Gertseptin

Gertseptin – antineoplastic drug on the basis of monoclones.

Form of release and structure

Dosage forms:

• Lyophilisate for preparation of solution for infusions: powder from light yellow till white color; the recovered solution – colourless or light yellow color, transparent or slightly opalescent (in colourless glass bottles, in a cardboard pack 1 bottle);
• Lyophilisate for preparation of a concentrate for preparation of solution for infusions: powdery weight from light yellow till white color; the recovered solution – transparent or slightly opalescent from colourless till light yellow color (in colourless glass bottles, in a cardboard pack 1 bottle complete with solvent);
• Solution for hypodermic (п / to) introductions: transparent or opalescent liquid, colourless or yellowish (on 5 ml in colourless glass bottles, in a cardboard pack 1 bottle).

Active ingredient of Gertseptin – трастузумаб:

• 1 bottle with lyophilisate for preparation of solution for infusions – 150 mg;
• 1 bottle with lyophilisate for preparation of a concentrate for preparation of solution for infusions – 440 mg;
• 1 bottle with solution for п / to introduction – 600 mg.

Auxiliary components:

• Lyophilisate for preparation of solution for infusions: α,α - trehaloses a dihydrate, a L-histidine a hydrochloride, polysorbate 20, a L-histidine;
• Lyophilisate for preparation of a concentrate for preparation of solution for infusions: A L-histidine, α,α - trehaloses a dihydrate, a L-histidine a hydrochloride, polysorbate 20;
• Solution for п / to introduction: polysorbate 20, recombinant human hyaluronidase (rHuPH20), a hydrochloride L-histidine monohydrate, L-methionine, α,α-трегалозы a dihydrate, a L-histidine, water for injections.

Solvent: benzyl alcohol, water for injections.

Indications to use

Gertseptin's use is shown at treatment of a metastatic breast cancer with a tumoral hyper expression of HER2:

• Monotherapy (after one or several schemes of chemotherapy);
• The combined treatment with dotsetaksely or paklitaksely (in the absence of the previous first line of chemotherapy);
• The combined treatment with inhibitors of aromatase of women in a postmenopause with positive hormonal receptors (estrogenic and/or progesteronovy).

All forms of drug are appointed at an early stage of a breast cancer with HER2 hyper expression:

• Adjuvant therapy after surgical intervention, end of neoadjuvant or adjuvant chemotherapy, radiation therapy;
• Combination with dotsetaksely or the paklitaksely ambassador of adjuvant chemotherapy cyclophosphamide and doxorubicine;
• Combination with dotsetaksely and karboplatiny at adjuvant chemotherapy;
• Combination with neoadjuvant chemotherapy and the subsequent adjuvant monotherapy by Gertseptin at the tumor size more than 2 cm in the diameter or a locally-spread disease, including an inflammatory form.

Besides, use of two forms of lyophilisate is shown at treatment of a widespread adenocarcinoma of esophageal and gastric transition or a stomach with HER2 hyper expression. Drug appoint along with kapetsitabiny or intravenous (in/in) introduction of a ftoruratsil and drug of platinum (in the absence of the previous antineoplastic therapy concerning a metastatic disease).

Contraindications

• The heavy asthma at rest demanding a maintenance therapy oxygen or caused by metastasises in lungs;
• Age up to 18 years;
• Period of pregnancy and breastfeeding;
• Hypersensitivity to drug components.

With care it is necessary to appoint Gertseptin at coronary heart disease, the arterial hypertension, heart failure, associated diseases of lungs or metastasises in lungs preceding therapy by cardiotoxic medicines (anthracyclines, cyclophosphamide).

Besides, for п / to introduction it is contraindicated to apply solution at early stages of a breast cancer at patients at stenocardia, a myocardial infarction in the anamnesis, chronic heart failure (the II-IV functional class on NYHA), a cardiomyopathy, the fraction of emission of a left ventricle (FELV) less than 55%, clinically significant heart diseases, arrhythmia, uncontrollable arterial hypertension, hemodynamically significant pericardiac exudate, at simultaneous use as a part of adjuvant therapy with anthracyclines.

With care appoint solution for п / to introduction to patients with FVLZh less than 50%, sick advanced age.

Route of administration and dosage

Both forms of lyophilisate enter only intravenously kapelno.

Gertseptin in the form of solution enter п / to.

Use of drug is shown only in the conditions of a hospital under observation of the doctor having experience of use of cytotoxic chemotherapy.

Prior to use it is necessary to hold testing for a tumoral expression of HER2.

Side effects

• New growths of the high-quality, malignant, not specified character (including polyps and cysts): it is unknown – progressing of a new growth, progressing of a malignant new growth;
• Infections and parasitic pathologies: often – cystitis, neytropenichesky sepsis, Herpes zoster, sinusitis, flu, infections of skin, an upper respiratory tract infection, rhinitis, infections of urinary tract, phlegmon, an ugly face; infrequently – sepsis;
• Lymphatic system and system of a hemopoiesis: very often – a febrile neutropenia; it is unknown – a prothrombinopenia;
• Cardiovascular system: very often – disturbance of a cordial rhythm, increase and a lowering of arterial pressure (ABP), heartbeat, trembling of ventricles or auricles, inflows, downgrade of fraction of emission of a left ventricle; often – congestive heart failure, a cardiomyopathy, a supraventricular tachyarrhythmia, a vazodilatation, arterial hypotension; infrequently – a pericardiac exudate; it is unknown – a pericardis, cardiogenic shock, a cantering rhythm, bradycardia;
• Immune system: often – hypersensitivity reactions; it is unknown – anaphylactic reactions and/or shock;
• Mental disorders: often – a depression, alarm, disturbance of thinking;
• Metabolism: often – anorexia, weight reduction of a body; it is unknown – a hyperpotassemia;
• Nervous system: very often – dizziness, a tremor, headaches; often – a muscle hyper tone, a peripheral neuropathy, an ataxy, drowsiness; seldom – paresis; it is unknown – wet brain;
• Sense bodys: very often – the raised slezootdeleniye, conjunctivitis; often – a xerophthalmus; infrequently – deafness; it is unknown – a retinal apoplexy, a papilledema;
• Respiratory system, bodies of a mediastinum and thorax: very often – cough, rattles, nasal bleeding, a rhinorrhea, an asthma; often – functional disturbances of lungs, bronchial asthma; seldom – a pneumonitis; it is unknown – respiratory insufficiency, pulmonary fibrosis, an acute fluid lungs, infiltration of lungs, an acute respiratory distress syndrome, a hypoxia, a bronchospasm, decrease in saturation of hemoglobin oxygen, hypostasis of a lung, an orthopnea, throat hypostasis;
• Alimentary system: very often – diarrhea, nausea, vomiting, abdominal pains, hypostasis of lips; often – dryness in a mouth, pancreatitis, hepatitis, pain in a liver, hepatocellular disturbance, hemorrhoids; seldom – jaundice; it is unknown – a liver failure;
• Dermatological reactions: very often – rash, a face edema, an erythema; often – an itch, a xeroderma, a hyperhidrosis, an acne, an ecchymoma, makulopapulezny rash; it is unknown – a Quincke's disease;
• Musculoskeletal system and connecting fabrics: very often – a mialgiya, muscular constraint, an arthralgia; often – spasms of muscles, dorsodynias, arthritis, pain in a neck, an ossalgiya;
• Kidneys and urinary tract: often – a disease of kidneys; it is unknown – a glomerulonefropatiya, a hymenoid glomerulonephritis, a renal failure;
• Generative organs and mammary glands: often – an inflammation of a mammary gland or mastitis;
• Influence on the course of pregnancy, puerperal and perinatal states: it is unknown – a fatal hypoplasia of kidneys and a hypoplasia of lungs at a fruit, олигогидрамнион;
• Others: very often – stethalgias, a fever, weakness, an adynamy, a grippopodobny syndrome, pains, fever, reactions connected with administration of drug; often – hypostases, an indisposition, a bruise.

The most frequent and dangerous undesirable reactions of use of Gertseptin:

• The reactions caused by administration of drug or reaction of hypersensitivity: a respiratory distress syndrome, nausea, an asthma, a fever and/or fever, rash, tachycardia, arterial hypotension, a bronchospasm, rattles in lungs, decrease in saturation of hemoglobin oxygen, vomiting, a headache; local reactions – reddening, hypostasis, an itch, rash in an injection site;
• Cardiotoxicity: often – the heart failure (the II-IV functional class on NYHA) associating with a fatal outcome. At use of a trastuzumab in a combination with adjuvant chemotherapy the frequency of symptomatic congestive heart failure does not differ from that when receiving only chemotherapy and is slightly higher at use of taxons and Gertseptin consistently. Safety of resuming or continuation of therapy at the phenomena of cardiotoxicity is not studied, for improvement of a condition of patients purpose of the standard therapy including cardiac glycosides, diuretics, beta adrenoblockers and/or inhibitors of an angiotensin-converting enzyme is recommended. In most cases at clinical signs of advantage of drug therapy is continued without emergence of clinically significant additional cardial phenomena;
• Disturbances from lungs: infiltrates in lungs, pneumonia, an acute respiratory distress syndrome, a pneumonitis, a pleural exudate, respiratory insufficiency, an acute fluid lungs and other heavy complications from lungs, including with a lethal outcome;
• Hematologic toxicity: very often – a febrile neutropenia; often – anemia, a leukopenia, thrombocytopenia, a neutropenia; it is unknown – a prothrombinopenia. The risk of a neutropenia is slightly higher at a combination with the dotsetaksely ambassador of anthracycline therapy.

Besides, Gertseptin's use causes side effects characteristic of each of dosage forms of drug.

Lyophilisate for preparation of solution for infusions and lyophilisate for preparation of a concentrate for preparation of solution for infusions

• Infectious and parasitic pathologies: often – infections, pneumonia, a nasopharyngitis;
• Lymphatic system and system of a hemopoiesis: often – a neutropenia, a leukopenia, anemia, thrombocytopenia;
• Mental disturbances: often – sleeplessness;
• Nervous system: often – paresthesias, a dysgeusia;
• Respiratory system, bodies of a mediastinum and thorax: often – pharyngitis; infrequently – a pleural exudate;
• Alimentary system: often – a lock, pancreatitis, dyspepsia;
• Dermatological reactions: often – an alopecia, disturbance of structure of nails; it is unknown – urticaria, dermatitis;
• Others: often – mukozit, peripheral hypostases.

Solution for п / to introduction

• Infectious and parasitic pathologies: very often – infections, a nasopharyngitis; often – pharyngitis;
• Lymphatic system and system of a hemopoiesis: very often – thrombocytopenia, a neutropenia, a leukopenia, anemia; it is unknown – immune thrombocytopenia;
• Mental disturbances: very often – sleeplessness;
• Nervous system: very often – a dysgeusia, paresthesias;
• Respiratory system: very often – pneumonia; often – a pleural exudate; it is unknown – an intersticial pulmonary disease;
• Alimentary system: very often – stomatitis, dyspepsia, a lock;
• Dermatological reactions: very often – disturbance of structure of nails, an alopecia, a palmar and bottom syndrome; often – an onikhoklaziya, dermatitis; infrequently – a small tortoiseshell;
• Musculoskeletal system: often – extremity pains;
• Others: very often – mukozit, peripheral hypostases.

Besides, frequent and dangerous undesirable reactions against the background of use of solution for п / to introduction:

• Infections: infection of postoperative wounds, acute pyelonephritis, respiratory infections, sepsis;
• Increase in the ABP: to a thicket at patients with arterial hypertension in the anamnesis.

Special instructions

The drug is administered at observance of aseptic conditions.

Before introduction surely it is necessary to check marking and to be convinced of compliance of a dosage form to appointment – for in/in drop or п / to introduction.

It is impossible to enter Gertseptin in the form of lyophilisate in/in bolyusno or struyno, solution for п / to introduction – in / century.

Solution for п / to introduction – drug, ready to use, it cannot be mixed with other medicines. Before use it is necessary to be convinced of lack of mechanical impurity and changes of coloring of solution.

It is necessary to specify the trade name and number of a series of drug in a medical card of the patient. Only the attending physician can make replacement of drug by other biological means.

HER2 testing is made only in the specialized laboratory capable to provide quality of the procedure of testing.

Gertseptin is shown at a breast cancer in a metastatic or early stage only with a tumoral hyper expression of HER2, lyophilisate is also applied at a metastatic carcinoma of the stomach with a tumoral hyper expression of HER2 established with use of exact and validirovanny methods of definition.

Prior to use of drug it is necessary to compare potential advantage and risk of treatment.

At purpose of drug, especially in case of the previous therapy by means of an anthracycline row and the cyclophosphamide sick careful cardiological inspection with collecting the anamnesis, passing of physical survey, the electrocardiogram, an echocardiography and/or radio isotope ventrikulografiya or magnetic and resonant tomography is necessary.

Treatment should be accompanied regular (1 time in 3 months) with monitoring of function of heart, and at asymptomatic dysfunction of heart – every 1,5-2 month. Cardiological examination is conducted 1 time in 6 months within 24 months after the end of administration of drug.

At a metastatic breast cancer Gertseptin in a combination with anthracyclines is not recommended to appoint.

Infusional reactions can arise both at administration of drug, and several hours later after infusion. At their emergence it is necessary to stop introduction and to watch carefully the patient before full elimination of symptoms.

The heavy complications connected with pulmonary disturbances can be followed by a lethal outcome therefore patients with risk factors have to be under constant observation of the doctor. With care enter Gertseptin at earlier carried out or accompanying therapy by other anti-neoplastic means (radiation therapy, gemcitabine, taxons, винорельбин).

Neoadjuvant-adjuvant therapy is not recommended to patients 65 years in connection with limitation of clinical experience are more senior.

For decrease in risk of development of undesirable reactions to administration of drug it is possible to use premedication. Reception of analgetics antipyretics, including paracetamol, or antihistamines is shown (дифенгидрамин). Reactions at in introduction successfully are suppressed with use of inhalations of oxygen, beta адреностимуляторов, glucocorticosteroids.

At emergence of undesirable reactions against the background of administration of drug, the patient should not manage vehicles and mechanisms.

Medicinal interaction

Gertseptin in the form of lyophilisate is incompatible from 5% dextrose solution, it cannot be dissolved or mixed with other means.

Clinical trials did not note interaction at simultaneous use of a trastuzumab with other drugs.

Terms and storage conditions

To protect from children.

To store at a temperature of 2-8 °C.

Period of validity: lyophilisate – 48 months, solution – 21 months.