Gleevec 400mg (scored) Tablets

Imatinib is a small molecule tyrosine kinase inhibitor that selectively inhibits the Bcr-Abl tyrosine kinase, which is the oncogenic driver in Chronic Myeloid Leukemia (CML) and Philadelphia chromosome-positive Acute Lymphoblastic Leukemia (Ph+ ALL). It also inhibits the receptor tyrosine kinases KIT (stem cell factor receptor) and PDGFRA (platelet-derived growth factor receptor alpha), which are involved in the pathogenesis of Gastrointestinal Stromal Tumors (GIST) and other diseases. By binding to the ATP-binding site of these kinases, imatinib prevents phosphorylation of the substrate, thereby inhibiting downstream signaling pathways involved in cell proliferation and survival.

Urgent Side Effects: Seek Medical Help Right Away

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

Signs of an allergic reaction: 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.
Signs of infection: fever, chills, severe sore throat, ear or sinus pain, cough, increased or changed sputum production, painful urination, mouth sores, or a wound that won't heal.
Signs of bleeding: vomiting or coughing up blood, coffee ground-like vomit, blood in the urine, black, red, or tarry stools, gum bleeding, abnormal vaginal bleeding, unexplained bruises or bruising that worsens, or uncontrollable bleeding.
Signs of 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.
Signs of kidney problems: inability to urinate, changes in urine production, blood in the urine, or significant weight gain.
Chest pain or pressure.
Abnormal burning, numbness, or tingling sensations.
Changes in vision, eye pain, or severe eye irritation.
Depression.
Bone pain.

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

Heart Failure and Liver Problems

Heart failure has occurred in patients taking this medication, including those with pre-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.
New or worsening swelling in the arms or legs.

Severe and potentially life-threatening liver problems have occurred with this medication. Contact your doctor immediately if you notice:

Dark urine.
Fatigue.
Decreased appetite.
Nausea or stomach pain.
Light-colored stools.
Vomiting.
Yellow skin or eyes.

Tumor Lysis Syndrome (TLS) and Severe Skin Reactions

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.
Urination difficulties.
Muscle weakness or cramps.
Nausea, vomiting, diarrhea, or loss of appetite.
Fatigue.

Severe skin reactions, including Stevens-Johnson syndrome (SJS) and other serious conditions, may occur with this medication. These reactions can be life-threatening and may affect internal organs. Seek medical help immediately if you notice:

Red, swollen, blistered, or peeling skin.
Red or irritated eyes.
Sores in the mouth, throat, nose, eyes, genitals, or skin.
Fever.
Chills.
Body aches.
Shortness of breath.
Swollen glands.

Other Side Effects

Most people taking this medication do not experience severe side effects. However, some may encounter mild or moderate side effects, including:

Hair loss.
Muscle spasms.
Dizziness, drowsiness, fatigue, or weakness.
Sleep disturbances.
Gas.
Headaches.
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.

If these side effects bother you, do not improve, or are severe, contact your doctor for guidance on managing them.

Reporting Side Effects

If you have questions or concerns about side effects, 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 symptoms 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 to take this medication with your other medications and health conditions. Never start, stop, or change the dose 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 operating a vehicle or engaging in activities that require alertness and clear vision, wait until you understand how this medication affects you.

Regularly undergo blood tests and other laboratory examinations as directed by your doctor to monitor your condition.

Avoid consuming grapefruit and grapefruit juice, as they may interact with this medication. Be aware that this drug can 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, consult 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.

This medication can increase your risk of bleeding easily. Exercise caution to prevent injuries, and use a soft-bristled toothbrush and an electric razor for shaving. If you have undergone thyroid removal, discuss your condition with your doctor, as you may require more frequent blood tests.

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

You may be more prone to sunburn; thus, limit your exposure to sunlight, sunlamps, and tanning beds, and use protective measures such as sunscreen, clothing, and eyewear.

Be aware that this medication can cause severe and potentially life-threatening gastrointestinal tract perforations. If you experience any unusual symptoms, consult your doctor promptly.

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

In some cases, this medication may affect growth in children and adolescents, and regular growth assessments may be necessary. Discuss this with your doctor.

This medication can cause harm to 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.

• Strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, clarithromycin, ritonavir) - may increase imatinib plasma concentrations, increasing risk of toxicity. Consider dose reduction of imatinib.
• Warfarin and other coumarin derivatives - imatinib may increase anticoagulant effect, increasing bleeding risk. Monitor INR closely.
• Simvastatin and other HMG-CoA reductase inhibitors (CYP3A4 substrates) - imatinib may increase their plasma concentrations, increasing risk of myopathy/rhabdomyolysis. Consider dose reduction of statin or alternative.
• Midazolam (CYP3A4 substrate) - imatinib increases midazolam AUC. Caution with other sensitive CYP3A4 substrates with narrow therapeutic index.

• Other CYP3A4 substrates (e.g., cyclosporine, tacrolimus, sirolimus, calcium channel blockers like dihydropyridines, some benzodiazepines) - imatinib may increase their concentrations. Monitor and adjust dose as needed.
• CYP2D6 substrates (e.g., metoprolol) - imatinib may increase their concentrations.
• Paracetamol (acetaminophen) - potential for increased hepatotoxicity when co-administered with imatinib, especially at high doses of paracetamol.

• Not available (interactions are generally categorized as major/moderate due to narrow therapeutic index or significant PK changes).

• Fluid retention/edema (especially periorbital, ankle swelling, sudden weight gain)
• Fatigue
• Nausea, vomiting, diarrhea
• Muscle cramps, musculoskeletal pain
• Rash
• Bleeding (unusual bruising, petechiae, GI bleeding)
• Signs of infection (fever, chills, sore throat)
• Shortness of breath, chest pain (potential cardiac or pulmonary toxicity)
• Yellowing of skin/eyes, dark urine, severe abdominal pain (signs of liver problems)

Imatinib can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to the fetus. Females of reproductive potential should be advised to use effective contraception during treatment and for at least 14 days after the last dose.

It is not known whether imatinib is excreted in human milk. Due to the potential for serious adverse reactions in breastfed infants, advise women not to breastfeed during treatment with imatinib and for at least 14 days after the last dose.

Imatinib is approved for pediatric patients with CML (chronic phase) and Ph+ ALL. Dosing is based on body surface area. Close monitoring for growth and development is recommended, as long-term effects are still being studied.

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

• Always take imatinib with food and a large glass of water to minimize gastrointestinal irritation.
• The 400mg scored tablet can be broken in half for dose adjustments (e.g., 200mg). For patients unable to swallow tablets, they can be dispersed in water or apple juice.
• Fluid retention (edema) is a very common side effect, especially periorbital edema. Monitor weight regularly and report significant weight gain or swelling.
• Myelosuppression (low blood counts) is also common and requires regular CBC monitoring and potential dose adjustments.
• Muscle cramps are a frequent complaint; magnesium supplementation may help in some cases.
• Imatinib is a substrate and inhibitor of CYP3A4, leading to numerous drug-drug interactions. Always review concomitant medications.
• Patients should be educated on signs of serious adverse events, particularly liver toxicity and severe skin reactions.

• Other BCR-ABL Tyrosine Kinase Inhibitors for CML: Dasatinib (Sprycel), Nilotinib (Tasigna), Bosutinib (Bosulif), Ponatinib (Iclusig), Asciminib (Scemblix).
• Other Tyrosine Kinase Inhibitors for GIST: Sunitinib (Sutent), Regorafenib (Stivarga).
• Chemotherapy (for certain indications where TKIs are not suitable or have failed).

If your symptoms or health issues persist or worsen, it's essential to contact your doctor for further guidance. To ensure your safety, never share your medication with others or take someone else's medication. Some medications may come with an additional patient information leaflet, so be sure to check with your pharmacist for more information. If you have any questions or concerns about this 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 medical attention. When seeking help, be prepared to provide details about the overdose, including the medication taken, the amount, and the time it occurred.