Beiodine

2024 Author: Rachel Wainwright | [email protected]. Last modified: 2023-12-15 07:39

Instructions for use:

1. Release form and composition
2. Indications for use
3. Contraindications
4. Method of application and dosage
5. Side effects
6. Special instructions
7. Drug interactions
8. Terms and conditions of storage

Beiodine is a two-component anticancer drug.

Release form and composition

Beiodine is available as a set of two components:

component No. 1 - Perjeta - concentrate for preparation of solution for infusion: transparent or opalescent, colorless or slightly brownish (in colorless glass vials 420 mg / 14 ml);
component No. 2 - Herceptin - lyophilisate for preparing a concentrate for preparing a solution for infusion: from light yellow to white; the reconstituted solution is a clear or slightly opalescent liquid from light yellow to colorless; solvent - bacteriostatic water for injection - transparent, with a slight yellowish tinge or colorless liquid (in colorless glass vials: drug - 440 mg, solvent - 20 ml).

The Bayodaim set (3 bottles) is placed in a cardboard pallet, 1 pallet in a cardboard box with first opening control.

Composition of 1 bottle (14 ml) Perjets:

active substance: pertuzumab - 420 mg;
auxiliary components: glacial acetic acid - 9.2 mg, L-histidine - 43.5 mg, polysorbate 20 - 2.8 mg, sucrose - 575.1 mg, water for injection - up to 14 ml.

Composition of 1 bottle of Herceptin:

active substance: trastuzumab - 440 mg;
auxiliary components: α, α-trehalose dihydrate - 400 mg, polysorbate 20 - 1.8 mg, L-histidine - 6.4 mg, L-histidine hydrochloride - 9.9 mg.

The composition of 1 bottle of Herceptin solvent: benzyl alcohol (as an antimicrobial preservative) - 229.9 mg, water for injection - 20.9 ml.

Indications for use

Beiodine is used in combination with docetaxel to treat the following conditions:

metastatic breast cancer: metastatic or locally recurrent, inoperable breast cancer with tumor overexpression of HER2 (human epidermal growth factor receptor type II) in the absence of previous HER2-specific treatment or chemotherapy for metastatic disease;
neoadjuvant therapy for breast cancer: locally advanced, edematous-infiltrative or early breast cancer (with a tumor diameter greater than 2 cm) with overexpression of HER2 as part of a therapy regimen containing carboplatin or FEC (fluorouracil, epirubicin and cyclophosphamide).

Contraindications

Absolute:

LVEF (left ventricular ejection fraction) before treatment <50%;
functional disorders of the liver (the safety profile for this group of patients has not been studied);
uncontrolled arterial hypertension;
previous therapy with anthracyclines with a cumulative dose of doxorubicin or an equivalent drug> 360 mg / m ²;
burdened history of chronic heart failure;
recent myocardial infarction;
severe dyspnea at rest, associated with lung metastases or requiring maintenance oxygen therapy;
serious cardiac arrhythmias that require drug therapy at the time of administration of Beiodine, except for paroxysmal supraventricular tachycardia and atrial fibrillation;
age up to 18 years (the safety profile for this group of patients has not been studied);
pregnancy and the period of breastfeeding (lactation);
hypersensitivity to drug components or mouse protein.

Relative (Beiodine is prescribed with caution in the presence of the following diseases / conditions):

decrease in LVEF to <50% during previous adjuvant therapy with Herceptin;
LVEF values <55%;
conditions that can disrupt the function of the left ventricle;
concomitant lung diseases or metastases to the lungs;
functional disorders of the kidneys;
previous therapy with cardiotoxic drugs, including anthracyclines / cyclophosphamides, or previous radiation therapy to the chest area;
arterial hypertension;
heart failure;
coronary heart disease.

Method of administration and dosage

Tests for tumor expression of HER2 are performed prior to the appointment of Beiodine. The mandatory criteria for therapy include: the result of immunohistochemical analysis (IHC) - 3+ points and / or the result of in situ hybridization (ISH) - the degree of amplification ≥2.0. Test methods must be accurate and validated.

Beiodine components are administered only by intravenous (intravenous) drip. IV jet or bolus administration is prohibited.

The sequence of administration of the components of the drug does not matter. In cases where premedication is required before the introduction of Herceptin, it is administered first. After each use of Perjeta and until the moment of administration of Herceptin or docetaxel, it is recommended to monitor the patient's condition for 30-60 minutes. Docetaxel is recommended to be administered last.

Dosing regimen:

Perjeta: The first dose is administered over 60 minutes. If well tolerated, subsequent infusions can be carried out within 30-60 minutes. Loading dose - 840 mg, maintenance (administered 3 weeks after loading) - 420 mg every 3 weeks;
Herceptin: The first dose is given over 90 minutes. If well tolerated, subsequent infusions can be carried out within 30 minutes. Loading dose - 8 mg / kg, maintenance (administered 3 weeks after loading) - 6 mg / kg every 3 weeks;
docetaxel: the initial dose is 75 mg / m ², then the same dose is administered every 3 weeks. If the drug is well tolerated in the first cycle, the dose can be further increased to 100 mg / m ².

In neoadjuvant therapy for breast cancer, Bayodaim in combination with docetaxel is prescribed prior to surgery (dosage regimen is described above).

One of three treatment regimens for early breast cancer is possible:

Beiodine in combination with docetaxel - 4 cycles, then postoperative FEC therapy - 3 cycles;
preoperative therapy with FEC - 3 cycles, then Bayodaim in combination with docetaxel - 3 cycles;
Beiodine in combination with docetaxel and carboplatin (it is not recommended to increase the dose of docetaxel above 75 mg / m ²) - 6 cycles.

After the surgical operation, Herceptin therapy should be continued, the total duration of its use is 1 year.

The combined use of Perjeta with anthracyclines is not recommended (due to insufficient data).

Duration of treatment:

neoadjuvant therapy for breast cancer: for 3, 4 or 6 cycles (depending on the chosen therapy regimen);
metastatic breast cancer: until signs of disease progression or unacceptable toxicity appear.

It is not recommended to reduce the dose of each of the components of Bayodaim. If one of the components is canceled, therapy is stopped completely.

If docetaxel is discontinued, treatment of metastatic breast cancer with Bayodaim can be continued until the disease progresses or unacceptable toxicity occurs.

During the development of chemotherapy-induced reversible myelosuppression, therapy can be continued with careful control of complications due to neutropenia.

The use of Bayodaim is suspended for at least 3 weeks in the following cases:

LVEF values of 40–45% with a decrease in LVEF by ≥10% compared to the values observed before starting therapy;
lowering LVEF to below 40%.

In cases of development of an infusion reaction, it is necessary to reduce the infusion rate or temporarily interrupt the administration of the solution.

If serious hypersensitivity reactions appear, therapy is completely stopped.

Dilution of the Bayodaim components is carried out in separate infusion bags made of polyvinyl chloride (PVC), polyolefin and polyethylene. The components are incompatible with 5% dextrose solution. It is impossible to mix or dilute them together with other medicines. Preparation of the drug for administration should be carried out under aseptic conditions.

Features and method of dilution of components:

Perjeta: can only be diluted in 0.9% sodium chloride solution; the bottle is for single use. For dilution, the entire liquid concentrate is taken from the vial and injected into an infusion bag with a 0.9% sodium chloride solution of 250 ml. The concentration of the finished solution: loading dose - 3.36 mg / ml (840 mg / 250 ml), maintenance dose - 1.68 mg / ml. After reconstitution, the bag is gently inverted to mix (foaming should be avoided). The solution is introduced immediately after preparation. In exceptional cases, it can be stored for up to 24 hours at a temperature of 2–8 ° C;
Herceptin: the contents of the vial are dissolved in 20 ml bacteriostatic water for injection (supplied in the kit). The resulting solution concentrate is suitable for repeated use. Its concentration is 21 mg / ml, pH is 6.0. When dissolving, avoid excessive foaming. The concentrate is stable for 28 days at 2–8 ° C. The use of sterile water for injection (without preservative) is acceptable as a solvent. It is not recommended to use other solvents. To prepare the infusion solution, the corresponding volume of the concentrate is injected into the infusion bag with a 0.9% sodium chloride solution of 250 ml. The infusion solution is administered immediately after its preparation. In exceptional cases, it can be stored for no longer than 24 hours at a temperature of 2–8 ° C.

Side effects

Metastatic breast cancer

The most common adverse reactions (more than 50% of cases) are diarrhea, neutropenia, and alopecia.

The most common (more than 10% of cases) disorders of III-IV severity according to the National Cancer Institute Common Terminology Criteria of Adverse Events (NCI-CTCAE), version 3.0 are neutropenia, leukopenia and febrile neutropenia.

The most severe and clinically significant disorder (less than 10% of cases) is left ventricular dysfunction, including symptomatic left ventricular systolic dysfunction (chronic heart failure).

The incidence of side effects after discontinuation of docetaxel decreases, except for such as upper respiratory tract infections, rash, diarrhea, headache, itching, nasopharyngitis, nausea, asthenia, arthralgia and fatigue.

Neoadjuvant Breast Cancer Therapy

The incidence of adverse reactions depending on the treatment regimen:

Beiodine in combination with docetaxel - 4 cycles, then postoperative FEC therapy - 3 cycles: ≥50% - alopecia and neutropenia; ≥10% - neutropenia;
preoperative therapy of FEC - 3 cycles; then Bayodaim in combination with docetaxel - 3 cycles: ≥50% - diarrhea, alopecia, nausea; ≥10% - leukopenia, neutropenia;
Beiodine in combination with docetaxel and carboplatin - 6 cycles: ≥50% - alopecia, diarrhea; ≥10% - neutropenia, anemia, febrile neutropenia, diarrhea, leukopenia.

Metastatic Breast Cancer and Neoadjuvant Breast Cancer Therapy

Possible violations during combined treatment (very often - ≥1 / 10; often - ≥1 / 100 and <1/10; infrequently - ≥1 / 1000 and <1/100; rarely - ≥1 / 10,000 and <1 / 1000; very rarely - <1/10 000, taking into account isolated cases; with an unknown frequency - if it is impossible to estimate the frequency of development; it should be borne in mind that it is problematic to establish a causal relationship between a specific drug and an adverse event):

cardiovascular system: often - left ventricular dysfunction; infrequently - chronic heart failure;
hematopoietic system: very often - neutropenia, leukopenia, anemia, febrile neutropenia (possibly fatal);
digestive system: very often - vomiting, decreased appetite, nausea, diarrhea, stomatitis, constipation, dyspeptic symptoms;
respiratory system: very often - cough; often pleural effusion, shortness of breath; infrequently - interstitial lung disease;
musculoskeletal system: very often - arthralgia, myalgia;
immune system: very often - anaphylactic reactions / hypersensitivity, cytokine release syndrome / infusion reactions;
nervous system: very often - headache, peripheral neuropathy, dysgeusia; often - dizziness;
psyche: very often - insomnia;
organ of vision: often - increased lacrimation;
skin and subcutaneous tissues: very often - rash, alopecia, nail pathology; often - dry skin, itching, paronychia;
others: very often - peripheral edema, increased fatigue, pain, asthenia, inflammation of the mucous membranes of various localization, increased body temperature, the addition of secondary infections; often - chills.

Disorders that develop with the use of Herceptin for all approved indications, in regimes that differ from the regime of use of Bayodaim in combination with docetaxel (the classification of the frequency of development corresponds to the above; due to the fact that Herceptin is often used simultaneously with chemotherapy drugs, as well as after completion of the course of radiation therapy, it is problematic to determine the causal relationship):

nervous system: very often - dizziness, tremors, headaches; often - paresthesia, peripheral neuropathy, drowsiness, muscle hypertonia, dysgeusia, ataxia; rarely - paresis; with an unknown frequency - cerebral edema;
hematopoietic system: very often - leukopenia, anemia, febrile neutropenia, neutropenia; often - thrombocytopenia; with an unknown frequency - hypoprothrombinemia;
immune system: often - hypersensitivity reactions; with an unknown frequency - anaphylactic shock, anaphylactic reactions;
respiratory system: very often - nosebleeds, wheezing, cough, shortness of breath, rhinorrhea; often - impaired lung function, bronchial asthma, pharyngitis; infrequently - pleural effusion; rarely - pneumonitis; with an unknown frequency - hypoxia, lung infiltration, pulmonary fibrosis, acute pulmonary edema, respiratory failure, acute respiratory distress syndrome, bronchospasm, decreased hemoglobin oxygen saturation, orthopnea, laryngeal and pulmonary edema;
cardiovascular system: very often - a decrease in the left ventricular ejection fraction, a decrease and increase in blood pressure, palpitations, heart rhythm disturbances, flutter, hot flashes; often - heart failure, vasodilation, supraventricular tachyarrhythmia, arterial hypotension, cardiomyopathy; infrequently - pericardial effusion; with an unknown frequency - gallop rhythm, pericarditis, cardiogenic shock, bradycardia;
digestive system: very often - dyspepsia, abdominal pain, diarrhea, vomiting, lip swelling, nausea, constipation; often - hepatitis, anorexia, soreness in the liver, pancreatitis, dry mouth, hemorrhoids, hepatocellular damage; rarely, jaundice; with an unknown frequency - hepatic failure;
urinary system: often - kidney disease; with an unknown frequency - glomerulonephropathy, membranous glomerulonephritis, renal failure;
musculoskeletal system: very often - muscle stiffness, arthralgia, myalgia; often - muscle spasms, arthritis, ossalgia, pain in the back, limbs and neck;
skin and subcutaneous tissues: very often - violation of the structure of the nails, erythema, rash, alopecia, swelling of the face; often - acne, hyperhidrosis, ecchymosis, dry skin, dermatitis, maculopapular rash, onychoclasia, pruritus, urticaria; with an unknown frequency - angioedema;
metabolism: with an unknown frequency - hyperkalemia;
psyche: often - thinking disorders, anxiety, insomnia, depression;
organ of sight and hearing: very often - increased lacrimation, conjunctivitis; often dry eyes; infrequently - deafness; with an unknown frequency - retinal hemorrhage, edema of the optic nerve head;
neoplasms (malignant, benign and unspecified, including polyps and cysts): with an unknown frequency - the progression of neoplasms / malignant neoplasms;
parasitic / infectious diseases: often - neutropenic sepsis, pneumonia, cystitis, phlegmon, Herpes zoster, influenza, nasopharyngitis, sinusitis, rhinitis, erysipelas, infections of the skin, upper respiratory and urinary tract; infrequently - sepsis;
pregnancy, postpartum / perinatal period: with unknown frequency - oligohydramnios, fatal pulmonary hypoplasia and impaired renal function and / or renal hypoplasia in the fetus;
genitals and mammary gland: often - mastitis / inflammation of the mammary glands;
others: very often - infusion reactions, chest pain, asthenia, chills, flu-like syndrome, fever, weakness, pain, mucositis; often - peripheral edema, weight loss, malaise, bruise, edema.

special instructions

The patient's medical records must indicate the trade name of the Bayodaim set. When replacing the kit components with any other biological preparations with a similar effect, it is necessary to consult with the doctor who prescribed the therapy. Care should be taken with such a replacement in the absence of data that confirm interchangeability.

Beiodine can be used only under the supervision of an experienced doctor; medical personnel should carry out infusions.

In the presence of hypersensitivity to benzyl alcohol, Herceptin should be dissolved with water for injection. In such cases, only 1 dose can be taken from each vial. The remaining solution must be destroyed.

If, during therapy, disorders such as dizziness and infusion reactions develop, you should refuse to drive vehicles until the symptoms disappear completely.

Drug interactions

Signs of pharmacokinetic interaction of Perjeta with Herceptin, docetaxel, erlotinib, gemcitabine, capecitabine were not found.

In clinical studies, no significant interaction of Herceptin with drugs used in combination with it was noted.

Terms and conditions of storage

Store in a dark place, out of reach of children, at a temperature of 2-8 ° C.

Shelf life is 2 years.

Information about the drug is generalized, provided for informational purposes only and does not replace the official instructions. Self-medication is hazardous to health!