Erbitux
Erbitux: instructions for use and reviews
- 1. Release form and composition
- 2. Pharmacological properties
- 3. Indications for use
- 4. Contraindications
- 5. Method of application and dosage
- 6. Side effects
- 7. Overdose
- 8. Special instructions
- 9. Application during pregnancy and lactation
- 10. Use in childhood
- 11. In case of impaired renal function
- 12. For violations of liver function
- 13. Use in the elderly
- 14. Drug interactions
- 15. Analogs
- 16. Terms and conditions of storage
- 17. Terms of dispensing from pharmacies
- 18. Reviews
- 19. Price in pharmacies
Latin name: Erbitux
ATX code: L01XC06
Active ingredient: cetuximab (cetuximab)
Producer: Merck KGaA (MERCK, KGaA) (Germany)
Description and photo update: 2018-21-11
Prices in pharmacies: from 13,900 rubles.
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Erbitux is an antineoplastic drug based on monoclonal antibodies.
Release form and composition
Erbitux is produced in the form of a solution for infusion: a clear or slightly opalescent liquid from yellowish to colorless, the inclusion of amorphous and white visible particles is allowed (2 mg / ml: 50 ml in glass vials, in a cardboard box 1 bottle; 5 mg / ml: 10/20/50/100 ml in glass bottles, in a cardboard box 1 bottle).
The composition of the solution at a dosage of 2 mg / ml:
- active substance: cetuximab - 2 mg;
- auxiliary components: sodium chloride, sodium phosphate dihydrate, sodium dihydrogen phosphate dihydrate, water for injection.
The composition of the solution at a dosage of 5 mg / ml:
- active substance: cetuximab - 5 mg;
- auxiliary components: sodium chloride, sodium hydroxide 1M, polysorbate 80, citric acid monohydrate, glycine, water for injection.
Pharmacological properties
Pharmacodynamics
The active component of Erbitux, cetuximab, is a chimeric monoclonal antibody, IgG1 immunoglobulin, directed against EGFR (epidermal growth factor receptor). Its signaling pathways are involved in angiogenesis, control of cell survival, regulation of the cell cycle, cell migration, and the process of metastasis (cell invasion).
The affinity of cetuximab for EGFR is approximately 5–10 times higher than that characteristic of endogenous ligands. Due to blocking the binding of endogenous ligands of EGFR, inhibition of receptor functions occurs. After that, cetuximab, by inducing the internalization of EGFR, can lead to a negative regulation of the receptor. It also increases the sensitivity of cytotoxic immune effector cells to EGFR-expressing tumor cells. According to both in vitro and in vivo studies, Erbitux inhibits proliferation and induces apoptosis in human tumor cells that express EGFR. In experiments in vitro, it was found that cetuximab inhibits the production of angiogenic factors in tumor cells and blocks the migration of endothelial cells. In vivo testing showed inhibition of the production of angiogenic factors by tumor cells and a decrease in the activity of metastasis and tumor angiogenesis.
Erbitux does not bind to other receptors in the HER family.
Proto-oncogene KRAS (Kirsten Rat Sarcoma viral oncogene homolog) is a homologue of the viral oncogene of rat sarcoma Kirsten, a downstream central signal transducer for EGFR. Activation of KRAS EGFR in tumors enhances the proliferation of pro-angiogenic factors production.
The oncogenic mutation KRAS, which contributes to its constitutive activity, is one of the most common cancer oncogenic mutations. As a result of its action in the active region (codons 12 and 13), the KRAS protein is present in an activated state, transmitting a signal for proliferation into the nucleus, regardless of the EGFR signal.
In the case of metastatic colorectal cancer, KRAS has a 30 to 50% chance of mutation. The formation of human anti-chimeric antibodies (AHAC) occurs as a result of exposure to a class of chimeric antibodies. At present, there is not enough information on the mechanism of AHACH production. Measured AHAC titers, in general, are detected in 3.4% of the studied patients with frequencies in the range of 0.0–9.6% in studies with similar indications. The appearance of AChAC with the development of allergic reactions or any other undesirable effects of cetuximab is not correlated.
Pharmacokinetics
With intravenous infusion of 5 to 500 mg / m 2 cetuximab once a week, Erbitux exhibits dose-dependent pharmacokinetics.
The main pharmacokinetic characteristics of cetuximab:
- absorption and distribution: at an initial dose of 400 mg / m 2 body surface area, the average value of the maximum concentration (Cmax) is 185 ± 55 μg / ml; the volume of distribution (Vd) is roughly equivalent to the vascular region supplying blood to the affected area - from 1.5 to 6.2 l / m 2, the average value is 2.9 l / m 2; the average clearance is 0.022 l / h / m 2… In monotherapy regimen: cetuximab reaches stable serum concentrations after 3 weeks of use; Cmax is 155.8 μg / ml after 3 weeks and 151.6 μg / ml after 8 weeks, the average value of the decrease in plasma concentrations is 41.3 and 55.4 μg / ml, respectively; when Erbitux is used with irinotecan, the average decrease in plasma concentrations after 12 weeks is 50.0 μg / ml, after 36 weeks - 49.4 μg / ml;
- metabolism and excretion: the metabolism of monoclonal antibodies occurs by their biodegradation to smaller molecules (small peptides or amino acids). The half-life (T 1/2) of cetuximab in the prescribed doses is long and is about 70-100 hours.
The pharmacokinetics of cetuximab are unaffected by the race, gender, age, and renal and hepatic function of the patient.
Indications for use
According to the instructions, Erbitux is recommended for the following pathologies:
- metastatic colorectal cancer: with a wild-type KRAS gene and with EGFR expression (as part of a combination treatment with standard chemotherapy);
- metastatic colorectal cancer: with the ineffectiveness of previous chemotherapy with the inclusion of irinotecan / oxaliplatin, and with intolerance to irinotecan (for monotherapy);
- locally advanced PRGSH (squamous cell carcinoma of the head and neck) (as part of a combination treatment with radiation therapy);
- PRGSH recurrent or metastatic: with the ineffectiveness of previous chemotherapy with platinum drugs (including for monotherapy).
Contraindications
Absolute:
- pregnancy and lactation (lactation period);
- children and adolescents under 18 years of age;
- severe hypersensitivity (3-4 degrees) to cetuximab.
Relative contraindications for which Erbitux should be used with caution: liver / kidney dysfunction [currently there is no data on the use of Erbitux at levels exceeding the upper limit of normal (UHN): bilirubin and serum creatinine - 1.5 times; transaminases - 5 times], inhibition of bone marrow hematopoiesis, a history of cardiopulmonary diseases, as well as old age.
Instructions for the use of Erbitux: method and dosage
Erbitux Infusion Solution is administered as a slow intravenous infusion at a rate of ≤ 10 mg / min. Before the introduction of the drug, premedication with antihistamines and prednisolone is mandatory.
Recommended dosage (for all indications): the drug is administered once a week at an initial dose (first infusion) - 400 mg / m 2, infusion time - 2 hours; subsequent infusion at a dose of 250 mg / m 2, duration 1 hour.
Combination therapy for colorectal cancer requires adherence to the recommendations for modifying the doses of the concomitant Erbitux chemotherapy drug set forth in the instructions for this drug. The chemotherapy drug should be administered no earlier than one hour after the end of the Erbitux infusion. Cetuximab is recommended until persistent symptoms of disease progression appear.
It is recommended to start treatment of PRGSH in combination with Erbitux with radiation therapy 7 days before the onset of ionizing radiation, and continue weekly infusion of cetuximab until it ends.
In relapsing or metastatic PRGSH, Erbitux is used in combination with platinum-based chemotherapy as maintenance treatment until signs of disease progression appear. Chemotherapy is given at least one hour after the end of the cetuximab infusion.
If patients develop skin reactions of grade 3 toxicity according to the NCI-CTC (National Cancer Institute) scale, therapy with Erbitux should be discontinued. Its renewal is allowed only with a decrease in toxicity to 2 degrees.
Recommendations for correcting the dosage regimen of Erbitux in the development of skin reactions:
- first-time severe skin reaction: therapy is interrupted, and after a decrease in the degree of toxicity, resumed without changing the dose;
- secondary and tertiary development of a severe skin reaction: therapy is interrupted, and after reducing the degree of toxicity to the 2nd, it is resumed with lower doses of the drug (after the second episode - from 200 mg / m2 of body surface, after the third - from 150 mg / m2 2);
- severe skin reaction developing for the fourth time or inability to reduce the skin reaction to the 2nd degree of severity after drug withdrawal: cetuximab therapy should be discontinued.
Erbitux application rules:
- Administer intravenously only using an infusion pump, gravity drip system, or syringe pump.
- Use a separate infusion set that must be flushed with sterile 0.9% sodium chloride solution at the end of the infusion.
- Do not mix the solution with other medicinal substances / products.
- Use ethyl vinyl acetate, polyethylene, polyvinyl chloride infusion bags, as well as ethyl vinyl acetate, polyethylene, polyvinyl chloride, polybutadiene, or polyurethane infusion systems and polypropylene syringes for the syringe pump.
Before the introduction of the solution in a system with an infusion pump or a gravity drip, it is necessary to draw it in the required amount into a sterile syringe with a volume of at least 50 ml and transfer it from the vial to a sterile container / bag for infusion solutions, and then set the recommended injection rate.
Before the introduction of the solution in a system with a syringe pump, it is necessary to draw it in the required amount into a sterile syringe, which is then installed into the syringe pump, then the infusion system is connected to the syringe, the recommended infusion rate is set and the infusion begins. The procedure is repeated until the calculated dose is fully infused.
The Erbitux solution does not contain antibacterial preservatives and bacteriostatic components, therefore, it should be handled strictly following the rules of asepsis. It is recommended to use the drug as soon as possible after opening the bottle.
If it is impossible to use the solution immediately, it can be stored for no more than 24 hours at a temperature of 2–8 ° C.
Side effects
The main adverse reactions when using cetuximab: skin manifestations - up to 80%, hypomagnesemia - 10%, infusion reactions with moderate symptoms - more than 10%, infusion reactions with severe symptoms - 1%.
The frequency of systemic organ side effects (very often - no more than 0.1%; often - from 0.1 to 0.01%; sometimes - from 0.01 to 0.001%; rarely - from 0.001 to 0.0001%; extremely rarely - less than 0.0001%):
- nervous system: often - headache;
- respiratory system: sometimes - pulmonary embolism;
- digestive system: often - nausea / vomiting, diarrhea; very often - an increase in the activity of hepatic transaminases [aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP)];
- organ of vision: often - conjunctivitis; sometimes - keratitis, blepharitis;
- dermatological reactions: very often - peeling / dry skin, hypertrichosis, acne-like rash and (or) itching, changes in the nail plates (paronychia). Skin reactions mainly develop at the beginning of treatment (the first 3 weeks) and after discontinuation of Erbitux usually go away without consequences (provided that the dosage regimen is adjusted). In case of violation of the integrity of the skin, the development of superinfections is very rarely possible, aggravated by inflammation of the subcutaneous fat, erysipelas, and in some cases, potentially dangerous staphylococcal epidermal necrolysis (Lyell's syndrome) or sepsis. About 15% of dermatological reactions are pronounced; in isolated episodes, skin necrosis may develop;
- metabolism: very often - hypomagnesemia; often - hypocalcemia, anorexia (accompanied by weight loss);
- blood coagulation system: sometimes - deep vein thrombosis;
- infusion reactions: very often - mild / moderate reactions (chills, fever, nausea / vomiting, dizziness, headache, shortness of breath); often - severe reactions that usually develop within an hour during the first infusion or several hours after the first / subsequent infusions (airway obstruction / bronchospasm, decrease or increase in blood pressure, loss of consciousness, shock); extremely rare - angina pectoris, myocardial infarction, cardiac arrest. The main mechanism for the development of such reactions has not been established, probably some of them are of an anaphylactoid / anaphylactic nature;
- others: mucositis, due to which the development of nosebleeds is possible.
Overdose
There are no data on cases of overdose of cetuximab. To date, there is no experience of using Erbitux in single doses exceeding 400 mg / m 2, or subsequent weekly use at a dose of more than 250 mg / m 2.
special instructions
Treatment with Erbitux is required under the supervision of a specialist with experience in the use of anticancer drugs.
Before the start of the course and periodically during therapy, it is necessary to monitor the concentration of electrolytes in blood serum and correct violations of the water-salt balance due to the risk of developing reversible hypokalemia (due to diarrhea), hypocalcemia, hypomagnesemia.
Infusion reactions during the administration of Erbitux usually develop against the background of the first infusion or within an hour after the end of the administration of the solution. But they can also appear after a few hours or with repeated injections. The patient should be warned about the possibility of such delayed reactions and instructed to immediately consult a doctor immediately after their occurrence.
If a mild or moderate reaction associated with infusion is detected, the rate of administration of the solution should be reduced. Subsequent infusions should also be performed at a reduced rate. In the case of the development of severe symptoms of an infusion reaction, it is required to immediately interrupt the administration of the solution with the termination of therapy with Erbitux in the future, and take into account the possible need for emergency medical care.
Patients with a history of heart and lung disease should be given special attention. There is evidence of individual cases of interstitial pulmonary disorders, the causal relationship of which with the use of Erbitux has not been identified. With the development of interstitial lung lesions against the background of the administration of Erbitux, the infusion is stopped immediately and appropriate treatment is prescribed.
If skin reactions of 3-4 degrees of toxicity on the NCI-CTC scale appear, the dose and regimen of Erbitux administration are adjusted in accordance with the recommendations set out above.
If Erbitux is used in combination with chemicals, you should carefully study the instructions for their medical use.
Until now, there is experience with the use of cetuximab only in patients with normal renal / liver function: with serum creatinine and bilirubin levels not exceeding the upper limit of normal (ULN) by more than 1.5 times and the level of transaminases not more than 5 times.
There are also no data on the use of cetuximab in patients with inhibition of bone marrow hematopoiesis (hemoglobin level <9 g / dL, leukocyte concentration <3000 / μl, absolute neutrophil count <1500 / μl and platelet count <100,000 / μl).
Influence on the ability to drive vehicles and complex mechanisms
If the patient notes symptoms that affect the ability to concentrate and the speed of reaction associated with treatment, he is not recommended to drive vehicles and perform potentially hazardous activities during the course of therapy.
Application during pregnancy and lactation
Erbitux is not indicated for pregnancy and breastfeeding. It is also required to refrain from breastfeeding for 2 months after the last dose of cetuximab.
Pediatric use
The efficacy and safety of Erbitux in pediatric practice have not been established, therefore the drug is not prescribed for children and adolescents under 18 years of age.
With impaired renal function
Erbitux is used with caution in case of impaired renal function.
For violations of liver function
Erbitux is used with caution in case of liver dysfunction.
Use in the elderly
Erbitux is used with caution to treat elderly patients.
Drug interactions
Erbitux, used in combination with fluorouracil by infusion, in comparison with the use of fluorouracil alone, can increase the risk of coronary ischemia and thrombosis (before myocardial infarction), as well as palmar-plantar erythrodysesthesia.
With the combined use of cetuximab and irinotecan, no changes in the pharmacokinetics of both drugs were observed.
Other studies on drug interactions of Erbitux in humans have not been conducted.
Due to the lack of data from studies of the compatibility of cetuximab with other medicinal substances / preparations, it is prohibited to mix them.
Analogs
Erbitux analogs are Bevacizumab, Avastin, Acellbia, Gertikad, Herceptin, Reditux, Kadsila and others.
Terms and conditions of storage
Keep out of the reach of children. Store at 2–8 ° С. Do not freeze.
The shelf life is 3 years.
Terms of dispensing from pharmacies
Dispensed by prescription.
Erbitux reviews
Most reviews of Erbitux, like other anticancer drugs, indicate its increased ability to provoke adverse reactions.
Due to the severity of the underlying disease, an assessment of the effectiveness of such drugs can only be given by a qualified specialist with versatile experience in the treatment of oncological lesions, who is able to compare and analyze the long-term results of using different drugs.
Price for Erbitux in pharmacies
Depending on the region and the pharmacy network, the price of Erbitux, solution for infusion, in a dosage of 5 mg / ml, for 1 bottle (bottle) of 20 ml varies from 13,000 to 21,000 rubles.
Erbitux: prices in online pharmacies
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Drug name Price Pharmacy |
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Erbitux 5 mg / ml solution for infusion 20 ml 1 pc. RUB 13,900 Buy |
Maria Kulkes Medical journalist About the author
Education: First Moscow State Medical University named after I. M. Sechenov, specialty "General Medicine".
Information about the drug is generalized, provided for informational purposes only and does not replace the official instructions. Self-medication is hazardous to health!
