Acellbia - Instructions For Use Of The Drug, Price, Reviews, Analogues

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

Acellbia

Acellbia: instructions for use and reviews

1. 1. Release form and composition
2. 2. Pharmacological properties
3. 3. Indications for use
4. 4. Contraindications
5. 5. Method of application and dosage
6. 6. Side effects
7. 7. Overdose
8. 8. Special instructions
9. 9. Application during pregnancy and lactation
10. 10. Use in childhood
11. 11. Use in the elderly
12. 12. Drug interactions
13. 13. Analogs
14. 14. Terms and conditions of storage
15. 15. Terms of dispensing from pharmacies
16. 16. Reviews
17. 17. Price in pharmacies

Latin name: Acellbia

ATX code: L01XC02

Active ingredient: rituximab (Rituximab)

Manufacturer: Biocad CJSC (Russia)

Description and photo updated: 2019-27-08

Prices in pharmacies: from 10,000 rubles.

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Acellbia is an antineoplastic drug.

Release form and composition

Dosage form - concentrate for the preparation of solution for infusion: clear liquid from colorless to light yellow (in glass colorless vials, sealed with rubber stoppers with rolling aluminum caps: 10 ml each - 2 pcs. In a blister strip, in a cardboard box 1 package; 30 ml or 50 ml - in a cardboard box 1 bottle; each pack also contains instructions for the use of Acellbia).

1 ml of concentrate contains:

• active substance: rituximab - 10 mg;
• auxiliary components: polysorbate 80, sodium citrate dihydrate, hydrochloric acid, sodium chloride, water for injection.

Pharmacological properties

Pharmacodynamics

The active ingredient of the Acellbia drug, rituximab, is a chimeric mouse / human monoclonal antibody that specifically binds to the CD20 transmembrane antigen. This antigen is located on mature B-lymphocytes and pre-B-lymphocytes, but is absent on normal plasma cells, pro-B-cells, hematopoietic and other tissues. It is expressed in more than 95% of cases with B-cell non-Hodgkin's lymphomas. CD20, expressed on the cell, after binding to rituximab is not internalized and ceases to enter the extracellular space from the cell membrane. CD20 does not circulate in plasma as a free antigen, so it does not compete for antibody binding. By binding to the CD20 antigen on B-lymphocytes, the drug initiates immunological reactions that mediate B-cell lysis. Possible mechanisms of cell lysis are induction of apoptosis, antibody-dependent cellular cytotoxicity, and complement-dependent cytotoxicity.

In vitro Acellbia increases the sensitivity of B-cell lymphoma lines to the cytotoxic effects of certain chemotherapeutic agents.

After the first injection of the drug, the number of B-cells in the peripheral blood decreases below normal. In patients with hematological malignant diseases, it begins to recover after 6 months, reaches normal values 12 months after the end of treatment, but this period may be longer.

Anti-chimeric antibodies were detected in 1.1% of the examined patients with non-Hodgkin's lymphoma. Anti-mouse antibodies were not detected.

Pharmacokinetics

Non-Hodgkin's lymphoma

According to the results of a population pharmacokinetic analysis, in non-Hodgkin's lymphoma after a single and repeated use of rituximab as a monopreparation or in combination with chemotherapy according to the CHOP regimen (cyclophosphamide + hydroxydaunorubicin + vincristine + prednisolone), specific clearance (CL2), and its CLI rituximab the volume of distribution in plasma (VI) is 0.59 l / day, 0.14 l / day and 2.7 l, respectively.

The terminal half-life averages 22 days. When rituximab is administered intravenously at a dose of 375 mg / m ² once a week for 4 weeks, the specific clearance of the drug is affected by the size of the tumor focus and the initial level of CD 19-positive cells. This indicator is the higher, the larger the size of the tumor focus in the patient or the higher the level of CD 19-positive cells. Individual variability in the specific clearance of rituximab persists even after correcting the level of CD 19-positive cells and the size of the tumor focus.

Relatively small changes in the volume of distribution in plasma are influenced by the body surface area (1.53–2.32 m ²) and chemotherapy according to the CHOP scheme, they amount to 27.1% and 19%, respectively.

The general condition of the patient, his age, gender and race do not affect the pharmacokinetic parameters of rituximab, therefore, dose adjustment of Acellbia, depending on these factors, is not required.

The average maximum concentration (Cmax) increases after each injection of Acellbia: after the first infusion it is 243 μg / ml, after the fourth - 486 μg / ml, after the eighth - 550 μg / ml. The minimum and maximum concentrations of rituximab are inversely related to the initial number of CD 19-positive B cells and the magnitude of the tumor load.

If the therapy is effective, the median equilibrium concentration rises. This figure is higher in patients with histological tumor subtypes B, C, and D [according to the International Working Formulation (IWF)] than in subtype A. Traces of rituximab can be found in the body for 3-6 months after the last injection of Acellbia.

The pharmacokinetic profile of rituximab monotherapy and combination therapy (6 infusions of rituximab at 375 mg / m ²and 6 cycles of CHOP chemotherapy) is almost comparable. In accordance with the data of our own comparative study of the pharmacokinetics of the drug in patients with low-grade non-Hodgkin's lymphoma, the AUC (area under the concentration-time curve) in the Acellbia group was 16 170.57 (μg / ml) × h, in the drug use group MabThera - 17,608.42 (μg / ml) × h, rituximab clearance was 43.87 ml / (h × kg) and 43.17 ml / (h × kg), respectively. Cmax of Acellbia - 172.19 μg / ml, the time to reach it - 31.17 h, in the MabThera group the same indicators were 190.68 μg / ml and 37.47 h, respectively. The half-life in the Acellbia group was 49.60 h, in the Mabthera group - 48.95 hours. The ratio of the geometric mean Cmax of Acellbia and Mabthera is 81.82-115.82%, the ratio of the geometric mean AUC _0-168 Acellbia and Mabthera - 80.13–118.18%, which indicates the equivalence of the pharmacokinetic parameters of both drugs when administered intravenously.

Chronic lymphocytic leukemia

After the fifth infusion of the drug at a dose of 500 mg / m ^{2, the} average maximum concentration is 408 μg / ml.

Indications for use

The use of Acellbia is indicated for the treatment of non-Hodgkin's lymphomas:

• treatment of recurrent or chemoresistant B-cell, CD20-positive, low-grade or follicular non-Hodgkin's lymphoma;
• maintenance therapy of follicular lymphoma following response to induction therapy;
• combination therapy of stage III – IV follicular lymphoma with chemotherapy in previously untreated patients;
• combination therapy of CD20-positive diffuse large B-cell lymphoma with chemotherapy according to the CHOP regimen.

In addition, Acellbia is prescribed for chronic lymphocytic leukemia:

• simultaneous use with chemotherapy in patients who have not previously received standard therapy;
• a relapsing or chemoresistant form, in combination with chemotherapy.

Contraindications

• severe primary or secondary immunodeficiency;
• acute infectious diseases;
• the period of pregnancy and breastfeeding;
• age up to 18 years;
• hypersensitivity to mouse proteins;
• individual intolerance to the components of the drug.

Acellbia should be used with caution in patients with tumor infiltration of the lungs, a history of respiratory failure, chronic infections, with a high tumor load or the number of circulating malignant cells exceeding 25,000 per μl, with neutropenia (less than 1500 per μl), thrombocytopenia (less 75,000 per μL).

Acellbia, instructions for use: method and dosage

The ready-made Acellbium solution is intended only for intravenous (IV) drip administration through a separate catheter!

Do not inject the solution into / in bolus or jet!

Preparation of the solution should be carried out under aseptic conditions before direct use.

It is necessary to collect the required amount of concentrate and dilute in an infusion bottle or bag to the calculated concentration (1–4 mg per 1 ml) with 0.9% sodium chloride infusion solution or 5% dextrose solution. The solutions used must be pyrogen-free and sterile. Mixing should be done by gently inverting the bottle or bag to prevent foam formation.

Before administration, the solution should be inspected for color changes or the presence of impurities.

The doctor needs to monitor the correct preparation, compliance with the conditions and storage time of the finished solution before use.

Physically and chemically, the infusion solution remains stable at room temperature for 12 hours, at a temperature of 2-8 ° C - no more than 24 hours.

It is recommended to start the first infusion at a rate of 50 mg per hour, then every 0.5 hours it can be increased by 50 mg per hour, bringing to a maximum rate of 400 mg per hour. The second and subsequent infusions can be started at a rate of 100 mg per hour, increasing it every 0.5 hours by 100 mg per hour until a maximum rate of 400 mg per hour is reached.

It is not recommended to reduce the dose of Acellbia; when used in combination with chemotherapy, the dose of chemotherapy is reduced in accordance with standard recommendations.

Each infusion should be administered with premedication with analgesics or antipyretics (including paracetamol), antihistamines (including diphenhydramine). In the absence of glucocorticosteroids (GCS) as part of combination therapy with chemotherapy drugs, GCS is also included in the premedication.

Recommended standard dosing regimen of Acellbia for low-grade or follicular non-Hodgkin's lymphoma:

• initial therapy: monotherapy - at the rate of 375 mg per 1 m ² of the patient's body surface once a week, the course of treatment is 4 weeks; combination therapy with chemotherapy - at the rate of 375 mg 1 m ²on the first day of the chemotherapy cycle after preliminary intravenous administration of GCS as a component of therapy. The course of treatment is carried out according to one of the following schemes: 8 cycles (1 cycle lasts 2 weeks) - with the R-CVP scheme, which includes rituximab, vincristine, prednisolone, cyclophosphamide; 8 cycles (cycle 4 weeks) - with the R-MCP scheme (mitoxantrone, chlorambucil, rituximab, prednisolone); 8 cycles (cycle 3 weeks) - with the R-CHOP scheme (cyclophosphamide, doxorubicin, rituximab, prednisolone, vincristine), upon reaching complete remission after the fourth cycle, you can limit yourself to six cycles; 6 cycles (cycle 3 weeks) - with the R-CHVP-Interferon scheme (rituximab, doxorubicin, teniposide, cyclophosphamide, prednisolone, interferon);
• repeated use in patients with a response to the first course of therapy in case of relapse: 375 mg per 1 m ² once a week, the course of treatment is 4 weeks;
• maintenance therapy after response to induction therapy: in previously untreated patients - 375 mg per 1 m ² once every 8 weeks, the course of therapy - no more than 12 infusions (therapy should be discontinued if signs of disease progression appear); recurrent or chemoresistant lymphoma - 375 mg per 1 m ² once every 12 weeks, no more than 8 infusions (therapy is stopped if signs of disease progression appear).

Combined treatment of diffuse large B-cell non-Hodgkin's lymphoma with chemotherapy according to the CHOP scheme consists in the introduction on the first day of each chemotherapy cycle after intravenous administration of corticosteroids at a dose of 375 mg per 1 m ², then other components of the CHOP scheme (vincristine, cyclophosphamide, doxorubicin). The course of treatment is 8 cycles.

In the treatment of chronic lymphocytic leukemia in combination with chemotherapy in patients receiving standard therapy for the first time, and in the case of recurrent or chemo-resistant lymphocytic leukemia, the following doses of Acellbia are used: on the first day of the first cycle - 375 mg per 1 m ² of body surface, then on the first day of each next cycle - 500 mg per 1 m ². The drug is administered before chemotherapy. The course of treatment is 6 cycles.

To reduce the risk of developing tumor lysis syndrome, the patient, as a preventive measure, must ensure adequate hydration and the introduction of uricostatics 48 hours before the start of treatment. Patients with chronic lymphocytic leukemia and a lymphocyte count of more than 25,000 in 1 μl are recommended to inject 100 mg of prednisone or prednisolone 1 hour before the IV infusion of rituximab. This will reduce the severity and frequency of cytokine release syndrome and / or acute infusion reactions.

No dose adjustment of Acellbia is required in elderly patients (65 years and older).

Side effects

Side effects of monotherapy or maintenance therapy for low-grade or follicular non-Hodgkin's lymphoma:

• parasitic and infectious pathologies: very often - viral and bacterial infections; often - herpes zoster, pneumonia, respiratory tract infections, fungal infections, sepsis, infections of unknown etiology, infections with fever;
• from the blood and lymphatic system: very often - neutropenia, leukopenia; often - anemia, thrombocytopenia; infrequently - blood clotting disorder, lymphadenopathy, hemolytic anemia, transient partial aplastic anemia;
• from the immune system: very often - angioedema; often - hypersensitivity reactions;
• on the part of metabolism and nutrition: often - weight loss, hyperglycemia, facial edema, peripheral edema, hypocalcemia, increased activity of lactate dehydrogenase (LDH);
• from the respiratory system, chest and mediastinal organs: often - cough, rhinitis, chest pain, bronchospasm, shortness of breath, respiratory diseases; infrequently - impaired lung function, hypoxia, bronchial asthma, bronchiolitis obliterans;
• from the gastrointestinal tract: very often - nausea; often - lack of appetite, vomiting, diarrhea, abdominal pain, dyspepsia, dysphagia, stomatitis, sore throat, constipation; infrequently - an increase in the abdomen;
• from the nervous system: often - sleep disturbance, dizziness, hypesthesia, paresthesia, vasodilation, agitation, anxiety; infrequently - perversion of taste;
• on the part of the cardiovascular system: often - lowering blood pressure (BP), orthostatic hypotension, increased blood pressure, tachycardia, atrial fibrillation, arrhythmia, cardiac pathology; infrequently - bradycardia, left ventricular heart failure, supraventricular and ventricular tachycardia, angina pectoris, myocardial ischemia;
• general disorders and local reactions: very often - asthenia, fever, headache, chills; often - weakness, pain in tumor foci, hot flashes, flu-like syndrome; infrequently - pain at the injection site;
• on the part of the musculoskeletal system: often - pain, myalgia, neck pain, arthralgia, back pain, muscle hypertonia;
• mental disorders: infrequently - depression, nervousness;
• from the skin and subcutaneous tissues: very often - rash, itching; often - sweating, urticaria, increased sweating at night, alopecia;
• from the organ of hearing, labyrinth disorders: often - noise and pain in the ears;
• on the part of the organ of vision: often - conjunctivitis, lacrimation disorders;
• laboratory and instrumental data: very often - a decrease in the level of immunoglobulin G (IgG).

Additional adverse reactions in the combined treatment of non-Hodgkin's lymphoma and chronic lymphocytic leukemia with chemotherapy (R-CVP, R-FC, R-CHOP):

• parasitic and infectious pathologies: very often - bronchitis; often - sinusitis, acute bronchitis, primary infection and exacerbation of hepatitis B;
• from the skin and subcutaneous tissues: very often - alopecia; often - skin diseases;
• on the part of the blood and lymphatic system: very often - febrile neutropenia, neutropenia, thrombocytopenia; often - granulocytopenia, pancytopenia;
• general disorders and local reactions: often - chills, fatigue.

In addition, adverse events that occur during rituximab therapy: neutropenic infections, hematotoxicity, urinary tract infections, superinfections of the lungs, septic shock, implant infections, mucous nasal discharge, staphylococcal septicemia, pulmonary edema, sensitivity disorders, heart failure, venous thrombosis, mucositis, deep vein thrombosis of the extremities, decreased ejection fraction of the left ventricle, edema of the lower extremities, fever, bacteremia, deterioration of general health, decompensation of diabetes mellitus, multiple organ failure.

Adverse effects of combination therapy:

• patients aged 65 and older: a higher frequency of side effects (third and fourth degrees of severity) from the lymphatic system and the blood system compared with younger patients when using the drug in the first line of therapy, treatment of recurrent or chemically resistant chronic lymphocytic leukemia;
• high tumor load (diameter of single foci more than 10 cm): increased frequency of third and fourth degree adverse reactions;
• re-therapy: the severity and frequency of adverse reactions are consistent with those of the initial therapy.

Side effects of Acellbia registered in the post-registration period in the treatment of non-Hodgkin's lymphoma and chronic lymphocytic leukemia:

• cardiovascular system: severe heart failure, myocardial infarction (more often in patients with a history of cardiovascular pathologies and / or during cytotoxic chemotherapy); very rarely - vasculitis (often cutaneous leukocytoclastic);
• circulatory and lymphatic systems: reversible acute thrombocytopenia associated with infusion reactions; rarely - neutropenia (occurring after the last administration of rituximab after 4 weeks), a transient increase in the level of immunoglobulin with Waldenstrom's macroglobulinemia;
• respiratory organs: pulmonary infiltrates, respiratory failure, interstitial lung disease with a risk of fatal outcome;
• dermatological reactions: rarely - toxic epidermal necrolysis, severe bullous reactions, Stevens-Johnson syndrome with a risk of death;
• nervous system: rarely - neuropathy of the cranial nerves (without or in combination with peripheral neuropathy) in different periods of treatment and for several months after the completion of the course, cases of reversible encephalopathy with damage to the posterior parts of the brain (headache, visual impairment, convulsions, mental disorders with or without increased blood pressure);
• infections: reactivation of viral hepatitis B (more often when combined with cytotoxic chemotherapy), other severe viral infections (primary infection, exacerbation or reactivation of the virus), including those caused by the hepatitis C virus, cytomegalovirus, Herpes simplex, Varicella zoster, JC poliomavirus (PML) with the risk of death;
• gastrointestinal tract: in non-Hodgkin's lymphoma - perforation of the stomach and / or intestines with a risk of death (when combined with chemotherapy);
• from the body as a whole, reactions at the injection site: rarely - serum sickness.

Overdose

Cases of overdose of the drug Acellbia were not observed. The effects of rituximab with a single dose of more than 1000 mg have not been studied. There are known episodes when a maximum dose of 5000 mg was prescribed to patients with chronic lymphocytic leukemia, but additional data on the safety of the drug were not obtained. It has been established that when the pool of B-lymphocytes is depleted, the risk of infectious complications increases; therefore, it is recommended to cancel Acellbia or reduce the infusion rate, and, if necessary, conduct a detailed general blood test.

special instructions

The use of Acellbia is indicated only in a hospital equipped with equipment and means for carrying out resuscitation measures (including adrenaline, antihistamines, GCS), under the close supervision of an oncologist or hematologist.

In most cases, after 0.5–2 hours from the beginning of the first infusion, patients develop a fever with trembling and chills. Its development may be due to the release of mediators, including cytokines. Severe forms of infusion reactions are similar in symptomatology to cytokine release syndrome or hypersensitivity reactions, which include a decrease in blood pressure, nausea, vomiting, itching, weakness, pulmonary disorders, headache, urticaria, angioedema, pain in the foci of the disease, tongue irritation, edema pharynx, rhinitis, hot flashes, sometimes - signs of rapid tumor lysis syndrome. To relieve the symptoms of an infusion reaction, it is necessary to interrupt the administration of rituximab and carry out drug therapy using intravenous administration of 0.9% sodium chloride solution, acetaminophen, diphenhydramine, GCS,bronchodilators and other essential medicines. Usually, after a complete recovery of the state, the infusion is resumed at a rate reduced by 50%, often the course of treatment can be completely completed, since the re-development of severe infusion reactions is rare.

With the development of side effects from the lungs - hypoxia, pulmonary infiltrates, acute respiratory failure - patients must be carefully monitored until the symptoms disappear completely. Acute respiratory failure often occurs within the first 1–2 hours after the start of the first infusion. Due to the risk of interstitial infiltrates or pulmonary edema in the lungs, if severe reactions develop from the lungs, the infusion should be stopped immediately and intensive symptomatic therapy should be started.

Patients at risk (with a high tumor load or the number of circulating malignant cells exceeding 25,000 per μl) should be under close medical supervision. They need to ensure that regular laboratory tests are carried out for the timely determination of the symptoms of rapid tumor lysis, and in the case of a diagnosis of this pathology, start appropriate therapy. Tumor lysis syndrome can develop after the first infusion of rituximab, sometimes after complete relief of symptoms, therapy can be continued in combination with appropriate prevention of rapid tumor lysis syndrome.

If the tumor load is high or the number of circulating malignant cells exceeds 25,000 per μl, the dose of the first infusion should be divided into two days during the first and all subsequent cycles, or administered at a slower rate.

Due to the risk of hypotension, antihypertensive drugs should be discontinued at least 12 hours before the infusion.

The use of Acellbia should be accompanied by regular detailed analysis of peripheral blood.

Before prescribing the drug, all patients should be screened for hepatitis B, with an active form of the disease, use is contraindicated. If you have a positive hepatitis B serological marker, you should consult a hepatologist.

If the development of toxic epidermal necrolysis and Stevens-Johnson syndrome is detected, Acellbia should be canceled. The question of the use of rituximab in this case should be decided taking into account the balance of benefits and risks of therapy for each patient individually.

Women of childbearing age need to use reliable contraceptive methods for the entire treatment period and the 12 months following.

Vaccination with live viral vaccines is not recommended. Inactivated vaccines can be used, but response rates may be reduced.

Influence on the ability to drive vehicles and complex mechanisms

The influence of Acellbia on the patient's ability to drive vehicles and mechanisms has not been established.

Application during pregnancy and lactation

Immunoglobulins G can cross the placental barrier. B-cell levels have not been studied in newborns whose mothers received Acellbia during pregnancy. Some infants had lymphocytopenia and temporary depletion of the B-cell pool. The safety and effectiveness of rituximab in pregnant women has not been established. In this regard, the drug is contraindicated during pregnancy. Women of childbearing age during the period of therapy and for 12 months after its termination should use reliable methods of contraception.

It is unknown whether rituximab is excreted in breast milk. However, it has been established that immunoglobulins G circulating in the woman's blood pass into milk. For this reason, the use of Acellbia during lactation is contraindicated.

Pediatric use

This anticancer drug is not used in children and adolescents (up to 18 years) due to the lack of data on the efficacy and safety of rituximab in patients of this age group.

Use in the elderly

No dose adjustment of Acellbia is required in elderly patients.

Drug interactions

The simultaneous use of rituximab, cyclophosphamide and fludarabine in chronic lymphocytic leukemia does not change the pharmacokinetic parameters.

The combination of Acellbia for the purpose of diagnosis or treatment with other monoclonal antibodies in patients who have antibodies against mouse proteins or anti-chimeric antibodies increases the risk of developing allergic reactions.

For the introduction of Acellbia solution, it is recommended to use infusion systems or bags made of polyvinyl chloride and polyethylene.

Analogs

The analogues of Acellbia are Avastin, Actemra, Bevacizumab, Vectibix, Herceptin, Campas, Mabtera, Removab, Simzia, Simponi, Tizabri, Erbitux.

Terms and conditions of storage

Keep out of the reach of children.

Store in a dark place at a temperature of 2-8 ° C, do not freeze.

The shelf life is 30 months.

Terms of dispensing from pharmacies

Dispensed by prescription.

Reviews about Acellbia

Taking into account the specificity of the use of the drug, patients are reluctant to talk about their well-being, therefore, there are no reviews about Acellbia on specialized medical forums and websites, which would allow assessing the effectiveness and degree of safety of this domestic anticancer agent.

Price for Acellbia in pharmacies

Approximate prices for Acellbia: 2 bottles of 10 ml - 16,800-19,000 rubles, 1 bottle of 30 ml - 28,300 rubles, 1 bottle of 50 ml - 42,000–46,120 rubles.

Acellbia: prices in online pharmacies

Drug name Price Pharmacy

Acellbia 10 mg / ml concentrate for preparation of solution for infusion 10 ml 2 pcs. RUB 10,000 Buy

Acellbia 10 mg / ml concentrate for preparation of solution for infusion 50 ml 1 pc. RUB 30,000 Buy

Anna Kozlova Medical journalist About the author

Education: Rostov State Medical University, 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!