Imatinib

BRAND NAME:

Gleevec – Gleevac is a composition of imatinib mesylate with strengths of 100mg & 400mg which is available as an oral tablet.

MECHANISM OF ACTION:

Imatinib mesylate is a protein and tyrosine kinase inhibitor with a 2-phenylamino-pyrimidine derivative initially designed to target the platelet-derived growth factor receptor. It also inhibited other protein tyrosine kinases, including c-kit and the BCR-ABL fusion protein. These protein tyrosine kinases phosphorylate certain amino acids on substrate proteins, causing signal transmission and changes in cell biology, such as cell growth and death, which are constitutively activated by mutations or other alterations. Imatinib inhibits the constitutive action of a protein tyrosine kinase competitive inhibitor of the ATP binding cleft of ABL, causing leukemic cells to undergo death.

PHARMACOKINETICS:

Absorption: Imatinib is well absorbed and has a 98% absolute bioavailability when taken orally. The terminal elimination half-life is about eight hours. When attaining a steady state, imatinib plasma concentrations increase by two to threefold. 

Distribution: The protein plasma binding rate is approximately 95%. 

Metabolism: It is mostly metabolized by the cytochromes CYP450, CYP3A4, and CYP3A5, and it can hinder the metabolism of medications that are CYP3A4 or CYP3A5 substrates. 

Excretion: The medication is primarily removed through bile in the form of metabolites. The fecal-to-urinary excretion ratio is roughly 5:1.

PHARMACODYNAMICS:

Imatinib is a 2-phenylamino pyrimidine derivative that belongs to tyrosine kinase inhibitors. It is quite selective towards the BCR-ABL fusion protein present in various cancers. The BCR-ABL pathway controls the cellular proliferation, cellular motility, and apoptosis pathways.

DOSAGE AND ADMINISTRATION:

These are available in oral tablets with strengths of 100mg and 400mg. The dose prescribed will be different for different patients. The amount of medicine recommended depends on the strength of the medicine, the number of doses you take each day, the time allowed between doses, and depending on the medical problem for which medicine you are taking.

•  For the treatment of myelodysplastic syndrome or myeloproliferative disease, the recommended dose for adults is 400mg once a day.

•  The dose recommended for the treatment of chronic eosinophilic leukemia or hypereosinophilic syndrome in adults is 400mg once a day.

•  In the treatment of gastrointestinal stromal tumors the dosage recommended in adults is 400mg once a day.

•  For the treatment of dermatofibrosarcoma protuberans in adults the dose given is 800mg per day as a single dose or divided as 400mg 2 times per day.

•  In adults 400mg once a day is recommended in treating aggressive systemic mastocytosis.

•  For Philadelphia chromosome-positive acute lymphoblastic leukemia, the dose recommended is 600mg once a day.

• In Philadelphia chromosome-positive chronic myeloid leukemia treatment the dose recommended is 400mg once a day.

The children above 1 year of age and older, the dose will depend on body size and must be determined by the doctor.

DRUG INTERACTIONS:

The drugs that can cause toxicity when interacted with imatinib are mentioned below

•  Levothyroxine

•  Seizure medicines

•  Ketoconazole and clarithromycin

•  Dexamethasone

•   Paracetamol

•  Proton pump inhibitors

•  Blood thinners

•   Iron-content medicines

•  Antibiotics, antifungals and antiviral medicines

FOOD INTERACTIONS:

Avoid eating grapefruits and grapefruit juices while taking this medication.

ADVERSE EFFECTS:

•  Gastrointestinal disorders

•  Growth retardation in children

•  Hepatotoxicity

•  Growth retardation

•  Tumor lysis syndrome

•   Embryo-fetal toxicity

•   Bone pains

•   Swelling around eyes, hands, feet, ankles or lower legs

•   Shortness of breath

•   Coughing with bloody mucus

•   Chest pain

•   Anemia

•   Blood in stools

•   Increased urination

•    Irregular heartbeat

•    Unusual bruising or bleeding

•    Joint swelling

•    Prickling feeling on the skin

•    Fever

•    Abdominal pain

•    Bloating

•    Hypokalemia

•    Indigestion or heartburn

•    Hair loss

•   Teary eyes

•    Muscle cramps

•    Nail changes

•    Tingling

•    Burning

•    Dry mouth

•    Pink eye

TOXICITY:

In case of overdose taken then the prescribed dose leads to some toxic effects.

Symptoms of overdose

•  Seizures

•  Nausea

•   Muscle cramps

•   Vomiting

•   Diarrhea

•   Abdominal pain

•   Extreme tiredness

•    Loss of appetite

•   Muscle cramps

should not be taken when expecting since the fetus could be harmed. Wearing a high sun protection factor outdoors is crucial since imatinib may cause the patient to become more sensitive to the sun. Before using this medication, a patient with a history of hepatitis B infection should speak with their physician because it may cause the condition to relapse.

STORAGE:

Store medication at room temperature 15℃ and 30℃ (59℉ and 86℉). Keep tightly in a closed container.