IMATIB 400MG

Description

Imatib 400mg is used as monotherapy, or it may combine with some other medicine in the conditions of certain types of cancer or bone marrow disorders.

PDG-derived tyrosine kinase that is expressed in the gastrointestinal stromal tumor.

Imatib 400mg indicated for

Imatib 400mg tablet is an anti-neoplastic medicine which is used in the treatment of;

• Advanced myelogenous leukemia (CML),
• Gastrointestinal stromal tumors (GISTs) and several malignancies
• Myelodysplastic/myeloproliferative disease
• Chronic Myeloid Leukemia
• Dermatofibrosarcoma protuberans
• Mastocytosis

How Imatib 400mg tablets work

Imatib contains an active component known as Imatinib mesylate; it is an inhibitor of certain tyrosine kinase enzymes.

Imatib prohibits BCR-ABL tyrosine

Imatib obstruct the multiplication and promote the apoptosis in BCR-ABL positive cells in addition to fresh leukemia cells from Philadelphia chromosome positive CML

Imatib also inhibits tumor growth of BCR-ABL transacted murine myeloid cells along other BCR-ABL positive leukemia CML in blast crisis

Imatib inhibits receptor tyrosine kinase for platelet-derived growth factor (PDGF), stem cell factor (SCF) and PDGF and SCF mediated cellular events get prohibited.

• Imatib a 2-phenylaminopyrimidine analog, it acts as a prohibition of the tyrosine kinase enzyme.
• In malignancy conditions, Philadelphia chromosome leads to the fusing of protein with BCR (breakpoint cluster region). Imatib used to reduced Bcr-Abl activity

Absorption

it is absorbed within 2-4 hours and bioavailability of Imatib 400mg tablets is about 98%.

Distribution

Imatib 400mg tablet has Human plasma protein bound almost range of 95%.

Metabolism

Imatib 400mg tablet Active metabolite is N-demethylated piperazine derivative. The enzyme which is responsible for metabolism of Imatib 400mg tablet is CYP3A4.

Excretion

The elimination of Imatib400mg through feces                                                                                                                  

The total drug excreted through feces 81% and drug through urine 13% with 7 days

The half lifetime of Imatib and active metabolite N-dimethyl derivative are around 18 and 40 hours respectively

Dosage and administration

The usual dose of tablet Imatib is 400mg or 600mg as a single dose. Whereas 800mg given by dividing the dose into two as 400mg twice daily.

Imatib tablets should be taken with food

The usual dose for following conditions;

Chronic myeloid leukemia

Chronic phase: In newly diagnosed patients, the dose of Imatib 400mg tablet is 400mg should be orally taken as a single dose.

If the failure of the chronic phase of the treatment with interferon alpha therapy; dose is raised to 600mg per day.

Quick phase: 600mg PO q Day; dose variation to 400mg PO as twice in a day if there is no serious adverse drug reaction or non-leukemia associated neutropenia or thrombocytopenia.

Gastrointestinal stromal tumors

The prescribed dose of the tablet Imatib 400mg is 400mg should be taken orally as a twice daily

Hyperesinophillic syndrome

In this condition, the recommended dose is 400mg PO q Day

Acute lymphoblastic leukemia

In adults, the prescribed dose is 600mg should be taken orally as a single dose.

Myelodysplastic/Myeloproliferative diseases

The usual dose is 400mg PO q Day

Dermatofibrosarcoma protuberans

Recommended dose is 400mg PO q12hr

In pediatric

Chronic myeloid leukemia

<1 year: the safety and efficacy of the drug has not been established

≥1 year: 340mg/m²/day PO; should not be exceed 600mg/day

Acute lymphoblastic leukemia

Patients<1 year: the safety and efficacy of the drug has not been established

Patients≥1 year: 340mg/m²/day PO; should not be exceed 600mg/day

Imatib 400mg tablet causes some side effects

Side effects are common in patients administrating Imatib 400mg-30%

• Nausea and vomiting
• Edema (swelling of the face, feet, hands)
• Muscle cramps and bone pain
• Diarrhea
• Haemorrhage
• Skin rash
• Fever
• Decreased blood counts

Less common side effects occur in patients administrating 10-29%

• Headache
• Fatigue
• Joint pain
• Indigestion (see heartburn)
• Abdominal pain
• Cough
• Shortness of breath
• Poor appetite
• Constipation
• Night sweats (see skin reactions)
• Nose bleeds (see bleeding problems)
• Weakness
• Affect ability to conceive or father a child

Drug – drug interaction

Warfarin is metabolized by CYP2C9 & CYP2A4, so patients who are taking anticoagulation therapy with Imatib, should take low molecular weight or standard heparin in reverse of warfarin.

Drug which inhibits the CYP3A4 activity may have chance to reduce metabolism and elevates the plasma concentration of Imatib frequently.

Concomitant use of St. John’s wort with Imatib causes decreasing AUC of Imatib to 30%. To avoid this problem, the dosage of Imatib increases up to 1200mg /day (600mg as two times a day).

While interaction of Imatib with strong inducers of CYP3A4, the dose of Imatib 400mg increased to 50%. If used with CYP3A4 strong inducers the AUC of Imatib 400mg decreases to 73%.

Combination of Imatib 400mg with strong CYP3A4 inhibitors; increase the risk of Imatib. Avoid these co administrations like Imatib 400mg with ketoconazole, itraconazole, clarithromycin, atazanavir, indinavir, ritonavir, voriconazole etc.

Interaction of Imatib 400mg with CYP3A4 substrates like alfentanil, cyclosporine, ergotamine, fentanyl, sirolimus or Tacrolimus causes low therapeutic effects. Imatib elevates the plasma concentration of CYP3A4 metabolized drugs like lipid lowering, calcium channel blockers etc.

Contraindication

Hypersensitive reaction to Imatib 400mg and other excipients presents in Imatib 400mg tablets.

Precaution

Avoid combination of strong CYP3A4 inducers

If anticoagulation is necessary, use LMW or standard heparin instead of warfarin

Gastrointestinal disorders: To avoid this problem, Imatib should be taken with food and large glass of water.

Hyperesinophillic cardiac toxicity

Dermatological toxicities

Hypothyroidism: Levothyroxine replacement therapy recommended; TSH level of the patients should be monitored periodically.  

Fluid retention and edema: The major damage of Imatib is fluid collection which may causes edema majorly superficial edema has been reported. To overcome these problem patients may frequently monitor for manifestation of fluid retention.

Hematological toxicity: Neutropenia, thrombocytopenia, anemia are the major blood related problems. To avoid these conditions, monitor the patients periodically with counting blood cell counts weekly for one month, two weeks for two months.

Serious congestive heart failure and left ventricular dysfunction: Patients who have cardiac problems should be monitored frequently.

Hepatotoxicity: Liver function test should be taken periodically to overcome these problems.

Pregnancy

Pregnancy category: D

Imatib 400mg will cause fetal harm when given to pregnant women

No clinical studies regarding use of drug in pregnant women

Lactations

Imatib 400mg should not recommended to pregnant and breast-feeding mothers, it can able to cause fetal malformations and cause fetal harm

The metabolites excreted in human milk.

Storage condition

Imatib 400mg tablet container should be stored in cool and dry place

It should be kept away from moisture, heat and light

Missed dose

If patient missed to take Imatib 400mg tablet, patient should have administered within a time. Otherwise, tablet should be discontinued and follow the next drug schedule.

Consult the doctor as soon as possible.