detection of high affinity antibodies, and a Biosensor that allows the determination of high and low affinity antibodies).
    Patients, whose serum was positive for the presence of antibodies in any screening immunoassay, also carried out a biological test in vitro for detection of neutralizing antibodies.
    As a monotepapia:
    - The detection of bound antibodies (except for cases of detection of antibodies prior to drug administration and temporarily positive) was <1%, as determined by the ELISA assay and 3.8%, as determined by the Biocor immunoassay.
    - Detectability of neutralizing antibodies (except for cases of detection of antibodies prior to drug administration and temporarily positive) was <1%.
    - When compared with patients in whom antibodies were not produced, the relationship between the presence of neutralizing antibodies to panitumumab and changes in pharmacokinetic parameters, efficacy and safety of the drug is not noted.
    In combination with regimens of chemotherapy on the basis of irinotecan or oxalilatine:
    - Identification of bound antibodies (except for cases of detection of antibodies prior to drug administration and temporarily positive) was 1.0%. as determined by the ELISA analysis and <1%. as was established by means of immunological analysis of Biocor.
    - Detectability of neutralizing antibodies (except for cases of detection of antibodies prior to drug administration and temporarily positive) was <1%.
    - There was no evidence of a change in the safety profile with a positive test result for antibodies to Vectibix.
    The determination of antibodies depends on the sensitivity and specificity of the method used. A variety of factors can influence the positive result of antibody determination, including the method of analysis, sampling technique, sampling time, taking concomitant medications and the nature of the underlying disease, so comparing the incidence of antibodies to panitumumab with this indicator for other drugs may be unreliable.
    Clinical efficacy
    In a clinical study, the use of Vectiblex in patients with metastatic colorectal cancer (mCRP) with wild-type genes KRAS, in whom there was a progression of the disease on the background or after previous courses of chemotherapy on the basis of fluoropyrimidine, oxalinaline or irinotecan leads to a significant increase in survival without progression (PFS). In patients with a mutant type of gene KRAS there was no positive effect on PFS.
    The efficacy of Vectibix was also evaluated in a clinical trial in patients mCRC with wild-type gene KRAS (exon 2) resistant to chemotherapy, which were randomized in a 1: 1 ratio to receive Vectibix and cetuximab. The primary endpoint was overall survival (OS). Secondary key points included survival without progression (PFS) and the frequency of an objective response (POC).
    The primary endpoint showed an overall survival benefit (95% CI: 9.4, 11.6, p = 0.001) in favor of Vectibix. There was no positive effect on PFS and there was a slight advantage in the POC in the panitumumab group compared to the cetuximab group.
    Clinical efficacy in combination with chemotherapy
    In a clinical trial, the use of Vectibix in combination with a regimen of chemotherapy on the basis of oxaliplatin, fluorouracil (FU) and calcium folinate (FOLFOX), in patients with wild-type mCRC KRAS, leads to a significant increase in survival without progression (PFS) compared with monotherapy FOLFOX. Other key endpoints included: overall survival (OB), frequency of objective response (POC), time to progression (VDR), and response time.
    In a clinical trial, the use of Vectibix in combination with rhinotoxan, fluorouracil (FU) and calcium folinate (FOI.FIRI) evaluated at key end points - overall survival (OB) and survival without progression (PFS). Other key endpoints included: overall survival (OB), time to response, time to progression (VDR), and response time.
    In patients with mCRC with KRAS wild type has been demonstrated significant an increase in PFS in the group of patients who received Vectibix. The use of panitumumab in combination with oxaliplatin or irinotecan-based chemotherapy and bevacizumab is associated with an unfavorable benefit-risk relationship regardless of gene mutation status KRAS.
    There was carried out predefined retrospective analysis of 586 patients from 597 patients with wild-type mCRC KRAS (exon 2). To assess the effect of panitumumab treatment in combination with chemotherapy FOLFIRI in the second line of therapy mCRC investigated additional mutations RAS,following KRAS exon 2 (i.e., KRAS exons 3, 4, and NRAS exons 2, 3, 4) and mutations in BRAF exon 15.
    In patients with wild type mCRC RAS, panitumumab in combination with FOLFIRI showed an advantage in PFS and 013 in comparison with monotherapy FOLFIRI.
    In this analysis, mutations BRAF predetermined the negative outcome of treatment associated with a decrease in PFS and OB in patients with wild type mCRC KRAS in exon 2, regardless of the treatment group. Data also show that mutations BRAF Do not predetermine the additional benefit of the effect of panitumumab treatment.
    In patients with wild type mCRC RAS, the advantage in PFS, OB and POC in the group of patients receiving panitumumab in combination with FOLFIRI in comparison with monotherapy FOLFIRI. For patients with additional mutations RAS after KRAS Exon 2 has not been shown to benefit from the addition of panitumumab to FOLFIRI.
    Based on the analysis of overall survival (> 80% of cases of OB), the effect of panitumumab treatment in combination with FOLFOX in comparison with monotherapy FOLFOX, with an OB status KRAS (exon 2).A predefined retrospective analysis was conducted for 641 of 656 patients with wild-type mCRC KRAS (exon 2). The primary goal of this analysis was to study the effect of panitumumab treatment in combination with FOLFOX in comparison with monotherapy FOLFOX in patients with wild-type genes RAS (KRAS and KRAS exons 2, 3 and 4) or wild-type genes RAS and BRAF (KRAS andKRAS exons 2, 3 and 4 and BRAF exon 15). In this analysis, the frequency of additional mutations RAS in the wild type of gene KRAS (exon 2) was about 16%.
    In this analysis, mutations BRAF not precursorRWe selected a negative outcome of treatment panitumumab.
    A subsequent predetermined analysis determined (n = 7) additional mutations KRAS and KRAS in exon 3 (codon 59). The codon 59 analysis also showed a predicted negative outcome for panitumumab treatment.
    Pharmacokinetics:When applying Vectibix as monotherapy or in combination with chemotherapy pharmacokinetics of the drug has a nonlinear character.
    After a single injection of panitumumab as a 1-hour infusion, the area under the concentration-time curve (AUC) increased more than it is characteristic for a dose-proportional dependence, and the clearance of the drug decreased from 30.6 to 4.6 ml / day / kg with an increase in the dose from 0.75 to 9 mg / kg. However, with the introduction of panitumumab in doses exceeding 2 mg / kg, the nature of the increase AUC was close to a dose-proportional dependence.
    If the recommended dosage regimen is observed (6 mg / kg once every 2 weeks as a 1-hour infusion), the equilibrium concentration of panitumumab is reached by the third infusion at a mean maximum (± standard deviation) and minimum concentrations of 213 ± 59 and 39 ± 14 μg / ml. respectively. Average value (± standard deviation) AUC and the clearance was 1306 ± 374 μg-day / ml and 4.9 ± 1.4 ml / kg / day, respectively. Period half-life preparation amounted to Approximately 7.5 days (range: 3.6 to 10,9 days).
    According to the results of the analysis of pharmacokinetics in individualgroups patients (predominantly aged 21-88 years), the sex of the patient, the race, the function of the liver and kidney, the use of concomitant chemotherapeutic drugs and EGF, intensive staining of the membranes (1 +, 2+, 3+) in tumor cells does not have an obvious effect on the pharmacokinetics of panitumumab .
    Pharmacokinetics in selected patient groups
    Studies of the pharmacokinetics of panitumumab in patients with impaired renal or hepatic function were not performed.
    Indications:
    Vectibix is ​​indicated for the treatment of metastatic colorectal cancer in patients with genes RAS wild type:
    - in combination with chemotherapy on the basis of fluoropyrimidine and oxaliplatin;
    - in combination with chemotherapy on the basis of fluoropyrimidine and irinotecan;
    - as a monotherapy for the progression of the disease against the background of the use of standard chemotherapy.
    Contraindications:- Vectibiks are contraindicated in patients with anamnesis of life-threatening reactions hypersensitivity to any of the components of the preparation.
    - Interstitial pneumonitis or pulmonary fibrosis.
    - The use of Vectibix in combination with chemotherapy regimen based on oxaliplatin in patients with mCRC with mutant type of genes RAS or patients with an unspecified type of gene RAS.
    - Childhood (effectiveness and safety in children under 18 years of age is not installed).
    - Pregnancy.
    - The period of breastfeeding.
    Carefully:
    Pregnancy and lactation:
    The EGF receptor is involved in the control of prenatal development of the fetus and plays a role in the processes of normal organogenesis, proliferation and differentiation of the cells of the developing embryo. Thus, Vectibix may have potential harm to the fetus when administered by pregnant women. It is known that human antibodies IgG can penetrate through the placental barrier, so panitumumab can penetrate from the mother's body into the developing organism of the fetus. Therefore, women with a safe reproductive function during Vectibiks treatment and within 2 months after it should use reliable means of contraception. If the pregnancy has developed against the background of therapy, it is necessary to explain to the patient the potential risk of abortion and the potential risk to the fetus.
    It is not known whether the panitumumab in breast milk. Since human IgG antibodies penetrate into breast milk, it can be assumed that panitumumab can also penetrate into breast milk. The possibility of absorption of the drug and its potential harm to the child are not established. During the treatment with Vectibix and within 2 months after its end, breast-feeding is not recommended.
    In experiments, a reversible effect of the drug on the menstrual cycle and a decrease in the fecundity of monkey females was shown. Concerning panitumumab can influence the possibility of developing pregnancy in women.

    Dosing and Administration:The recommended dose of Vectibix is 6 mg / kg body weight 1 every 2 weeks.
    Special patient groups
    The security and effectiveness of the Vectibix is ​​not assessed in patients with impaired kidney or liver function.
    AT when the drug is administered to people elderly dose adjustment is not it takes.
    Children
    Experience in the use of Vectibix in children is absent; The drug should not be administered to patients younger than 18 years of age.
    Recommendations for dose adjustment and administration
    When a weak or moderate signs of infusion reaction (grade 1 or 2), reduce the injection rate at 50%. If there are severe symptoms of the infusion reaction (degree 3 or 4), the introduction of Vectibix should be stopped immediately.
    Dermatological reactions
    With the development of the dermatological reaction 3 and above the severity level (NCI-CTC / CTCAE) or intolerable dermatological reaction, it is recommended to enter the following change dose.

    The onset of skin symptoms: ≥ degree 31

    Introduction

    preparation

    Vectibix

    Result

    Adjustment

    doses

    First happening

    emergedthe

    Cancel 1 or 2 doses

    Reduction in the intensity of the reaction (<3 degrees)

    Resumption of infusion at a dose of 100% of the original dose

    Improvements not has come

    Termination

    Second

    happening

    emergedthe

    Cancel 1 or 2 doses

    Reduction in the intensity of the reaction (<3 degrees)

    Renewal of infusion at a dose of 80% of the original dose

    Improvements not

    has come

    Termination

    The third

    happening

    emergedthe

    Cancel 1 or 2 doses

    Reduction in the intensity of the reaction (<3 degrees)

    The resumption of infusion at a dose of 60% of the original dose

    Improvements

    not

    has come

    Termination

    Fourth

    case of occurrence

    Abandonedthe

    -

    -

    1 - Reactions of the 3rd degree or higher are considered to be severe or life threatening.
    Instructions for the preparation and administration of a solution for infusions
    Before the infusion, Vectibix is ​​diluted in a 0.9% solution of sodium chloride for injection under aseptic conditions. It is not recommended to shake vigorously or vigorously. Do not administer the drug if there is a discoloration of the contents of the vial. From the vial of the drug climbs necessary the amount of Vectibix to obtain a dose of 6 mg / kg, which is then dissolved in a total volume of 100 ml. The final concentration should not exceed 10 mg / ml. Doses higher than 1000 mg should be dissolved in 150 ml of a 0.9% solution of sodium chloride for injection. Received solution mix gently invert the vial, do not shake.
    Vectibix should be administered intravenously via an infusion pump to the peripheral probe or a permanent catheter through an integrated 0.2 or 0.22 micron filter with a low degree of protein binding. The recommended duration of the infusion is approximately 60 minutes. If the first infusion is well tolerated, subsequent infusions can be performed within 30-60 minutes. The duration of administration of the drug in doses above 1000 mg should be approximately 90 minutes.
    Before and after administration of Vectibix, the infusion system must be washed with 0.9% sodium chloride solution to avoid mixing Vectibix with other medications or solutions for intravenous administration.
    In the case of infusion reactions, a reduction in the infusion rate of Vectibix may be required (see section "Special instructions").
    It is not recommended jet or bolus Vektibiksa introduction.

    Side effects:The most frequent adverse reactions with the use of Vectibix in monotherapy and in combination with chemotherapy (n= 2588), there were dermatological reactions, observed in approximately 93% of cases.These reactions are due to the pharmacological properties of the drug Vectibix and usually have a light or moderate severity: only 25% of cases of dermatological reactions are severe (severity level 3, according to classification NCI-CTC) and <1% life-threatening (grade 4 by NCI-CTC). Clinical management of skin reactions, including recommendations for dose adjustment, is given in the section "Special instructions". The most frequent adverse reactions that occurred in> 20% of patients were gastrointestinal disorders [diarrhea (50%), nausea (41%), vomiting (27%), constipation (23%) and abdominal pain (23%) ]: general reactions [increased fatigue (37%), pyrexia (20%); metabolic and nutritional disorders [anorexia (27%)]: infections and invasions [paronychia (20%)]; and pathology of the skin and subcutaneous tissue [rash (45%), acneiform dermatitis (39%), itching (35%). erythema (30%) and dry skin (22%)].
    Below are the data on undesirable reactions observed in patients with mCRC who received panitumumab as monotherapy or in combination with chemotherapy (n=2588).
    The safety profile of Vectibix in combination with chemotherapy includes recorded unwanted reactions of Vectibix (as a monotherapy) and the toxicity of background chemotherapy.There were no new cases of toxicity, as well as aggravation of previously reported cases of toxicity, in addition to the expected additive effects. Dermatological reactions were the most frequent undesirable reactions observed in patients taking panitumumab in combination with chemotherapy. Other undesirable reactions, most often observed in patients undergoing monotherapy, included hypomagnesemia, diarrhea and stomatitis. These undesirable reactions in some cases required the cancellation of Vectibix or chemotherapy.
    Undesirable reactions are presented in accordance with the following gradation of their occurrence frequency: Often (≥1/10), often (≥1/100, <1/10), infrequently (≥1/1000, <1/100) and rarely (≥1/10000, <1/1000).
    Infections and invasions
    Often - paronychia1.
    Often - pustular rash, cellulite1, folliculitis, a local infection, urinary tract infections.
    Infrequently - eye infections, eyelid infections.
    Violations of the blood and lymphatic system
    Often - anemia.
    Often - leukopenia.
    Immune system disorders
    Often - hypersensitivity1.
    Rarely - Anaphylactic reactions1.
    Disorders from the metabolism and nutrition
    Often hypokalemia, anorexia, hypomagnesemia.
    Often - hypokalemia, dehydration, hyperglycemia, hypophosphataemia.
    Disorders from the psyche
    Often - insomnia.
    Often - anxiety.
    From the nervous system
    Often - dizziness, headache, cholinergic syndrome.
    From the side of the organ of vision
    Often - conjunctivitis.
    Often - blepharitis, increased eyelash growth, increased lacrimation, hyperemia of the eyeball, dry eyes, itchy eyes, eye irritation.
    Infrequently - Irritation of the eyelid, keratitis.
    Rarely - ulcerative keratitis1.
    Heart Disease
    Often - tachycardia.
    Infrequently - cyanosis.
    Violations from the side of the cardio-cardiovascular system
    Often - deep vein thrombosis, decrease blood pressure, increase blood pressure, "hot flashes".
    On the part of the respiratory system
    Often - shortness of breath, cough.
    Often - pulmonary embolism, nasal bleeding.
    Infrequently - bronchospasm, dryness of the nasal mucosa.
    Frequency unknown - interstitial lung disease.
    From the digestive system
    Often - diarrhea1, nausea, vomiting, pain in the stomach, stomatitis, constipation.
    Often - rectal bleeding, dryness mucous horny areas, dyspepsia, aphthous stomatitis, cheilitis, gastroesophageal reflux disease, dry lips.
    Infrequently - chapped lips.
    From the skin and subcutaneous fat cellulose
    Often - acneiform dermatitis, rash1, erythema, itchy skin. dry skin, skin cracks, acne, alopecia.
    Often - syndrome of palmar-plantar erythrodysesthesia. skin ulcers, skin peeling, hypertrichosis, onychlasia, nail diseases, hyperhidrosis, dermatitis.
    Infrequently - angioedema1, hirsutism, ingrown nail, onycholysis.
    Rarely - skin necrosis1, Stevens-Johnson syndrome1. toxic epidermal necrolysis1.
    Disturbance of musculoskeletal and connective tissue
    Often back pain.
    Often - pain in the extremities.
    General violations and local changes
    Often - increased fatigue, pyrexia, asthenia, inflammation of the mucous membrane, peripheral edema.
    Often - chest pain, pain, chills.
    Infrequently - Infusion reactions1.
    Research
    Often - weight loss.
    Often - decrease in the concentration of magnesium in the blood.
    1 - seesection "Description of individual adverse reactions", given below.
    2 - mainly the rash includes skin toxicity. peeling leather, exfoliative rash, papular rash, itching rash, erythematous rash, generalized rash, macular rash, maculopapuluse rash, skin lesions.
    Description of individual adverse reactions
    Digestive system disorders
    In most cases, diarrhea was mild or moderate in severity. Severe cases of diarrhea have been reported (grades 3 and 4 for NCI-CTC) in 2% of patients who took Vectibix as a monotherapy and in 17% of patients. who took Vectibiks in combination with chemotherapy. It was reported development of acute renal failure the background of severe diarrhea and dehydration (see section "Special instructions").
    Infusion reactions
    During the clinical trials and postmarketing period, the following adverse reactions occurred within 24 hours after the infusion: abdominal pain, anaphylactic reactions, angioedema, back pain, bronchospasm, cardiac arrest, chest pain, chills, cyanosis, dyspnea , "hot flashes" of blood, increased blood pressure, lower blood pressure, pyrexia, tachycardia, vomiting.
    Infusion reactions (developing within 24 hours from the first administration of the drug) were observed in 3% of patients who received Vectibix in clinical studies with mCRC monotherapy. The frequency of severe reactions (degrees 3 and 4) was 0.5%. In clinical studies using the irinotecan-based chemotherapy regimen, severe infusion reactions (degrees 3 and 4 by NCI-CTC), 1% of patients taking Vectibix in combination with irinotecan-based chemotherapy (n = 951) and 0.2% of patients receiving only irinotecan-based chemotherapy (n = 594). In clinical studies using the oxalplatin-based chemotherapy regimen, severe infusion reactions were reported (grades 3 and 4 for NCI-CTC), occurred in 2.4% of patients who took Vectibix in combination with oxalnoplatin-based chemotherapy (n = 585) and 2.4% of patients receiving oxalplatin-based chemotherapy alone (n = 584). Post-marketing studies reported serious infusion reactions, including rare reports of deaths. A case of lethal anginal edema was reported in a patient with recurrent metastatic squamous cell carcinoma of the head, treated with Vectibix.The fatal complication developed after the resumption of therapy afterprevious episode of development of angioedema. Both reactions were recorded more than 24 hours after the administration of the drug (see the sections "Contraindications" and "Special instructions"). The hypersensitivity reactions that developed more than 24 hours after the infusion were also reported in the postmarketing period.
    Disturbances from the skin and subcutaneous fatty tissue
    Skin rash, developed against the background of Vectibix treatment, was most often localized on the face, upper chest and back, but in some cases it spread to the limbs. As a consequence of severe dermatological reactions, the development of infectious complications, such as sepsis, in rare cases with a legal outcome, cellulite and local abscesses, requiring surgical intervention and drainage, was also noted. The median time to the development of the first manifestations of dermatological reactions was 10 days, and the median time to their resolution after the last introduction of Vectibix was 28 days.
    Paronychial inflammation was accompanied by a swelling of the lateral nail ridges of the fingers and toes.
    Dermatological reactions (including effects on the nails) observed in patients treated with Vectibix or other inhibitors of EGF are known pharmacological effects of these drugs.
    In all clinical trials, skin reactions were observed in 93% of patients who received Vectibix as a monotherapy or in combination with chemotherapy (n= 2588). Basically it was a rash and acne dermatitis almost always of an easy or moderate nature. About severe skin reactions (grade 3 by NCI-CTC) reported in 34% of patients, and life-threatening skin reactions - in <1% of patients (grade 4 by NCI-CTC), who took Vectibix in combination with chemotherapy (n = 1536).
    Details of clinical management dermatological reactions. including recommendations for changing the dose, see section "Special instructions".
    In the post-marketing period of use, rare cases of skin necrosis, Stevens-Johnson syndrome and toxic epidermal necrolysis were reported (see section "Special instructions").
    Ophthalmic toxicity
    In the post-marketing period of use, few cases of keratitis and / or ulcerative keratitis have been reported (see p.section "Special instructions").
    Children
    There is no data on the use of Vectibiks in children, so Vectibiks can not be used to treat people younger than 18 years.
    Other special populations
    In elderly patients (≥65 years) who received Vectibiks monotherapy. there was no difference in safety and efficacy. but It was an increase in the number of serious adverse reactions in elderly patients who received Vectibix therapy in combination with irinotecan or oxaliplatin-based chemotherapy regimen compared with chemotherapy alone.
    There are no data concerning the safety of Vectibix in patients with renal and hepatic insufficiency.
    Overdose:When the recommended therapeutic dose (12 mg / kg) was exceeded, skin toxicities, diarrhea, dehydration and fatigue were approximately 2-fold, which corresponded to the drug safety profile at the recommended dose. Therapy in case of an overdose is symptomatic.
    Interaction:Data from the study on the interaction of Vectibix and irinotecan in patients with mCRC showed,that the pharmacokinetic properties of irinotecan and its active metabolite, SN-38, do not change, with the simultaneous administration of drugs. The results of a cross-sectional comparative study have shown that schemes involving irinotecan (IFL or FOLFIRI), do not affect the pharmacokinetic properties of panitumumab.
    It is not recommended the combined use of Vectibix with the chemotherapy regimen, containing irinotecan, fluoropyrimidine bolus and calcium folinate (leucovorin) (IFL regimen) and chemotherapy regimens including bevacizumab. With the appointment of panitumumab in combination with IPL, there was a high incidence of severe diarrhea, and the frequency of toxicity and death was increased with the appointment of panitumumab in combination with a chemotherapy regimen that included bevacizumab.
    Vectibix should not be given in combination with chemotherapy containing oxaliplatinum, patients with mCRC with mutant genes RAS, or in case of unspecified status RAS. In a clinical trial in patients with mCRC with a mutant gene KRAS,who received panitumumab and FOLFOX, there was a significant reduction in survival without progression and a decrease in the overall survival time.
    Predefined retrospective analysis of 641 of 656 patients with wild-type mCRC KRAS (exon 2) phase 3, established additional mutations RAS (KRAS [exons 3 and 4] or NRAS [exons 2, 3, 4]) in 16% (n = 108) patients. A decrease in GDP and OS was observed in patients with mCRC with mutant type of genes RAS, receiving panitumumab in combination with FOLFOX (n = 51) compared with monotherapy FOLFOX (n = 57) (see section "Special instructions").
    Special instructions:

    General instructions

    Vectibix treatment should be performed under the supervision of a doctor who has experience in prescribing antitumor drugs.

    Determination of genetic tumor markers

    Before starting treatment with Vectibiks, wild type genes RAS (KRAS and NRAS). Determination of mutation status should be performed by experienced laboratory technicians using a validated mutation detection technique KRAS (exons 2, 3 and 4) and NRAS (exons 2, 3, and 4).

    Undesirable reactions from soft tissues and skin

    Dermatological reactions - the class effect of inhibitors of the EGF receptor, caused by pharmacological properties were observed in practically all patients (approximately 90%) who received Vectibix. In cases of severe dermatological reactions, a change in the dose of Vectibix (≥ degree 3) (see section "Method of administration and dose").

    Treatment of dermatological reactions should be based on the severity of the manifestations and may include moisturizing, sunscreen products (sunscreen filter> 15 UFA and UVF), as well as creams containing glucocorticosteroids (percentage of hydrocortisone not exceeding 1%) for use in affected areas and / or oral antibiotics. Also, patients with signs of rash / dermatological toxicity It is recommended to use sunscreen and headwear, to limit exposure to the sun, as sunlight can enhance any possible skin reactions.

    Preventative care behind the skin, including a moisturizing, sunscreen (sunscreen filter> 15 UVA and UVF). cream containing glucocorticosteroids (percent hydrocortisone not above 1%) and oral antibiotics (for example, doxycycline), used at treatment dermatological reactions. Patients should apply moisturizing, sunscreen on the face, arms, legs, neck, back and chest every morning, and at night apply cream, containing glucocorticosteroid on the face, arms, legs, neck, back and chest during the treatment.

    It was reported about development of heavy dermatological reactions (including stomatitis), infectious complications, including sepsis and necrotizing fasciitis, in rare cases leading to death and local abscesses requiring surgical intervention. Patients who, with Vectibiksome, developed severe dermatological reactions or soft tissue reactions, or worsened the course of dermatological reactions, must be observed on subject development of appoint appropriate treatment.

    Patients who received Vectibix had life-threatening and fatal infectious complications, including necrotizing fasciitis and / or sepsis.

    When used in routine clinical practice, patients who received Vectibix rarely experienced Stevens-Johnson syndrome and toxic epidermal necrolysis.

    In case of adverse reactions from soft tissues or skin, associated with severe or life-threatening inflammatory or infectious complications, it is necessary to postpone or cancel treatment with Vectibix.

    Complications from the lungs

    FROMradiation of interstitial lung diseases, with lethal outcomes and without. appeared against the background of therapy with inhibitors of the EGF receptor. including Vectibiks, therefore, with the onset or worsening of pulmonary symptoms, Vectibix treatment should be suspended and the observed symptoms are immediately and thoroughly examined. If interstitial lung diseases are detected, Vectibix should be temporarily discontinued and appropriate treatment prescribed. In patients with interstitial pneumonitis or pulmonary fibrosis in history or with signs of interstitial ineonitis or pulmonary fibrosis, it is necessary to evaluate the likely benefit of using the drug and the risk of complications from the lungs.

    Violations of the water-electrolyte balance

    Some patients showed a progressive decrease in serum magnesium concentrations, leading to severe (grade 4) hypomagnesemia. It is necessary to periodically monitor the patients' condition for the development of hypomagnesemia and concomitant hypocalcemia before starting treatment with Vectibiks, during treatment and for 8 weeks after its completion. Recommended intake of magnesium preparations, if necessary.There were also violations of the balance of other electrolytes, including hypokalemia.

    Recommended monitoring of and adequate adequate maintenance of serum concentrations and other electrolytes.

    The preparation contains 0.150 mmol of sodium (corresponding to 3.45 mg of sodium) per 1 ml of the concentrate. In this regard, patients who adhere to a diet with a reduced sodium content during treatment should control the amount of sodium in their diet.

    Infusion reactions

    In all clinical studies of monotherapy and combination therapy of mCRR, infusion reactions (occurring within 24 hours after any infusion) were observed in approximately 4% of patients who received Vectibix, of which <1% were severe (grades 3 and 4 for NCI-CTC).

    Post-marketing studies reported serious infusion reactions, including isolated post-marketing reports of fatal outcomes. Infusion should be stopped in the event of a severe or life-threatening reaction [for example, bronchospasm, angioedema, hypotension or anaphylaxis]. Depending on the severity and / or duration of the reaction, the issue of permanent withdrawal of Vectibix should be addressed.

    In patients with mild or moderate (grade 1 and 2 in NCI-CTC)Infusion reactions should reduce the rate of infusion during the entire infusion. It is recommended to maintain a reduced infusion rate during all subsequent infusions.

    It was reported about reactions hypersensitivity, occurring more than 24 hours after the infusion, including angioedema, fatal, developed more than 24 hours after the infusion. Patients should be warned about the possibility of late development of the reaction and instructed to contact their doctor if there are symptoms of a reaction hypersensitive (cm. sections"Contraindications" and "Side effect").

    Acute kidney failure

    Acute renal failure was noted in patients with severe diarrhea and dehydration.

    Ophthalmic toxicity

    With post-marketing application, very rarely reported serious cases of keratitis and ulcerative keratitis. Patients who developed ophthalmotics when taking Vectibix should be examined for confirmation of keratitis and / or ulcerative keratitis.

    Patients with functional status 2 on a scale ECOG, Vektibiksom in combination with chemotherapy

    In a clinical study, patients with functional status 2 on a scale ECOG (Eastern Cooperative Oncology Group), There was increased toxicity and a significant reduction in survival without progression (PFS) relative to patients with status ECOG = 0 or 1 when using Vectibix in combination with a chemotherapy regimen based on fluorouracil, calcium foliait and oxalilatine (FOLFOX) in comparison with monotherapy FOLFOX in the first line of therapy. Therefore, for the treatment of mCRC in patients with status ECOG 2, an assessment of the relationship between risk and benefit before the use of Vectibix in combination with chemotherapy is recommended.

    Special instructions but expiry date

    Vectibix does not contain antimicrobial preservatives or bacteriostatic agents. From a microbiological point of view, the drug must be be used immediately after breeding. If the drug was not used immediately after breeding, user bears responsibility for the time and conditions of its storage until the next administration (no more than 24 hours at a temperature of 2 ° C to 8 ° C, unless the dilution was not conducted in controlled and validated aseptic conditions). Do not freeze dilute solution.

    Effect on the ability to drive transp. cf. and fur:Special impact studies preparation on opportunity to govern vehicles and to use complex equipment was not carried out. If undesirable reactions from the visual organs develop and / or reduce the ability to concentrate and respond quickly, patients are advised to refrain from driving vehicles or working with complex equipment prior to resolving these unwanted reactions of the drug.
    Form release / dosage:

    Concentrate for the preparation of a solution for infusions of 20 mg / ml.

    Packaging:

    The bottle contains 5 ml (100 mg / 5 ml), 10 ml (200 mg / 10 ml) or 20 ml (400 mg / 20 ml) of the concentrate.

    The bottle is made of transparent glass of hydrolytic class I with an elastomeric plug, an aluminum cap and a breakable polypropylene cap. 1 bottle is placed in a contour mesh package and then in a pack of cardboard along with instructions for use. Two transparent protective labels are affixed to each pack - the first opening control, having a longitudinal color strip.

    Storage conditions:

    Store at a temperature of 2 ° C - 8 ° C.

    Do not freeze.

    Keep in original packaging to protect from light.

    Keep out of the reach of children!
    Shelf life:

    3 years.

    Do not use after the expiration date printed on the package.

    Terms of leave from pharmacies:On prescription
    Registration number:LSR-007740/09
    Date of registration:01.10.2009 / 20.08.2013
    Expiration Date:Unlimited
    The owner of the registration certificate:Amgen Europe BVAmgen Europe BV Netherlands
    Manufacturer: & nbsp
    Representation: & nbspAMDZHEN LLC AMDZHEN LLC Russia
    Information update date: & nbsp24.01.2017
    Illustrated instructions
      Instructions
      Up