Luhan Pharmachem Co., Ltd.

Luhan pharmachem Co., Ltd. supplies Bendamustine HCl bulk active pharmaceutical ingredient (API) to the pharmaceutical industry. Our Bendamustine HCl is manufactured by cGMP compliant facility. Welcome to contact us for further details including current DMF status for the product and up to date regulatory status of the manufacturing facility. We look forward to assisting you with your research and development projects.

What is Bendamustine HCl?

Bendamustine HCl is a rationally designed purine analog and alkylator hybrid. It damages the DNA in cancer cells, sick which leads to the normal path of cell death (apoptosis). It also stops cancer cells from dividing to create new cancer cells.

Bendamustine HCl is specifically indicated for: 1) the treatment of chronic lymphocytic leukemia where efficacy relative to first line therapies other than chlorambucil has not been established, and 2) indolent B-cell non-Hodgkins lymphoma that has progressed during or within six months of treatment with rituximab or a rituximab-containing regimen. Its empirical molecular formula is C16H21Cl2N3O2•HCl, and the molecular weight is 394.7.

Bendamustine HCl Drug Interactions

No formal clinical assessments of pharmacokinetic drug-drug interactions between Bendamustine HCl and other drugs have been conducted.

Bendamustine’s active metabolites, gamma-hydroxy bendamustine (M3) and N-desmethyl-bendamustine (M4), are formed via cytochrome P450 CYP1A2. Inhibitors of CYP1A2 (e.g., fluvoxamine, ciprofloxacin) have potential to increase plasma concentrations of bendamustine and decrease plasma concentrations of active metabolites. Inducers of CYP1A2 (e.g., omeprazole, smoking) have potential to decrease plasma concentrations of bendamustine and increase plasma concentrations of its active metabolites. Caution should be used, or alternative treatments considered if concomitant treatment with CYP1A2 inhibitors or inducers is needed.

The role of active transport systems in bendamustine distribution has not been fully evaluated. In vitro data suggest that P-glycoprotein, breast cancer resistance protein (BCRP), and/or other efflux transporters may have a role in bendamustine transport.

Based on in vitro data, bendamustine is not likely to inhibit metabolism via human CYP isoenzymes CYP1A2, 2C9/10, 2D6, 2E1, or 3A4/5, or to induce metabolism of substrates of cytochrome P450 enzymes.

Precautions Before Using Bendamustine HCl

Myelosuppression

Patients treated with bendamustine HCl are likely to experience myelosuppression. In the two NHL studies, 98% of patients had Grade 3-4 myelosuppression. Three patients (2%) died from myelosuppression-related adverse reactions; one each from neutropenic sepsis, diffuse alveolar hemorrhage with Grade 3 thrombocytopenia, and pneumonia from an opportunistic infection (CMV).

Infections

Infection, including pneumonia and sepsis, has been reported in patients in clinical trials and in post-marketing reports. Infection has been associated with hospitalization, septic shock and death. Patients with myelosuppression following treatment with bendamustine HCl are more susceptible to infections.

Infusion Reactions and Anaphylaxis

Infusion reactions to bendamustine HCl have occurred commonly in clinical trials. Symptoms include fever, chills, pruritus and rash. In rare instances severe anaphylactic and anaphylactoid reactions have occurred, particularly in the second and subsequent cycles of therapy.

Tumor Lysis Syndrome

Tumor lysis syndrome associated with bendamustine HCl treatment has been reported in patients in clinical trials and in post-marketing reports. The onset tends to be within the first treatment cycle of bendamustine HCl and, without intervention, may lead to acute renal failure and death. Preventive measures include maintaining adequate volume status, and close monitoring of blood chemistry, particularly potassium and uric acid levels.

Skin Reactions

A number of skin reactions have been reported in clinical trials and post-marketing safety reports. These events have included rash, toxic skin reactions and bullous exanthema. Some events occurred when bendamustine HCl was given in combination with other anticancer agents, so the precise relationship to bendamustine HCl is uncertain.

Where skin reactions occur, they may be progressive and increase in severity with further treatment. Therefore, patients with skin reactions should be monitored closely. If skin reactions are severe or progressive, bendamustine HCl should be withheld or discontinued.

Other Malignancies

There are reports of pre-malignant and malignant diseases that have developed in patients who have been treated with bendamustine HCl, including myelodysplastic syndrome, myeloproliferative disorders, acute myeloid leukemia and bronchial carcinoma. The association with bendamustine HCl therapy has not been determined.

Extravasation

There are postmarketing reports of bendamustine extravasations resulting in hospitalizations from erythema, marked swelling, and pain. Precautions should be taken to avoid extravasation, including monitoring of the intravenous infusion site for redness, swelling, pain, infection, and necrosis during and after administration of bendamustine HCl.

Use in Pregnancy

Bendamustine HCl can cause fetal harm when administered to a pregnant woman. Single intraperitoneal doses of bendamustine in mice and rats administered during organogenesis caused an increase in resorptions, skeletal and visceral malformations, and decreased fetal body weights.

Bendamustine HCl side effects

Most common non-hematologic adverse reactions for CLL (frequency ?15%) are pyrexia, nausea, and vomiting.

Most common non-hematologic adverse reactions for NHL (frequency ?15%) are nausea, fatigue, vomiting, diarrhea, pyrexia, constipation, anorexia, cough, headache, weight decreased, dyspnea, rash, and stomatitis.

Most common hematologic abnormalities for both indications (frequency ?15%) are lymphopenia, anemia, leukopenia, thrombocytopenia, and neutropenia.

Bendamustine HCl Overdose

The intravenous LD50 of bendamustine HCl is 240 mg/m2 in the mouse and rat. Toxicities included sedation, tremor, ataxia, convulsions and respiratory distress.

Across all clinical experience, the reported maximum single dose received was 280 mg/m2. Three of four patients treated at this dose showed ECG changes considered dose-limiting at 7 and 21 days post-dosing. These changes included QT prolongation (one patient), sinus tachycardia (one patient), ST and T wave deviations (two patients) and left anterior fascicular block (one patient). Cardiac enzymes and ejection fractions remained normal in all patients.

No specific antidote for bendamustine HCl overdose is known. Management of overdosage should include general supportive measures, including monitoring of hematologic parameters and ECGs.

Belimumab HCl Storage

Bendamustine HCl may be stored up to 25°C (77°F) with excursions permitted up to 30°C (86°F) (see USP Controlled Room Temperature). Retain in original package until time of use to protect from light.

Disclaimer:

Information on this page is provided for general information purposes. You should not make a clinical treatment decision based on information contained in this page without consulting other references including the package insert of the drug, textbooks and where relevant, expert opinion. We cannot be held responsible for any errors you make in administering drugs mentioned on this page, nor for use of any erroneous information contained on this page.