bendamustine hydrochloride

bendamustine hydrochloride

Treanda

Pharmacologic class: Alkylating agent

Therapeutic class: Antineoplastic

Pregnancy risk category D

Action

Unclear. Dissociates into electrophilic alkyl groups, which form covalent bonds with electron-rich nucleophilic moieties; bifunctional covalent linkage may cause cell death via several pathways. Acts against both quiescent and dividing cells.

Availability

Lyophilized powder for injection: 100 mg in 20-ml single-use vials (with mannitol)

Indications and dosages

Chronic lymphocytic leukemia

Adults: 100 mg/m2 by I.V. infusion over 30 minutes on days 1 and 2 of 28-day cycle for up to six cycles

Dosage adjustment

• Grade 4 hematologic toxicity or clinically significant nonhemologic toxicity at above grade 2

Off-label uses

• Non-Hodgkin's lymphoma

Contraindications

• Hypersensitivity to drug or mannitol

Precautions

Use cautiously in:

• mild or moderate renal impairment (not recommended in creatinine clearance less than 40 ml/minute)

• mild hepatic impairment (not recommended in moderate or severe hepatic impairment)

• myelosuppression

• concurrent use of CYP1A2 inhibitors or inducers

• pregnant or breastfeeding patients

• children (safety and efficacy not established).

Administration

• Give drug by I.V. infusion only.

• Reconstitute with 20 ml sterile water for injection. Wait until powder dissolves completely (approximately 5 minutes).

• Immediately transfer (within 30 minutes of reconstitution) to 500-ml infusion bag of normal saline injection. After transferring, thoroughly mix infusion bag contents. Admixture should be clear and colorless to slightly yellow.

Stay alert for infusion reactions. Signs and symptoms include fever, chills, pruritus, and rash. Rarely, severe anaphylactic and anaphylactoid reactions have occurred. Monitor patient and discontinue drug if severe reaction arises. Consider measures to prevent severe reactions, including antihistamines, antipyretics, and corticosteroids in subsequent cycles if patient had previous infusion reaction.

• Check I.V. site frequently to avoid extravasation.

Adverse reactions

CNS: asthenia, fatigue, malaise, weakness, somnolence, headache

CV: worsening hypertension

EENT: nasopharyngitis

GI: nausea, vomiting, diarrhea, constipation, dry mouth, mucosal inflammation, stomatitis

Hematologic: myelosuppression (anemia, leukopenia, lymphopenia, neutropenia, thrombocytopenia)

Metabolic: hyperuricemia

Respiratory: cough, pneumonia

Skin: rash, pruritus, toxic skin reactions, bullous exanthema, Stevens-Johnson syndrome, toxic epidermal necrolysis

Other: fever, chills, infection, herpes simplex, weight loss, other malignancies, tumor lysis syndrome, sepsis, infusion reactions and anaphylaxis, hypersensitivity reaction

Interactions

Drug-drug. Allopurinol: possible increased risk of skin reactions

CYP1A2 inducers (such as omeprazole): potentially decreased bendamustine blood level and increased active metabolite levels

CYP1A2 inhibitors (such as ciprofloxacin, fluvoxamine): potentially increased bendamustine blood level and decreased active metabolite levels

Drug-diagnostic tests. ALT, AST, bilirubin, uric acid: increased levels Creatinine: altered level

Hemoglobin, lymphocytes, neutrophils, platelets, white blood cells: decreased levels

Potassium, uric acid: increased levels

Drug-behaviors. Smoking: potentially decreased bendamustine blood level and increased active metabolite levels

Patient monitoring

• Closely monitor complete blood count with differential and renal and hepatic function test results.

Monitor for skin reactions, including rash, toxic reactions, and bullous exanthema. Such reactions may be progressive and worsen with further treatment. In severe or progressive skin reaction, withhold or discontinue drug.

Watch for tumor lysis syndrome, especially during first treatment cycle. Signs and symptoms include irregular heartbeat, shortness of breath, high potassium level, high uric acid level, and impaired mental ability. Without intervention, acute renal failure and death may occur. Take preventive measures, as ordered, including maintaining adequate volume status, close monitoring of blood chemistry, and allopurinol administration during first 2 weeks of therapy in high-risk patients. However, be aware that concomitant use of allopurinol may increase risk of severe skin toxicity.

Patient teaching

• Instruct patient to report unusual bleeding or bruising, fever, chills, and lip or mouth sores.

• Inform patient that drug may increase risk of infection. Advise patient to wash hands frequently, wear mask in public places, and avoid people with infections.

• Advise female that drug may harm fetus; caution her to avoid becoming pregnant. If patient is pregnant during therapy or becomes pregnant, inform her of risk to fetus.

• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs, tests, and behaviors mentioned above.

References in periodicals archive ?
Eagle Pharmaceuticals announced that the FDA has granted seven years of orphan drug exclusivity, or ODE, in the U.S., for Bendeka, a liquid, low-volume and short-time 10-minute infusion formulation of bendamustine hydrochloride. As a result, and consistent with the order issued by the U.S.
Eagle Pharmaceuticals Inc (NASDAQ:EGRX) has been granted an additional patent for BENDEKA (bendamustine hydrochloride) injection, the pharmaceutical company announced on Tuesday.
announced today that the anticancer agent TREAKISYM for Injection 100 mg (generic name: bendamustine hydrochloride, "TREAKISYM") has been approved in Japan for an additional indication of chronic lymphocytic leukemia.
Bendamustine hydrochloride is an alkylating agent that has a unique, multifaceted mechanism of action.
Titled "Bendamustine: A Novel Cytotoxic Agent for Hematologic Malignancies," it notes that bendamustine hydrochloride has a chemical structure containing alkylating nitrogen mustard, contributing to its cytotoxic properties.
The company's proprietary products in the United States include: AMRIX (cyclobenzaprine hydrochloride extended-release capsules), TREANDA (bendamustine hydrochloride) for Injection, FENTORA (fentanyl buccal tablet) (C-II), PROVIGIL (modafinil) Tablets (C-IV), TRISENOX (arsenic trioxide) injection, GABITRIL (tiagabine hydrochloride), NUVIGIL (armodafinil) Tablets (C-IV) and ACTIQ (oral transmucosal fentanyl citrate) (C-II).
M2 PHARMA-May 21, 2018-FDA Grants Eagle Pharmaceuticals Approval for Bendamustine Hydrochloride Ready-to-Dilute Solution in a 500ml Admixture
Teva Pharmaceutical Industries (NYSE:TEVA)(TASE:TEVA) and Eagle Pharmaceuticals (EGRX) on Wednesday jointly announced that the Centers for Medicare & Medicaid Services (CMS) has adopted the unique, product-specific billing code, or J-code (J9034), for BENDEKA (bendamustine hydrochloride) Injection.
today launched the anticancer agent TREAKISYM(R) Injection 100 mg (bendamustine hydrochloride) in Japan as a treatment for low-grade B-cell non-Hodgkin's lymphoma and mantle cell lymphoma.
M2 PHARMA-November 3, 2016-Teva Pharmaceutical Industries announces CMC grant of Unique J-Code for BENDEKA (Bendamustine Hydrochloride) Injection
Pharmaceutical company Eagle Pharmaceuticals (NasdaqGM:EGRX) reported on Tuesday the receipt of the sixth patent from the US Patent and Trademark Office (USPTO) for its liquid bendamustine hydrochloride (HCl) formulations.
SymBio Pharmaceuticals Limited acquired the exclusive rights to develop and market bendamustine hydrochloride in Japan, China, South Korea, Taiwan and Singapore from Astellas Deutschland GmbH (Headquarters: Munich, Germany, formerly Astellas Pharma GmbH).