Indication:
TREANDA® (bendamustine hydrochloride) for Injection, for intravenous
infusion
Initial U.S. Approval: 2008
RECENT MAJOR CHANGES
Indications and Usage, Non-Hodgkins Lymphoma (NHL) (1.2) 10/2008
Dosage and Administration, Dosing Instructions for NHL (2.2) 10/2008
Dosage and Administration, Reconstitution/Preparation for Intravenous
Administration (2.4) 10/2008
Dosage and Administration, Admixture Stability (2.5) 10/2008
Warnings and Precautions, Myelosuppression (5.1) 10/2008
Warnings and Precautions, Skin Reactions (5.5) 10/2008
Warnings and Precautions, Other Malignancies (5.6) 10/2008
Bendamustine Hydrochloride lyophilised Injection 25mg (Additional Srength)
Indication-
Treatment of patients with chronic lymphocytic leukemia
Approved by FDA on 19-09-2014 (Ref- FDA approved List- 2014)
New drugs approved For Marketing by Drug Controller General of India(DCGI )
during the period January 1988 to November 2014
(Ref- IDMA Annual Publication 2015)
Name of Drug Indication Date of Approval
1.Bendamustine hcl lypphilised injection 100mg vial 16-05-2009
For the treatment of patients with chronic lymphocytic leukemia
2. Bendamustine hcl lyophilised injection 25mg 19-09-2014
Addl.strgth
Treatment of patients with chronic lymphocytic leukemia
Chronic lymhocytic leukemia -CLL
Non - Hodgkin lymphoma - NHL
Adverse Reaction:
Most frequent adverse reactions were predominently
hypersensitivity 2% and pyrexia 1%
CNS -
Asthenia 7% Chills 5% Fatigue 8%
Dermatologic -
Pruritus 4% Rash 6%
GI -
Diarrhea 8% Nausea 18% Vomiting 14%
Metabolic /Nutrional -
Hyperurenia 5% weight reduced 5%
Respiratory -
Cough 3% Nasopharyngitis 5%
Miscellaneous -
Herpes simplex 2% Hypersensitivity 4% Infection 5% Pyrexia 21%
Contra-Indications:
Known hypersensitivity
Special Precatuions/ warnings-
Mylosuppressants - patients treated with bendamustine are likely to experience mylosuppression
Infections- infections including pneumonia ans sepsis has been reported during clinical trials. Advice patients to consult doctor in case of signs of infection
Infusion reactions and anaphylaxis - infusion reactions to bendamustine have occurred in clincal trials. Consider disconitinuation in patients with infusion reactions
Skin reactions- a number of skin reactions have been reported in clinical trials.
Renal function impairment - bendamustine with caution in patients with mild or moderate renal function impairment
Pregnancy - if this drug is taken during pregnancy or if the patient becomes pregnant while
taking the drug, appraise the patient the potential hazard to the fetus.
Lactation- decide whether to discontinue nursing or the drug depending upon imporatance
of the drug to mother.
Children- safety and efficacy of the drug in children have not been established.
Dosages/ Overdosage Etc:
Indication-
Chronic lymhocytic leukemia -CLL
Non - Hodgkin lymphoma - NHL
Dosage-
Usual dosage- 100mg.m2 administered intravenously IV over 30 minutes on day 1 and 2
of a 28 day cycle upto 6 cycles.
Store at upto 25 C (77F )
Patient Information:
1. Inform patients of the possibility of a mild or serious allergic reactions and advuce them
to immediately report rash, facial swelling, or difficulty in breathing during or soon after infusion.
2. Inform patients that bendamustine may cause a decrease in WBC, platelets, and red blood cells. This will need frequent monitoring of these parameters.
3. Inform patients to report shortness of breath, significant fatigue, fever or other signs of infection.
4. Bandamustine may cause fetal harm. Advice women not to be become pregnant throughout treatment and for 3 months after Bendamustine therapy is stopped. Advice patients to use reliable contraceptives for the same period.
5. Advice patients to avoid breast feeding while receiving Bendamustine.
6. Advice patients that Bendamustine may cause tiredness and to avoid driving or operate any dangerous tools or machinery if they experience this adverse reaction.
7. Advice patients that Bendamustine may cause nausea or vomiting. Instruct patients to report the same to the doctor if the adverse reaction is severe.
8. Advice patients that Bendamustine may cause diarrhea. If the adverse reaction turns serious they should report to the doctor.
9. Advice patients that a mild rash or itching occur during treatment with Bendamustine. Advice them to report immediately to their doctor.
Pharmacology/ Pharmacokinetics:
CLINICAL PHARMACOLOGY
1. Mechanism of Action
Bendamustine is a bifunctional mechlorethamine derivative containing a purine-like
benzimidazole ring. Mechlorethamine and its derivatives form electrophilic alkyl groups.
These groups form covalent bonds with electron-rich nucleophilic moieties,
resulting in interstrand DNA crosslinks.
The bifunctional covalent linkage can lead to cell death via several pathways.
Bendamustine is active against both quiescent and dividing cells.
The exact mechanism of action of bendamustine remains unknown.
2. Pharmacokinetics
Absorption
Following a single IV dose of bendamustine hydrochloride Cmax typically occurred
at the end of infusion. The dose proportionality of bendamustine has not been studied.
Distribution
In vitro, the binding of bendamustine to human serum plasma proteins ranged from
94-96% and was concentration independent from 1-50 ìg/mL.
In humans, the mean steady state volume of distribution (Vss) was approximately 25 L.
Pregnancy and lactation:
USE IN SPECIFIC POPULATIONS
1. Pregnancy
Pregnancy Category D
TREANDA can cause fetal harm when administered to a pregnant woman.
If this drug is used during pregnancy, or if the patient becomes pregnant while
taking this drug, the patient should be apprised of the potential hazard to the fetus.
2. Nursing Mothers
It is not known whether this drug is excreted in human milk. Because many drugs
are excreted in human milk and because of the potential for serious adverse
reactions in nursing infants and tumorigenicity shown for bendamustine in
animal studies, a decision should be made whether to discontinue nursing
or to discontinue the drug, taking into account the importance of the drug to the mother.
3. Pediatric Use
The safety and effectiveness of TREANDA in pediatric patients have not been established.
4. Geriatric Use
In CLL and NHL studies, there were no clinically significant differences in the adverse
reaction profile between geriatric (. 65 years of age) and younger patients.
Manufacturer Details