Brand Information

Strength	Rate	Packing Style
400mg	1152.00	10s film coated tablets

Drug Interaction:

Paracetamol, warfarin Phenytoin. ketoconazole Erythromycin, Rifampicin, Clarithromycin Itraconazole HIV antivirus Grap fruit juice St Johns Wort Dexamethasone,Carbamzepine,Phenobarbitone Statins Pimozide,Benzodiazepines Dihydropyridine, Calcium channel blockers, Cyclosporine

Indication:

GLEEVEC (imatinib mesylate) tablets for oral use

Initial U.S. Approval: 2001

RECENT MAJOR CHANGES

Indications and Usage: GIST (1.9)

Dosage and Administration: GIST (2.8)

Dose Modification Guidelines: (2.9)

Warnings and Precautions: Hepatotoxicity (5.5),

Hemorrhage (5.6), Renal Impairment (5.10),

Hypothyroidism (5.11)

Imatinab mesilate 100mg/400mg tablets and 100mg capsules

(Additional Indication)

Indication-

teatment of Paediatric patients with newly diagnosed Philadelphia

chromosome positive acute Lymphoblastic Leukaemia

(Ph+ALL) integrated with chemotherapy

Approved by FDA on 09-09-2014 (Ref- FDA approved List- 2014)

Chronic myeloid leukaemia

Approved by (DCI) Drug Controller GENERAL - India For Marketing

(Ref- IDMA Publication)

Name of Drug Indication Date of Approval

1.Imatinab Mesylate Anti-cancer 09-12-2001

2.Imitinab mesylate 05-04-2014

100mg/400mg tablets

( Addl.Indn.)

Adjuvant treatment of adult patients following resection of Gastro-intestinal

stromal tumors (GIST)

3.Imitinab mesylate 100/400mg 09-09-2014

Tablets and 100mg capsules

(Addl.Indctn.)

Treatment of pediatric patients with newly diagnosed philadelphia

chromosome positive acute lymphoblastic leukaemia (PH+ALL)

integrated chemotherapy

Adverse Reaction:

Severe non-haematological reactions,Discontinue until resolved Raised bilirubin or transaminase , with hold until levels < 1.5 IULN and < 2.5 IULN respy, then reinstate at lower dose Severe neutropenia, thrombocytopenia oe anemia reduce dose or interupt treatment GI upset, anorexia, headache, dizziness, taste disturbance Blurred vision Fluid retention Odema, investigate rapid weight gain

Contra-Indications:

Pregnancy Lactation

Special precautions- Hepatic or severe renal impairment History of cardiac disease Severe CHF left ventricular dysfunction Monitor body weight, fluid retention odema regularly Monitor liver function at baseline then monthly or as needed Monitor blood counts weekly for first 1 month, bi-monthly for 2nf month then periodically ( every 2-3 months )

Dosages/ Overdosage Etc:

Indication-

Chronic myeloid leukaemia Under specilalist supervision only chronic myeloid leukaemia-

Dosage-

400mg once daily with meals and large glass of water

Patient Information:

PATIENT COUNSELING INFORMATION

1. Dosing and Administration

Patients should be informed to take Gleevec exactly as prescribed, not to change

their dose or to stop taking Gleevec unless they are told to do so by their doctor.

If patients miss a dose they should be advised to take their dose as soon as possible

unless it is almost time for their next dose in which case the missed dose should

not be taken. A double dose should not be taken to make up for any missed dose.

Patients should be advised to take Gleevec with a meal and a large glass of water.

2. Pregnancy and Breast-Feeding

Patients should be advised to inform their doctor if they are or think they may be

3. Adverse Reactions

Patients should be advised to tell their doctor if they experience side effects during

Gleevec therapy including fever, shortness of breath, blood in their stools,

jaundice, sudden weight gain, symptoms of cardiac failure, or if they have a

history of cardiac disease or risk factors for cardiac failure.

4. Drug Interactions

Patients should be advised not to take any other medications, includin

over-the-counter medications such as acetaminophen or herbal products

without talking to their doctor or pharmacist first. Examples of other medications

that should not be taken with Gleevec are warfarin, erythromycin, and phenytoin.

5.Patients should also be advised to tell their doctor if they are taking or plan to

take iron supplements.

6.Patients should also avoid grapefruit juice and other foods known to inhibit

CYP3A4 while taking Gleevec.

Pharmacology/ Pharmacokinetics:

CLINICAL PHARMACOLOGY

1. Mechanism of Action

Imatinib mesylate is a protein-tyrosine kinase inhibitor that inhibits the bcr-abl tyrosine

kinase, the constitutive abnormal tyrosine kinase created by the Philadelphia

chromosome abnormality in CML. Imatinib inhibits proliferation and induces

apoptosis in bcr-abl positive cell lines as well as fresh leukemic cells from

Philadelphia chromosome positive chronic myeloid leukemia.

Imatinib inhibits colony formation in assays using ex vivo peripheral blood

and bone marrow samples from CML patients.

2. Pharmacokinetics

The pharmacokinetics of Gleevec have been evaluated in studies in healthy

subjects and in population pharmacokinetic studies in over 900 patients.

The pharmacokinetics of Gleevec are similar in CML and GIST patients.

Imatinib is well absorbed after oral administration with Cmax achieved within

2-4 hours post-dose. Mean absolute bioavailability is 98%.

Following oral administration in healthy volunteers, the elimination half-lives

of imatinib and its major active metabolite, the N-demethyl derivative (CGP74588),

are approximately 18 and 40 hours, respectively

Pregnancy and lactation:

USE IN SPECIFIC POPULATIONS

1. Pregnancy

Pregnancy Category D

2. Nursing Mothers

It is not known whether imatinib mesylate or its metabolites are excreted in human milk.

Because many drugs are excreted in human milk and because of the potential

for serious adverse reactions in nursing infants from Gleevec, 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

Gleevec safety and efficacy have been demonstrated in children with newly

diagnosed Ph+ chronic phase CML and in children with Ph+ chronic phase

CML with recurrence after stem cell transplantation or resistance to

interferon-alpha therapy. There are no data in children under 2 years of age.

Follow-up in children with newly diagnosed Ph+ chronic phase CML is limited.

As in adult patients, imatinib was rapidly absorbed after oral administration

in pediatric patients, with a Cmax of 2-4 hours.

4. Geriatric Use

In the CML clinical studies, approximately 40% of patients were older than 60 years

and 10% were older than 70 years. In the study of patients with newly diagnosed

CML, 22% of patients were 60 years of age or older.

No difference was observed in the safety profile in patients older than 65 years

as compared to younger patients, with the exception of a higher frequency

of edema

The efficacy of Gleevec was similar in older and younger patients.

No obvious differences in the safety or efficacy profile were noted in patients

older than 65 years as compared to younger patients, but the small number of

patients does not allow a formal analysis.

ALTANIB

Drug Interaction

Indication

Adverse Reaction

Contra-Indications

Dosages/ Overdosage Etc

Patient Information

Pharmacology/ Pharmacokinetics

Pregnancy and lactation