CANMAB-440-MG-INJECTION

Drug profile of Canmab

Canmab injection contains a targeted cancer drug known as Transtuzumab, which is pharmacologically classified as humanized monoclonal antibody produced by recombinant DNA technology.

Canmab treatment is used to reduce the rate of reactivation & mortality.

One of the epidermal growth factor receptor is known as human epidermal growth factor receptor 2 (HER2) plays vital role in breast cancer.

This factor is responsible for cell replication.

Canmab is a FDA approved product which is involved in breast cancer treatment.

CANMAB-440-MG-INJECTION

Prescribing information of Canmab

Supportive treatment for breast cancer:

Canmab should be indicated as supportive therapy for breast cancer, in which HER2 over asserting positive or negative in BC condition.

Exist in therapy regimen consisting of cyclophosphamide, doxorubicin, & paclitaxel or docetaxel.

Exist in therapy regimen with docetaxel & carboplatin

Multi modality anthracycline based treatment as a single agent.

Advanced breast cancer;

Canmab is indicated in advanced breast cancer condition, by combining with

Paclitaxel used as first line therapy.

As a lone administrator for treatment of HER2-overexpressing breast tumor in patients who have gotten no less than one chemotherapy regimens for metastatic infection.

Advanced gastric cancer:

Canmab is used to treat metastatic stage of gastric cancer, by combining with cisplatin & Capecitabine or 5-fluorouracil.

This therapy is used in patients with HER2-overexpressing metastatic gastric or gastro esophageal intersection adenocarcinoma who have not gotten earlier treatment for metastatic sickness.

Mechanism of Canmab

Canmab is a monoclonal antibody which aiming the HER2, inciting a resistant interceded reaction that causes disguise and down regulation of HER2.

HER2 pathway is essential for cell multiplication, binding of Transtuzumab to the site of HER2 causes inhibition of this activity.

This binding leads to antibody mediated and causes HER2 positive cells lysis.

Canmab is a mediator of anti-body dependent cellular cytotoxicity.

The pharmacokinetic properties of Canmab are;

Total clearance of Transtuzumab elevates by depleting the concentration due to parallel linear & non linear excretion pathways.

The Transtuzumab exposure is larger following first cycle in breast cancer patients getting 3 weekly schedules correlated to weekly schedule of Canmab.

The steady state level of Transtuzumab is higher in range.

In breast cancer;

8mg/kg + 6mg/kg for 3 times a week, Cmin value is 29.4ng/ml; Cmax value is 178ng/ml & AUC value is 1373ng.day/ml.

In metastatic GC;

8mg/kg + 6mg/kg for 3 times a week, Cmin value is 23.1ng/ml; Cmax value is 132ng/ml; & AUC value is 1109ng.day/ml.

In breast cancer;

4mg/kg + 2mg/kg qw, Cmin value is 37.7ng/ml; Cmax value is 88.3ng/ml; & AUC value is 1066ng.day/ml.

In mild renal impairment: CrCl is 60 to 90ml/min; moderate CrCl is 30 to 60ml/min.

The volume of distribution of Transtuzumab is 44ml/kg.

The metabolism of Transtuzumab is occurs intracellularly by;

Transtuzumab is metabolized into peptides & amino acids.

The excretion is a complex procedure, which is initiated by epithelial cells.

The terminal half life period of Transtuzumab is average range of 1.7 & 12 days at 10 & 500mg doses levels relatively.

The average half life is 28.5 days, the pharmacokinetics of Transtuzumab is occurs non linear, elevates doses are related to elevates the terminal mean half life & depletes the clearance.

The elimination process of Transtuzumab is involved in clearance of IgG via reticuloendothelial system.

When to take the Canmab

Canmab should be administered as intravenous infusion.

Do not administer Canmab as IV push or bolus.

Do not mix Canmab with other drugs.

Dosage regimens of Canmab

Supportive treatment for breast cancer:

In this condition total Canmab cycles is scheduled for 52 weeks.

In combination of paclitaxel, docetaxel, or docetaxel & carboplatin:

Canmab started with the dose of 4mg/kg should be administered via IV infusion over the period of 90 minutes, then resume at 2mg/kg of Canmab given as IV infusion for period of time over 30 minutes weekly during chemotherapy for first 12 weeks (paclitaxel or docetaxel) or 18 weeks (docetaxel/carboplatin).

Last week dose of Canmab is 6mg/kg should be administered as IV infusion over period of 30 to 90 minutes for every 3 weeks.

Shown as single specialist following by culmination of anthracycline based chemotherapy regimens:

The initial dose of Canmab is 8mg/kg given as IV infusion over period of 90 minutes.

The consecutive dose is 6mg/kg of Canmab should be given as IV infusion over period of 30 to 90 minutes for every 3 weeks.

Prolonged supportive treatment should not be recommended.

Advanced breast cancer:

Canmab should be administered with an initial dose of 4mg/kg, by combining with paclitaxel over a period of 90 minutes, followed by successive dose of 6mg/kg as IV infusion for 30 to 90 minutes for every 3 weeks until disease breakthrough.

Metastatic gastric cancer:

The initial dose of Canmab for this condition is 8mg/kg administered IV infusion over period of 90 minutes followed by consecutive dose of 6mg/kg as infusion over period of 30 to 90 minutes for every 3 weeks.

 Important safety points according to administration;

In case of missed cycles of Canmab therapy by one week or less, then the frequent maintenance dose (weekly schedule: 2mg/kg; 3 weekly schedule: 6mg/kg) should be given as soon as possible.

Patient does not take interval until the next planned cycle.

Successive Canmab maintenance dose should be taken in 7 days or 21 days next confer to the weekly or 3 weekly schedules.

If patient fail to take dose of Canmab by higher than one week, then resume with re-storing dose of Canmab such as weekly schedule is 4mg/kg; 3 weekly schedules is 8mg/kg should be administered over period of 90 minutes.

Infusion reactions;

In case of occurrence of infusion reactions, some precautions should be taken;

Reduce the rate of infusion in case of mild or moderate infusion reactions.

In case of dyspnea or hypotension condition, the infusion should be postponed.

For severe or life threatening infusion reactions, Canmab infusion should be discontinued.

Cardiomyopathy;

Before staring the treatment with Canmab, patients left ventricular ejection fraction should be monitored.

Interrupt the Canmab infusion for at least 4 weeks in case of any one of the following cases;

>or equal to 16% reduction of LVEF from pre-therapy values

>or equal to 10% reduction in LVEF from pre-therapy value

Administration;

Canmab contains 440mg of Transtuzumab as an active ingredient with 20ml bacteriostatic water for reconstitution.

440mg of Transtuzumab is reconstituted with 20ml of bacteriostatic water for injection containing 1.1% benzyl alcohol as a preservative.

Do not shake the vial, and then just gently swirl the vial until the contents are finely dissolved.

During reconstitution, foam should be found on vial, keep the vial aside for 5 minutes and clear solution should be formed.

Clear solution only used for dilution.

In case of any particulate matter present the solution; it should be discarding in aseptic manner.

If Canmab should be reconstituted in sterile water for injection without preservative should be used immediately and discard the unused portion.

If Canmab reconstituted in bacteriostatic water for injection, then the reconstituted solution should be stored at 2oC to 8oC for 28 days from reconstitution.

After 28 days the vial should not be used and it must be discarded.

Dilution;

Depending up on the dosing management of Canmab the diluted volume should be determined.

Canmab should be diluted in 250ml of 0.9% sodium chloride solution

Do not dilute with 5% dextrose.

Dilution should be undergone by inverting the bag and mix the solution

The infusion solution should be compatible to polyvinyl chloride or polyethylene bags.

After dilution, the infusion bag should be stored at 2oC to 8oC for not more than 24 hours befor use.

Canmab caused side effects

The most common adverse effects;

Cardiomyopathy

Infusion reactions

Embryo fetal toxicity

Pulmonary toxicity

Chemotherapy induced neutropenia

The most common side effects;

Hypertension

Dizziness

Decrease LVEF

Palpitations

Arrhythmia

Cardiac failure

Cough

Chills

Edema

Asthenia

Sudden death

Autoimmune thyroiditis

Neutropenia

Hypokalemia

Anemia

Thrombocytopenia

Febrile neutropenia

Renal failure

Influenza

Dyspnea

URI

Rhinitis

Pharyngolaryngeal pain

Sinusitis

Epistaxis

Pulmonary hypertension

Interstitial pneumonitis

Diarrhea/constipation

Nausea, vomiting

Dyspepsia

Abdominal pain

Arthralgia

Back pain

Bone pain

Headache

Paresthesia

Rash

Nail disorders

Pruritus

Pyrexia

Drug- drug interaction

If patient treated with anthracycline after conclusion of Canmab treatment may have a chance of getting cardiac dysfunction. This adverse occurs because of Transtuzumab great disaster period is depends on population PK analysis.

Avoid taking anthracycline therapy for 7 months after discontinuing the Canmab treatment.

In some exceptional condition, patient should receive anthracycline, in that condition patient’s cardiac function should be monitored carefully with regular intervals.

Food drug interaction

Foods that will interfere with the activity of Transtuzumab are;

Grape fruit

Alcohol

Beef

Butter

Cavier, cheese, milk, pork, salt

Supplements with conjugated linoleic acid

Breast cancer patients are having aberrant low iron levels.

Patients who are not having iron deficiency should not take;

Avoid to consuming spinach & dry beans, because body will absorbs heme irons more efficiently than non-heme irons from these plant sources.

Turmeric containing an active constituent like curcumin acts as iron chelator & copper chelator.

 Iron chelator means eliminating iron from the body.

Turmeric should not used in breast cancer, because it may reduce the iron content from the body.

Possible contraindications

No possible contraindicated occurs.

Infusion reactions are produced.

Hypersensitivity reactions are occurring due to patients are contraindicated to the component present in the Canmab.

Safety measures

Cardiomyopathy;

Canmab receiving patients have increased risk of exposing to cardiac disorders.

To overcome the problem by;

Monitoring cardiac functions regularly

Avoid using anthracycline drug after Canmab treatment

Provide alternative therapy management

In severe condition, therapy should be interrupt or discontinue.

Infusion reactions;

Some life threatening infusion reactions are produced during Canmab treatment.

The manifestation due to infusion reactions should be monitored frequently

Postpone the infusion of Canmab treatment and initiate the supportive measures by providing epinephrine, corticosteroids, diphenhydramine, bronchodilators, & oxygen.

In severe infusion reactions, discontinue the Canmab treatment permanently.

To overcome the problem, patient should be treated with premedication before starting the infusion.

Embryo fetal damage;

Canmab is contraindicated to pregnancy period.

Avoid becoming pregnancy during this therapy.

Use efficient contraceptives during treatment

Pulmonary toxicity;

Some severe fatal cases of pulmonary toxicity occur during Canmab treatment.

Caution should be taken during Canmab treatment.

Therapy induced neutropenia;

Higher incidence of neutropenia occurs during Canmab treatment.

Pregnancy and lactation

Canmab pregnancy category is D

Canmab should not suggest during pregnancy condition.

Breast feeding should not be recommended.

Storage and handling

Canmab vials should be stored at refrigerator temperature of 2oC to 8oC

Keep the vial away from heat & light

After reconstitution, vial should be stored at 2oC to 8oC for 28 days.

Canmab diluted bag should be stored at 2oC to 8oC for 24 hours

Missed dose

In case of missed cycles of Canmab therapy by one week or less, then the frequent maintenance dose (weekly schedule: 2mg/kg; 3 weekly schedule: 6mg/kg) should be given as soon as possible.

Patient does not take interval until the next planned cycle.

Successive Canmab maintenance dose should be taken in 7 days or 21 days next confer to the weekly or 3 weekly schedules.

If patient fail to take dose of Canmab by higher than one week, then resume with re-storing dose of Canmab such as weekly schedule is 4mg/kg; 3 weekly schedules is 8mg/kg should be administered over period of 90 minutes.

Over dosage

Maximum dose of Transtuzumab is more than 8mg/kg as a single dose.

In case of over dosage condition, patient must be;

Provide with supportive measures

Monitor the signs & symptoms due to over dosage