What is the active ingredient in BENDAMUSTINE ACCORD 25MG/ML Concentrate for solution for infusion?

Bendamustini hydrochloridum (Bendamustini hydrochloridum)

Is BENDAMUSTINE ACCORD 25MG/ML Concentrate for solution for infusion OTC or prescription only?

BENDAMUSTINE ACCORD 25MG/ML Concentrate for solution for infusion requires a doctor's prescription.

What are the side effects of BENDAMUSTINE ACCORD 25MG/ML Concentrate for solution for infusion?

The most common adverse reactions associated with the use of bendamustine hydrochloride are haematological adverse reactions (leucopenia, thrombocytopenia), dermatological toxicity (allergic reactions), constitutional symptoms (pyrexia) and gastrointestinal symptoms (nausea, vomiting). The table below presents data obtained with bendamustine hydrochloride. MedDRA System Organ Class Very common ≥1/10 Common ≥1/100 to <1/10 Uncommon ≥1/1,000 to <1/100 Rare ≥1/10,000 to <1/1,000 Very rare <1/10,000

Does BENDAMUSTINE ACCORD 25MG/ML Concentrate for solution for infusion interact with other medications?

No in vivo interaction studies have been conducted. When bendamustine is administered in combination with myelosuppressive agents, the effect of bendamustine and/or concomitant medicinal products on the bone marrow may be potentiated. Any treatment that reduces the patient's performance status or impairs bone marrow function may increase the toxicity of bendamustine. The combination of bendamustine with ciclosporin or tacrolimus may result in excessive immunosuppression with a

BENDAMUSTINE ACCORD 25MG/ML Concentrate for solution for infusion

This information is for educational purposes only. It is not intended as medical advice. Always consult a qualified healthcare professional.

Pharmacotherapeutic group: antineoplastic agents, alkylating agents.‍‍‍‍‍‍‍ ATC code: L01AA09. Bendamustine hydrochloride is an alkylating antineoplastic agent with unique activity. The cytostatic and cytocidal effect of bendamustine hydrochloride is essentially based on cross-linking of single-strand and double-strand DNA through alkylation, resulting in disruption of DNA template functions and disruption of DNA synthesis and repair. The antineoplastic effect of bendamustine hydrochloride has been demonstrated in various human tumour cell lines (breast carcinoma, non-small cell and small cell lung carcinoma, ovarian carcinoma and various types of leukaemia) in several in vitro studies and in tumours of murine, rat and human origin (melanoma, breast carcinoma, sarcoma, lymphoma, leukaemia and small cell lung carcinoma) in various experimental in vivo tumour models. In human tumour cell lines, bendamustine hydrochloride exhibited an activity profile distinct from that of other alkylating agents. Bendamustine hydrochloride showed no cross-resistance, or only very low cross-resistance, in human tumour cell lines with various mechanisms of resistance; this property is at least partly due to the relatively strong binding to DNA. Furthermore, clinical studies have shown that there is no complete cross-resistance of bendamustine with anthracyclines, alkylating agents or rituximab. However, the number of patients evaluated is low. Chronic lymphocytic leukaemia The indication for use in the treatment of chronic lymphocytic leukaemia is supported by one open-label study comparing bendamustine with chlorambucil. This prospective, multicentre, randomised study enrolled 319 previously untreated patients with chronic lymphocytic leukaemia Binet stage B or C requiring treatment. First-line treatment with bendamustine hydrochloride at a dose of 100 mg/m2 i.v. on days 1 and 2 (BEN) was compared with chlorambucil at a dose of 0.8 mg/kg on days 1 and 15 (CLB) for 6 cycles in both arms. Patients received allopurinol to prevent tumour lysis syndrome. Patients treated with the BEN regimen showed significantly longer median progression-free survival than patients treated with the CLB regimen (21.5 versus 8.3 months, p < 0.0001, at last follow-up). The difference in overall survival was not statistically significant (median not reached). Median duration of remission was 19 months with BEN treatment and 6 months with CLB treatment (p < 0.0001). Safety evaluation in both treatment arms revealed no unexpected type or frequency of adverse events. The BEN dose was reduced in 34% of patients. In 3.9% of patients, BEN treatment was discontinued due to allergic reactions. Indolent non-Hodgkin lymphomas The indications for indolent non-Hodgkin lymphomas are based on two uncontrolled phase II studies. In the pivotal prospective, multicentre, open-label study, 100 patients with indolent B-cell non-Hodgkin lymphomas refractory to rituximab administered as monotherapy or in combination therapy were treated with bendamustine hydrochloride as monotherapy. Patients had received a median of 3 prior chemotherapy or biological therapy treatment cycles. The median number of prior rituximab-containing therapies was 2. Patients had not responded to treatment or had progressed within 6 months of rituximab treatment. The BEN dose was 120 mg/m2 i.v. on days 1 and 2 and was planned for at least 6 cycles. Duration of treatment depended on response (6 cycles planned). The overall response rate was 75%, which included 17% complete responses (CR and CRu) and 58% partial responses, as assessed by an independent review committee. The median duration of remission was 40 weeks. BEN administered according to the above dosage and schedule is generally well tolerated. This indication is also supported by another prospective, multicentre, open-label study involving 77 patients. The patient population was more heterogeneous and included: indolent or transformed B-cell non-Hodgkin lymphomas refractory to rituximab as monotherapy or in combination therapy. Patients had not responded or had progressed within 6 months or had experienced an adverse reaction to prior rituximab treatment. Patients had received a median of 3 prior chemotherapy or biological therapy treatment cycles. The median number of prior rituximab-containing therapies was 2. The overall response rate was 76% with a median duration of response of 5 months (29 [95% CI 22.1; 43.1] weeks). Multiple myeloma One hundred and thirty-one patients with advanced multiple myeloma (Durie-Salmon stage II with progression or stage III) were enrolled in a prospective, multicentre, randomised, open-label study. First-line treatment with bendamustine hydrochloride in combination with prednisone (BP) was compared with melphalan and prednisone (MP). Tolerability in both treatment arms was consistent with the known safety profile of the respective medicinal products, with significantly greater dose reduction in the BP arm. The dose consisted of bendamustine hydrochloride 150 mg/m2 i.v. on days 1 and 2 and prednisone, or melphalan 15 mg/m2 i.v. on day 1 and prednisone. Duration of treatment depended on response and was on average 6.8 cycles in the BP group and 8.7 cycles in the MP group. Patients treated with the BP regimen showed longer median progression-free survival than patients treated with the MP regimen (15 [95% CI 12-21] versus 12 [95% CI 10-14] months) (p=0.0566). Median time to treatment failure was 14 months with BP and 9 months with MP. Duration of remission was 18 months with BP and 12 months with MP. The difference in overall survival was not statistically significant (35 months for the BP arm versus 33 months for the MP arm). Tolerability in both treatment arms was consistent with the known safety profile of the respective medicinal products, with significantly greater dose reduction in the BP arm.

⚠️ Warnings

Myelosuppression Patients treated with bendamustine hydrochloride may experience myelosuppression.‍‍‍‍‍‍‍ In case of treatment-induced myelosuppression, leukocyte counts, platelet counts, haemoglobin levels and neutrophil counts must be monitored at least once weekly. Initiation of the next treatment cycle is recommended only after the following parameters have been reached: leukocyte and/or platelet values > 4,000/µl and > 100,000/µl respectively. Infections Serious and fatal infections have occurred with bendamustine hydrochloride, including bacterial infections (sepsis, pneumonia) and opportunistic infections such as Pneumocystis jirovecii pneumonia (PJP), varicella zoster virus (VZV) and cytomegalovirus (CMV). Cases of progressive multifocal leukoencephalopathy (PML), including fatal cases, have been reported following use of bendamustine, particularly in combination with rituximab or obinutuzumab. Treatment with bendamustine hydrochloride may cause prolonged lymphocytopenia (< 600/μl) and low CD4-positive T-cell counts (helper T-cells) (< 200/μl), which may persist for at least 7–9 months after the end of treatment. Lymphocytopenia and CD4-positive T-cell depletion are more pronounced when bendamustine is combined with rituximab. Patients with lymphopenia and low CD4-positive T-cell counts are more susceptible to (opportunistic) infections following treatment with bendamustine hydrochloride. In case of low CD4-positive T-cell counts (< 200/μl), prophylaxis for Pneumocystis jirovecii pneumonia (PJP) should be considered. All patients should be monitored for respiratory signs and symptoms during treatment. Patients should be advised to report new signs of infection promptly, including fever or respiratory symptoms. In the event of signs of (opportunistic) infections, discontinuation of bendamustine hydrochloride should be considered. In patients with new or worsening neurological, cognitive or behavioural signs or symptoms, PML should be considered in the differential diagnosis. If PML is suspected, appropriate diagnostic evaluations should be performed and treatment should be withheld until PML has been excluded. Hepatitis B reactivation Hepatitis B reactivation has occurred in patients who are chronic carriers of the hepatitis B virus following administration of bendamustine hydrochloride. Some cases resulted in acute hepatic failure or death. Patients should be tested for HBV infection before initiating treatment with bendamustine hydrochloride. Patients with positive hepatitis B serology (including those with active disease) should consult hepatologists and specialists in hepatitis B treatment before initiating therapy; the same applies to patients who test positive for HBV infection during treatment. HBV carriers who require treatment with bendamustine hydrochloride should be closely monitored for signs and symptoms of active HBV infection throughout treatment and for several months after discontinuation (see section 4.8). Skin reactions Numerous skin reactions have been reported, including rash, severe skin reactions and bullous exanthema. Cases of Stevens-Johnson syndrome (SJS), toxic epidermal necrolysis (TEN) and drug reaction with eosinophilia and systemic symptoms (DRESS) have been reported with bendamustine hydrochloride, some of them fatal. Patients should be advised by their prescribers about the signs and symptoms of these reactions and should be informed to seek immediate medical attention if these symptoms occur. Some of these cases occurred when bendamustine hydrochloride was administered in combination with other antineoplastic agents; therefore, the precise relationship is uncertain. If skin reactions occur, they may progress and increase in severity with continued treatment. If skin reactions progress, bendamustine should be interrupted or discontinued. In case of severe skin reactions suspected to be related to bendamustine hydrochloride, treatment should be discontinued. Cardiac disorders During treatment with bendamustine hydrochloride, serum potassium levels must be carefully monitored in patients with cardiac disorders, and potassium supplements must be administered if K+ < 3.5 mEq/l; ECG monitoring must also be performed. Fatal cases of myocardial infarction and cardiac failure have been reported during treatment with bendamustine hydrochloride. Patients with cardiac disease, including a history thereof, should be monitored closely. Nausea, vomiting Antiemetics may be administered for the symptomatic treatment of nausea and vomiting. Tumour lysis syndrome Tumour lysis syndrome (TLS) associated with bendamustine treatment has been reported in patients in clinical trials. It usually manifests within 48 hours of the first dose of bendamustine and, if untreated, may lead to acute renal failure and death. Preventive measures should be considered before initiating treatment, such as ensuring adequate hydration, close monitoring of blood chemistry parameters, particularly potassium and uric acid levels, and the use of hypouricaemic agents (allopurinol and rasburicase). Several cases of Stevens-Johnson syndrome and toxic epidermal necrolysis have been reported with concomitant administration of bendamustine and allopurinol. Anaphylaxis In clinical trials, infusion reactions to bendamustine hydrochloride occurred frequently. Symptoms are usually mild and include fever, chills, pruritus and rash. In rare cases, severe anaphylactic and anaphylactoid reactions have occurred. After the first cycle of treatment, patients should be asked whether they have experienced symptoms suggestive of an infusion reaction. In patients with a history of infusion reactions, preventive measures against severe reactions, including antihistamines, antipyretics and corticosteroids, should be considered during subsequent cycles. Patients who experienced grade 3 or higher allergic-type reactions were generally not re-treated. Contraception Bendamustine hydrochloride is teratogenic and mutagenic. Women should not become pregnant during treatment. Men should be advised about sperm conservation before starting treatment with bendamustine hydrochloride due to the possibility of irreversible infertility. Extravasation Extravasation must be stopped immediately. The needle should be removed after brief aspiration. The affected tissue area should then be cooled. The arm should be elevated. Additional treatment, such as administration of corticosteroids, has no clear benefit. Non-melanoma skin cancer In clinical trials, an increased risk of non-melanoma skin cancer (basal cell carcinoma and squamous cell carcinoma) was observed in patients receiving bendamustine-containing treatment. Regular skin examinations are recommended for all patients, particularly those with risk factors for skin cancer. Dilution Bendamustine Accord requires appropriate dilution before use. The concentration of bendamustine in Bendamustine Accord 25 mg/ml concentrate for solution for infusion differs from other bendamustine-containing products (for further dilution instructions, see section 6.6).

BENDAMUSTINE ACCORD 25MG/ML Concentrate for solution for infusion

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