Imatinib Mesylate 400mg Tablets

Imatinib is a small molecule tyrosine kinase inhibitor that selectively inhibits the Bcr-Abl tyrosine kinase, which is the oncogenic driver in Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) and acute lymphoblastic leukemia (ALL). It also inhibits the receptor tyrosine kinases c-Kit (CD117) and platelet-derived growth factor receptor (PDGFR), which are implicated in gastrointestinal stromal tumors (GIST) and other conditions.

Urgent Side Effects: Seek Medical Help Right Away

While rare, some people may experience severe and potentially life-threatening side effects when taking this medication. If you notice any of the following symptoms, contact your doctor or seek medical attention immediately:

Allergic reactions: Rash, hives, itching, red, swollen, blistered, or peeling skin with or without fever, wheezing, tightness in the chest or throat, trouble breathing, swallowing, or talking, unusual hoarseness, or swelling of the mouth, face, lips, tongue, or throat.
Infections: Fever, chills, severe sore throat, ear or sinus pain, cough, increased or changed sputum production, painful urination, mouth sores, or unhealing wounds.
Bleeding: Vomiting or coughing up blood, coffee ground-like vomit, blood in urine, black, red, or tarry stools, gum bleeding, abnormal vaginal bleeding, unexplained bruises or enlarging bruises, or uncontrollable bleeding.
Electrolyte problems: Mood changes, confusion, muscle pain, cramps, or spasms, weakness, shakiness, balance changes, abnormal heartbeat, seizures, loss of appetite, or severe nausea and vomiting.
Kidney problems: Inability to urinate, changes in urine production, blood in urine, or significant weight gain.
Cardiovascular issues: Chest pain or pressure.
Neurological symptoms: Abnormal burning, numbness, or tingling sensations.
Vision changes: Changes in eyesight, eye pain, or severe eye irritation.
Depression.
Bone pain.

This medication may cause fluid retention, leading to swelling, weight gain, or breathing difficulties. If you experience any of these symptoms, inform your doctor.

Heart Failure: This medication may increase the risk of heart failure or worsen existing heart disease. If you have heart disease, inform your doctor. Seek immediate medical attention if you experience shortness of breath, significant weight gain, abnormal heartbeat, or new or worsening swelling in your arms or legs.

Liver Problems: This medication may cause severe and potentially life-threatening liver damage. Contact your doctor immediately if you notice dark urine, fatigue, decreased appetite, nausea, stomach pain, light-colored stools, vomiting, or yellow skin and eyes.

Tumor Lysis Syndrome (TLS): Patients with cancer taking this medication may be at increased risk of developing TLS, a potentially life-threatening condition. Seek medical attention immediately if you experience rapid or abnormal heartbeat, fainting, difficulty urinating, muscle weakness or cramps, nausea, vomiting, diarrhea, or loss of appetite.

Severe Skin Reactions: This medication may cause severe skin reactions, including Stevens-Johnson syndrome (SJS) and other serious conditions that can affect internal organs and be life-threatening. Seek medical help immediately if you notice red, swollen, blistered, or peeling skin; red or irritated eyes; sores in your mouth, throat, nose, eyes, genitals, or skin; fever; chills; body aches; shortness of breath; or swollen glands.

Other Side Effects

Most people taking this medication will not experience severe side effects, but some may encounter mild or moderate side effects. If you experience any of the following, contact your doctor or seek medical attention if they bother you or persist:

Hair loss
Muscle spasms
Dizziness, drowsiness, fatigue, or weakness
Sleep disturbances
Gas
Headache
Dry skin
Watery eyes
Changes in taste
Nose or throat irritation
Back, muscle, joint, arm, or leg pain
Weight gain
Night sweats
Anxiety
Stomach pain or heartburn
Constipation, diarrhea, nausea, vomiting, or decreased appetite (common side effects; consult your doctor for ways to manage them)

If any of these side effects bother you, do not improve, or are severe, contact your doctor.

Reporting Side Effects

This is not an exhaustive list of potential side effects. If you have questions or concerns, contact your doctor. You can also report side effects to the FDA at 1-800-332-1088 or online at https://www.fda.gov/medwatch.

Before Taking This Medication: Important Information to Share with Your Doctor

It is essential to inform your doctor about the following:

Any allergies you have, including allergies to this medication, its components, or other substances, such as foods or drugs. Be sure to describe the allergic reaction you experienced.
If you are currently taking warfarin.
If you are taking any of the following medications: carbamazepine, dexamethasone, phenobarbital, phenytoin, rifabutin, rifampin, or St. John's wort.
If you are breastfeeding. Note that you should not breastfeed while taking this medication or for 1 month after your last dose.

This list is not exhaustive, and it is crucial to discuss all your medications (including prescription, over-the-counter, natural products, and vitamins) and health issues with your doctor and pharmacist. They will help determine if it is safe for you to take this medication with your other medications and health conditions. Do not start, stop, or change the dosage of any medication without first consulting your doctor.

It is essential to inform all your healthcare providers, including doctors, nurses, pharmacists, and dentists, that you are taking this medication. Before engaging in activities that require alertness or clear vision, such as driving, wait until you understand how this drug affects you.

Regular blood tests and other laboratory evaluations, as directed by your doctor, are crucial to monitor your health while taking this medication. Additionally, avoid consuming grapefruit and grapefruit juice, as they may interact with this drug.

This medication may suppress the bone marrow's ability to produce necessary blood cells, potentially leading to bleeding problems, infections, or anemia if blood cell counts become severely low. If you have concerns, discuss them with your doctor.

You may be more susceptible to infections; therefore, practice good hygiene by washing your hands frequently and avoiding close contact with individuals who have infections, colds, or flu.

Be cautious, as this medication may increase your risk of bleeding easily. To minimize this risk, use a soft toothbrush and an electric razor. If you have had your thyroid removed, consult your doctor about the need for more frequent blood tests.

Before receiving any vaccinations, consult your doctor, as certain vaccines may not be effective or may increase the risk of infection when used with this medication.

You may be more prone to sunburn; thus, avoid excessive sun exposure, sunlamps, and tanning beds. Use protective measures such as sunscreen, clothing, and eyewear to safeguard against the sun.

There is a risk of severe and potentially life-threatening gastrointestinal tract perforation associated with this medication. Discuss this risk with your doctor.

If you are 65 years or older, use this medication with caution, as you may be more likely to experience side effects.

In some cases, this drug may affect growth in children and teenagers, necessitating regular growth assessments. Consult your doctor to discuss this potential risk.

This medication may harm an unborn baby. A pregnancy test will be conducted before initiating treatment to confirm that you are not pregnant. If you may become pregnant, use effective birth control during treatment and for at least 2 weeks after your last dose. If you become pregnant, notify your doctor immediately.

• Strong CYP3A4 inducers (e.g., rifampin, phenytoin, carbamazepine, phenobarbital, St. John's Wort): May significantly decrease imatinib plasma concentrations, leading to loss of efficacy. Concomitant use generally avoided.
• Strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, clarithromycin, ritonavir, grapefruit juice): May significantly increase imatinib plasma concentrations, increasing risk of toxicity. Consider dose reduction of imatinib or alternative agents.
• Warfarin and other coumarin derivatives: Imatinib may increase anticoagulant effect, leading to increased bleeding risk. Monitor INR closely and adjust anticoagulant dose.

• CYP3A4 substrates (e.g., cyclosporine, pimozide, triazolobenzodiazepines, dihydropyridine calcium channel blockers, simvastatin): Imatinib is a moderate inhibitor of CYP3A4, may increase concentrations of co-administered drugs metabolized by CYP3A4. Monitor for increased toxicity of these drugs.
• Proton pump inhibitors (PPIs) and H2-receptor antagonists: May reduce gastric pH, potentially decreasing imatinib solubility and absorption. Take imatinib with food and water; separate administration if possible, or consider alternative acid-reducing agents if clinically necessary.
• Levothyroxine: Hypothyroidism has been reported in patients taking imatinib after thyroidectomy and on levothyroxine replacement. Monitor TSH levels.

• Paracetamol (acetaminophen): Limited data, but theoretical interaction due to hepatic metabolism. Monitor for increased toxicity if high doses of paracetamol are used chronically.

• Unusual bleeding or bruising
• Fever, chills, or other signs of infection
• Unexplained fatigue or weakness
• Yellowing of skin or eyes (jaundice)
• Dark urine or pale stools
• Nausea, vomiting, diarrhea, abdominal pain
• Swelling (especially around eyes, ankles, hands), rapid weight gain
• Shortness of breath, cough, chest pain
• Muscle cramps or spasms
• Skin rash or itching

Imatinib can cause fetal harm when administered to a pregnant woman. Based on animal studies and human data, imatinib is associated with an increased risk of major birth defects and miscarriage. Use only if the potential benefit justifies the potential risk to the fetus. Women of childbearing potential should be advised to avoid pregnancy and use effective contraception during treatment and for at least 14 days after the last dose.

Imatinib and its active metabolite are excreted into human milk. Due to the potential for serious adverse reactions in the breastfed infant, breastfeeding is contraindicated during treatment with imatinib and for at least 14 days after the last dose.

Imatinib is approved for use in pediatric patients with Ph+ CML (chronic phase) and Ph+ ALL. Dosing is based on body surface area. Pediatric patients may experience similar adverse effects as adults, including myelosuppression, fluid retention, and growth retardation. Growth should be monitored in children receiving imatinib.

No specific dose adjustment is required based on age alone. However, elderly patients may be more susceptible to certain adverse effects, such as fluid retention and myelosuppression. Monitor closely for adverse reactions.

• Always take imatinib with food and a large glass of water to minimize GI upset and improve absorption.
• Monitor patients closely for fluid retention (edema, pleural effusion, ascites), especially during the first year of treatment. Diuretics may be needed, and dose reduction or interruption may be necessary in severe cases.
• Regular monitoring of CBC and LFTs is crucial due to the risk of myelosuppression and hepatotoxicity.
• Imatinib is a substrate and inhibitor of CYP3A4; significant drug interactions are possible with strong CYP3A4 inducers/inhibitors and other CYP3A4 substrates.
• Patients should be advised to avoid grapefruit and St. John's Wort.
• Consider the potential for cardiac dysfunction, especially in patients with pre-existing cardiac conditions or risk factors.
• For patients with difficulty swallowing, the tablets can be dispersed in a glass of water or apple juice (for 400 mg tablets, 200 mL water/juice; for 100 mg tablets, 50 mL water/juice). Stir until completely dispersed and drink immediately.

• Other BCR-ABL tyrosine kinase inhibitors for CML: Dasatinib, Nilotinib, Bosutinib, Ponatinib (for resistant/intolerant CML)
• Chemotherapy (for certain indications or in combination)
• Allogeneic hematopoietic stem cell transplantation (for CML, especially in advanced phases or failure of TKI therapy)

If your symptoms or health issues persist or worsen, it is essential to contact your doctor promptly. To ensure safe and effective treatment, never share your medication with others or take someone else's medication. Some medications may come with an additional patient information leaflet, so it's a good idea to check with your pharmacist for more information. If you have any questions or concerns about your medication, don't hesitate to reach out to your doctor, nurse, pharmacist, or other healthcare provider. In the event of a suspected overdose, immediately call your local poison control center or seek emergency medical attention. When seeking help, be prepared to provide details about the medication taken, the amount, and the time it happened.