Herceptin
Herceptin: 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. Drug interactions
- 11. Analogs
- 12. Terms and conditions of storage
- 13. Terms of dispensing from pharmacies
- 14. Reviews
- 15. Price in pharmacies
Latin name: Herceptin
ATX code: L01XC03
Active ingredient: trastuzumab (trastuzumab)
Manufacturer: F. Hoffmann-La Roche Ltd. (Switzerland)
Description and photo update: 2019-14-08
Prices in pharmacies: from 9998 rubles.
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Herceptin is an anticancer drug based on monoclonal antibodies.
Release form and composition
Dosage forms of Herceptin:
- Lyophilisate for preparation of solution for infusion: powder from light yellow to white; reconstituted solution - colorless or light yellow, transparent or slightly opalescent (in colorless glass vials, 1 vial in a cardboard box);
- Lyophilisate for the preparation of a concentrate for the preparation of a solution for infusion: a powdery mass from light yellow to white; reconstituted solution - transparent or slightly opalescent from colorless to light yellow (in colorless glass bottles, in a cardboard box 1 bottle complete with a solvent);
- Solution for subcutaneous (s / c) administration: clear or opalescent liquid, colorless or yellowish (5 ml each in colorless glass bottles, 1 bottle in a cardboard box).
The active ingredient of Herceptin is trastuzumab:
- 1 bottle with lyophilisate for preparation of solution for infusion - 150 mg;
- 1 bottle with a lyophilisate for the preparation of a concentrate for the preparation of a solution for infusion - 440 mg;
- 1 bottle with a solution for subcutaneous administration - 600 mg.
Auxiliary components:
- Lyophilisate for preparation of solution for infusion: α, α-trehalose dihydrate, L-histidine hydrochloride, polysorbate 20, L-histidine;
- Lyophilizate for the preparation of a concentrate for the preparation of a solution for infusion: L-histidine, α, α-trehalose dihydrate, L-histidine hydrochloride, polysorbate 20;
- Solution for s.c. administration: polysorbate 20, recombinant human hyaluronidase (rHuPH20), L-histidine hydrochloride monohydrate, L-methionine, α, α-trehalose dihydrate, L-histidine, water for injection.
Solvent: benzyl alcohol, water for injection.
Pharmacological properties
Pharmacodynamics
Trastuzumab consists of recombinant DNA-derived humanized monoclonal antibodies that selectively interact with the extracellular domain of human epidermal growth factor 2 (HER2) receptors. These antibodies are IgG 1, which are composed of human regions (constant heavy chain segments) and murine regions of the p185 HER2 antibody that determine complementarity to HER2.
The proto-oncogene HER2 or c-erB2 encodes a transmembrane receptor-like protein with a molecular weight of 185 kDa. Its structure is similar to that of other members of the epidermal growth factor receptor family. Overexpression of HER2 is detected in the tissue affected by primary breast cancer (BC) in 15–20% of patients.
The overall frequency of detection of HER2-positive status in the tissues of extensive gastric cancer during screening of patients is 15% IHC3 + (IHC - immunohistochemical study) and IHC2 + / FISH + (in situ hybridization method), or 22.1% - when using the more extensive definition of FISH + or IHC3 +. Amplification of the HER2 gene causes overexpression of the HER2 protein localized on the membrane of tumor cells, which, in turn, provokes permanent activation of the HER2 receptor. The extracellular domain of the receptor (ECD, p105) can penetrate (“slough off”) into the bloodstream and be detected in serum samples. Research results prove that patients with breast cancer who overexpress or amplify HER2 in tumor tissues have a lower survival rate without symptoms of the disease compared to patients,which lack overexpression or amplification of HER2 in tumor tissue.
Trastuzumab blocks the proliferation of HER2 overexpressing human tumor cells in vitro and in vivo. In vitro, the antibody-dependent cellular cytotoxicity of this substance is mainly directed to tumor cells that overexpress HER2.
During the course of neoadjuvant-adjuvant therapy, antibodies to trastuzumab are determined in 7% of patients who received intravenous Herceptin (this does not depend on the initial level of antibodies).
The clinical significance of these antibodies has not been studied. However, they do not appear to adversely affect safety, efficacy (as determined by the complete pathological response), or the pharmacokinetics of the drug when administered intravenously.
There is no evidence of immunogenicity when using Herceptin in the treatment of stomach cancer.
Pharmacokinetics
The pharmacokinetics of trastuzumab has been studied in patients with metastatic breast cancer (mBC) and early stages of breast cancer, as well as in patients with a diagnosis of advanced gastric cancer. The study of drug-drug interactions has not been specifically conducted.
Mammary cancer
With the introduction of Herceptin in the form of infusions of short duration at a dose of 500, 250, 100, 50 and 10 mg once a week, its pharmacokinetics remained non-linear. As the dose was increased, the clearance of trastuzumab decreased.
The half-life of the active substance varies from 28 to 38 days, so the period of excretion of trastuzumab after drug withdrawal reaches 27 weeks (190 days or 5 half-lives).
The equilibrium state is reached after approximately 27 weeks. When using the population pharmacokinetic method (model-dependent analysis, two-chamber model) for evaluating the results of studies of phases I, II and III in mBC, the median of the estimated area under the concentration-time curve (AUC) in equilibrium after 3 weeks was equal to 1677 mg · day / l after the introduction of 3 doses (2 mg / kg) every week and 1793 mg · day / l with the introduction of Herceptin 3 weeks later at a dose of 6 mg / kg. The calculated medians of the maximum concentration were 104 and 189 mg / L, and the minimum concentration was 64.9 and 47.3 mg / L. The average equilibrium minimum concentration on day 21 of cycle 18 (the last cycle with a duration of therapy for 1 year) was 68.9 μg / ml, and the average equilibrium maximum concentration was 225 μg / ml in patients with early stages of breast cancer.who received trastuzumab at a loading dose of 8 mg / kg, then switched to a maintenance dose of 6 mg / kg (the decrease occurred after 3 weeks). These indicators were comparable to those in patients with mBC.
For a patient weighing 68 kg, the standard clearance of trastuzumab is 0.241 L / day.
In all clinical studies, the volume of distribution in the central chamber is 3.02 liters, and in the peripheral chamber - 2.68 liters for an ordinary patient.
In the blood serum of some patients with breast cancer and HER2 overexpression, a circulating extracellular domain of the HER2 receptor (antigen “exfoliating” from the cell surface) was found. In 64% of patients undergoing examination, in the initial serum samples, the antigen “exfoliating” from the cell was determined at a concentration equal to 1880 ng / ml (the median is 11 ng / ml). In patients with a high content of antigen "exfoliating" from the cell, with the introduction of Herceptin every week, the therapeutic concentration of trastuzumab in serum was determined by the 6th week. There is no significant relationship between the initial concentration of the antigen “exfoliating” from the cell and the clinical response.
Advanced stomach cancer
To study the pharmacokinetics of trastuzumab against the background of an equilibrium state in patients with advanced gastric cancer after administration of Herceptin at a loading dose of 8 mg / kg, followed by administration of the drug at a dose of 6 mg / kg every 3 weeks, a pharmacokinetic nonlinear two-chamber population method was used using the results of a phase III study …
The reported range of serum trastuzumab concentrations was lower, indicating a higher total clearance of Herceptin in patients with advanced gastric cancer than in patients with breast cancer who received the same doses of the drug. The reason for this remains unknown.
At high concentrations, total clearance tends to be linear with dose. The half-life is approximately 26 days.
The median of the estimated AUC parameter (in an equilibrium state over a three-week period) is 1213 mg day / L, the median of the maximum concentration in the equilibrium state is 132 mg / L, and the median of the minimum concentration in the equilibrium state is 27.6 mg / L.
There is no information on the content of the circulating extracellular domain of the HER2 receptor (antigen “exfoliating” from the cell) in the serum of patients with gastric cancer.
Separate studies of the pharmacokinetics of trastuzumab in patients with renal / liver dysfunction or in elderly patients have not been conducted. The patient's age does not affect the pharmacokinetic parameters of trastuzumab.
Indications for use
According to the instructions, Herceptin is used to treat metastatic breast cancer with tumor overexpression of HER2:
- Monotherapy (after one or more chemotherapy regimens);
- Combination treatment with docetaxel or paclitaxel (in the absence of previous first-line chemotherapy);
- Combined treatment with aromatase inhibitors of postmenopausal women with positive hormone receptors (estrogen and / or progesterone).
All forms of Herceptin are prescribed for early stage breast cancer with overexpression of HER2:
- Adjuvant therapy after surgery, completion of neoadjuvant or adjuvant chemotherapy, radiation therapy;
- Combination with docetaxel or paclitaxel after adjuvant chemotherapy with cyclophosphamide and doxorubicin;
- Combination with docetaxel and carboplatin for adjuvant chemotherapy;
- Combination with neoadjuvant chemotherapy and subsequent adjuvant monotherapy with Herceptin when the tumor is more than 2 cm in diameter or locally advanced disease, including an inflammatory form.
In addition, the use of two forms of lyophilisate is indicated in the treatment of advanced adenocarcinoma of the gastroesophageal junction or stomach with overexpression of HER2. The drug is prescribed simultaneously with capecitabine or intravenous (IV) fluorouracil and platinum drug (in the absence of previous anticancer therapy for metastatic disease).
Contraindications
- Severe dyspnea at rest, requiring maintenance oxygen therapy or caused by lung metastases;
- Age under 18;
- The period of pregnancy and breastfeeding;
- Hypersensitivity to drug components.
With caution, Herceptin should be prescribed for ischemic heart disease, arterial hypertension, heart failure, concomitant lung diseases or metastases in the lungs, prior therapy with cardiotoxic drugs (anthracyclines, cyclophosphamide).
In addition, the solution for subcutaneous administration is contraindicated in the early stages of breast cancer in patients with angina pectoris, a history of myocardial infarction, chronic heart failure (NYHA functional class II-IV), cardiomyopathy, left ventricular ejection fraction (LVEF) less than 55%, clinically significant heart defects, arrhythmias, uncontrolled arterial hypertension, hemodynamically significant pericardial effusion, with simultaneous use as part of adjuvant therapy with anthracyclines.
With caution, a solution is prescribed for subcutaneous administration in patients with LVEF less than 50%, in elderly patients.
Instructions for the use of Herceptin: method and dosage
Both forms of lyophilisate are administered only by intravenous drip.
Herceptin in the form of a solution is administered sc.
The use of the drug is indicated only in a hospital setting under the supervision of a physician with experience in the use of cytotoxic chemotherapy.
Testing for HER2 tumor expression should be performed prior to use.
Side effects
- Neoplasms of a benign, malignant, unspecified nature (including polyps and cysts): unknown - the progression of the neoplasm, the progression of a malignant neoplasm;
- Infections and parasitic pathologies: often - cystitis, neutropenic sepsis, Herpes zoster, sinusitis, influenza, skin infections, upper respiratory tract infections, rhinitis, urinary tract infections, phlegmon, erysipelas; infrequently - sepsis;
- Lymphatic system and hematopoietic system: very often - febrile neutropenia; unknown - hypoprothrombinemia;
- Cardiovascular system: very often - a violation of the heart rhythm, an increase and decrease in blood pressure (BP), palpitations, flutter of the ventricles or atria, hot flashes, a decrease in the left ventricular ejection fraction; often - congestive heart failure, cardiomyopathy, supraventricular tachyarrhythmia, vasodilation, arterial hypotension; infrequently - pericardial effusion; unknown - pericarditis, cardiogenic shock, gallop rhythm, bradycardia;
- Immune system: often - hypersensitivity reactions; unknown - anaphylactic reactions and / or shock;
- Mental disorders: often - depression, anxiety, impaired thinking;
- Metabolism: often - anorexia, weight loss; unknown - hyperkalemia;
- Nervous system: very often - dizziness, tremors, headaches; often - muscle hypertonicity, peripheral neuropathy, ataxia, drowsiness; rarely - paresis; unknown - cerebral edema;
- Sense organs: very often - increased lacrimation, conjunctivitis; often dry eyes; infrequently - deafness; unknown - retinal hemorrhage, edema of the optic nerve head;
- Respiratory system, mediastinal and chest organs: very often - cough, wheezing, epistaxis, rhinorrhea, shortness of breath; often - functional disorders of the lungs, bronchial asthma; rarely - pneumonitis; unknown - respiratory failure, pulmonary fibrosis, acute pulmonary edema, pulmonary infiltration, acute respiratory distress syndrome, hypoxia, bronchospasm, decreased hemoglobin oxygen saturation, pulmonary edema, orthopnea, laryngeal edema;
- Digestive system: very often - diarrhea, nausea, vomiting, abdominal pain, swelling of the lips; often - dry mouth, pancreatitis, hepatitis, pain in the liver, hepatocellular disorder, hemorrhoids; rarely, jaundice; unknown - liver failure;
- Dermatological reactions: very often - rash, facial edema, erythema; often - itching, dry skin, hyperhidrosis, acne, ecchymosis, maculopapular rash; unknown - angioedema;
- Musculoskeletal system and connective tissues: very often - myalgia, muscle stiffness, arthralgia; often - muscle spasms, back pain, arthritis, neck pain, ossalgia;
- Kidneys and urinary tract: often - kidney disease; unknown - glomerulonephropathy, membranous glomerulonephritis, renal failure;
- Genitals and mammary glands: often - breast inflammation or mastitis;
- Influence on pregnancy, postpartum and perinatal conditions: unknown - fatal renal hypoplasia and lung hypoplasia in the fetus, oligohydramnios;
- Others: very often - chest pains, chills, weakness, asthenia, flu-like syndrome, pain, fever, reactions associated with drug administration; often - swelling, malaise, bruise.
The most common and dangerous adverse reactions to Herceptin use:
- Reactions caused by the administration of the drug or hypersensitivity reactions: respiratory distress syndrome, nausea, shortness of breath, chills and / or fever, rash, tachycardia, arterial hypotension, bronchospasm, wheezing in the lungs, decreased oxygen saturation of hemoglobin, vomiting, headache; local reactions - redness, swelling, itching, rash at the injection site;
- Cardiotoxicity: often - heart failure (NYHA functional class II-IV), associated with a fatal outcome. When trastuzumab is used in combination with adjuvant chemotherapy, the incidence of symptomatic congestive heart failure does not differ from that when receiving chemotherapy alone and is slightly higher when taxanes and Herceptin are used sequentially. The safety of resuming or continuing therapy in case of cardiotoxicity has not been studied; to improve the condition of patients, it is recommended to prescribe standard therapy, including cardiac glycosides, diuretics, beta-blockers and / or angiotensin-converting enzyme inhibitors. In most cases, with clinical signs of benefit from Herceptin, therapy is continued without the appearance of clinically significant additional cardiac events;
- Lung disorders: infiltrates in the lungs, pneumonia, acute respiratory distress syndrome, pneumonitis, pleural effusion, respiratory failure, acute pulmonary edema and other severe complications from the lungs, including fatal ones;
- Hematological toxicity: very often - febrile neutropenia; often - anemia, leukopenia, thrombocytopenia, neutropenia; unknown - hypoprothrombinemia. The risk of neutropenia is slightly higher when combined with docetaxel after anthracycline therapy.
In addition, Herceptin causes side effects that are typical for each of the dosage forms of the drug.
Lyophilisate for preparation of solution for infusion and lyophilisate for preparation of concentrate for preparation of solution for infusion
- Infectious and parasitic pathologies: often - infections, pneumonia, nasopharyngitis;
- Lymphatic system and hematopoietic system: often - neutropenia, leukopenia, anemia, thrombocytopenia;
- Mental disorders: often - insomnia;
- Nervous system: often - paresthesia, dysgeusia;
- Respiratory system, mediastinal and chest organs: often - pharyngitis; infrequently - pleural effusion;
- Digestive system: often - constipation, pancreatitis, dyspepsia;
- Dermatological reactions: often - alopecia, violation of the structure of the nails; unknown - urticaria, dermatitis;
- Others: often - mucositis, peripheral edema.
Solution for subcutaneous administration
- Infectious and parasitic pathologies: very often - infections, nasopharyngitis; often - pharyngitis;
- Lymphatic system and hematopoietic system: very often - thrombocytopenia, neutropenia, leukopenia, anemia; unknown - immune thrombocytopenia;
- Mental disorders: very often - insomnia;
- Nervous system: very often - dysgeusia, paresthesia;
- Respiratory system: very often - pneumonia; often pleural effusion; unknown - interstitial lung disease;
- Digestive system: very often - stomatitis, dyspepsia, constipation;
- Dermatological reactions: very often - violation of the structure of the nails, alopecia, palmar-plantar syndrome; often - onychoclasia, dermatitis; infrequently - urticaria;
- Musculoskeletal system: often - pain in the limbs;
- Others: very often - mucositis, peripheral edema.
In addition, frequent and dangerous adverse reactions during the use of a solution for subcutaneous administration:
- Infections: infection of postoperative wounds, acute pyelonephritis, respiratory tract infections, sepsis;
- Increased blood pressure: more often in patients with a history of hypertension.
Overdose
In the course of clinical studies, cases of Herceptin overdose have not been reported. The condition of patients after a single injection of the drug in doses of more than 10 mg / kg has not been studied. When the drug was administered at doses ≤ 10 mg / kg, it was well tolerated.
special instructions
Herceptin is administered under aseptic conditions.
Before the introduction, it is imperative to check the labeling and make sure that the dosage form corresponds to the purpose - for intravenous drip or subcutaneous administration.
You can not enter Herceptin in the form of a lyophilisate in / in bolus or jet, solution for subcutaneous administration - in / in.
Solution for subcutaneous administration is a ready-to-use preparation, it cannot be mixed with other medicinal products. Before use, you must make sure that there are no mechanical impurities and color changes in the solution.
The trade name and batch number of the drug should be indicated in the patient's medical card. Only the attending physician can replace Herceptin with another biological agent.
HER2 testing is performed only in a specialized laboratory capable of ensuring the quality of the testing procedure.
Herceptin is indicated in metastatic or early stage breast cancer with only tumor overexpression of HER2, lyophilisate is also used in metastatic gastric cancer with tumor overexpression of HER2, established using accurate and validated detection methods.
Before starting the use of Herceptin, it is necessary to compare the potential benefits and risks of treatment.
When prescribing the drug, especially in the case of previous therapy with anthracycline drugs and cyclophosphamide, patients need a thorough cardiological examination with anamnesis, physical examination, electrocardiogram, echocardiography and / or radioisotope ventriculography or magnetic resonance imaging.
Treatment should be accompanied by regular (once every 3 months) monitoring of the heart function, and in case of asymptomatic heart dysfunction, every 1.5-2 months. Cardiological examination is carried out once every 6 months within 24 months after the end of the administration of Herceptin.
In metastatic breast cancer, it is not recommended to prescribe Herceptin in combination with anthracyclines.
Infusion reactions can occur both with the introduction of Herceptin, and several hours after the infusion. When they appear, it is necessary to stop the administration and carefully monitor the patient until the symptoms are completely eliminated.
Severe complications associated with pulmonary disorders can be fatal, therefore, patients with risk factors should be under constant medical supervision. With caution, Herceptin is administered with previous or concomitant therapy with other antineoplastic agents (radiation therapy, gemcitabine, taxanes, vinorelbine).
Neoadjuvant-adjuvant therapy is not recommended for patients over 65 due to limited clinical experience.
To reduce the risk of developing adverse reactions to the introduction of Herceptin, premedication can be used. The use of analgesics, antipyretics, including paracetamol, or antihistamines (diphenhydramine) is indicated. Reactions with intravenous administration are successfully suppressed by the use of oxygen inhalation, beta-adrenostimulants, glucocorticosteroids.
If undesirable reactions occur during drug administration, the patient should not drive vehicles and mechanisms.
Application during pregnancy and lactation
During treatment with Herceptin and for at least 7 months after the end of therapy, women of reproductive age should use reliable methods of contraception.
If pregnancy has occurred, it is necessary to warn the woman about the risk of negative effects on the fetus. When continuing treatment with the drug, the pregnant patient should be under constant supervision of doctors of various specialties.
There is no reliable information about the possible effect of Herceptin on reproductive capacity in women. The results of experiments on animals indicate the absence of impaired fertility or negative effects on the fetus.
During therapy and for at least 7 months after its end, breastfeeding is not recommended.
Drug interactions
Herceptin in the form of a lyophilisate is incompatible with 5% dextrose solution, it cannot be dissolved or mixed with other agents.
Clinical studies have not noted interactions while using trastuzumab with other drugs.
Analogs
An analogue of Herceptin is Trastuzumab.
Terms and conditions of storage
Keep out of the reach of children.
Store at 2-8 ° C.
Shelf life: lyophilisate - 48 months, solution - 21 months.
Terms of dispensing from pharmacies
Dispensed by prescription.
Reviews about Herceptin
Basically, reviews about Herceptin are left by patients who have undergone treatment with it. They are predominantly positive, since this drug is well tolerated by patients. It is usually reported that only the introduction of the first (loading) dose of Herceptin is accompanied by unpleasant symptoms, and with the introduction of subsequent doses, adverse reactions are already less pronounced or practically absent.
Herceptin is highly regarded not only by breast cancer patients, but also by doctors.
Price for Herceptin in pharmacies
The approximate price for Herceptin in the form of a lyophilisate for the preparation of solution for infusion is 13,360-22,800 rubles. It is possible to purchase a lyophilisate for preparing a concentrate for preparing a solution for infusion for an average of 33,000 - 45,600 rubles. The cost of a solution for subcutaneous administration varies from 33,500 to 43,500 rubles.
Herceptin: prices in online pharmacies
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Drug name Price Pharmacy |
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Herceptin 150 mg lyophilisate for preparation of solution for infusion 1 pc. RUB 9998 Buy |
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Herceptin 440 mg lyophilisate for the preparation of a concentrate for the preparation of a solution for infusion, complete with a solvent 1 pc. RUB 30,190 Buy |
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Herceptin 600 mg / 5 ml solution for subcutaneous administration 5 ml 1 pc. RUB 48,900 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!
