Gleevec

Gleevec (imatinib) is a drug that belongs to a class of drugs called tyrosine kinase inhibitors. It is used to treat various forms of cancer, such as chronic myeloid leukemia (CML), gastrointestinal stromal tumor (GIST), and other diseases associated with excess tyrosine kinase activity. Gleevec works by blocking signaling pathways in cells that allow them to grow and multiply inappropriately. This helps control the growth of cancer cells and slow down the progression of cancer.

Indications Gleevec

1. Chronic myeloid leukemia (CML) in chronic phase, accelerated phase or blast crisis.
2. Gastrointestinal stromal tumor, if the tumor cannot be completely removed by surgery or if metastases are present.
3. Dermatofibrosarcoma of the ducts.

Release form

Gleevec usually comes as a tablet to take by mouth.

Pharmacodynamics

• Gleevec is a tyrosine kinase inhibitor that acts on tyrosine kinases associated with certain oncogenes. Specifically, it inhibits the BCR-ABL tyrosine kinase, which is commonly associated with CML, as well as other tyrosine kinases such as PDGFR (platelet cell growth factor) and KIT (tyrosine kinase receptor).
• Blocking the activity of these tyrosine kinases helps interrupt signaling pathways that promote tumor growth and development, resulting in inhibition of tumor growth and a reduction in tumor mass.

Pharmacokinetics

1. Absorption: Gleevec is generally rapidly and completely absorbed from the gastrointestinal tract after oral administration. Peak plasma concentrations are usually reached 2-4 hours after administration.
2. Metabolism: Imatinib is metabolized in the liver via cytochrome P450 enzymes. The main metabolites are the active forms, N-demethyl-imatinib and N-oxide-imatinib.
3. Excretion: Gleevec and its metabolites are excreted primarily in the bile (approximately 68%) and urine (approximately 13%). The urinary excretion rate is approximately 10% unchanged.
4. Elimination half-life: The half-life of Gleevec in the body is about 18 hours, which means the drug can be taken once or twice a day to ensure stable blood levels.
5. Food: Taking Gleevec with food may decrease its absorption, so it is generally recommended to take it on an empty stomach or 1-2 hours before meals.
6. Drug interactions: Gleevec may interact with certain other drugs, particularly those that are also metabolized via cytochrome P450 enzymes. Interactions may affect the effectiveness or safety of treatment.

Dosing and administration

1. Directions for use:

   • Gleevec is usually taken orally, that is, by mouth.
   • The tablets should be swallowed whole, without breaking or chewing, with a small amount of water.
   • It is recommended that you take your tablets at the same time each day to ensure stable concentrations of the drug in your blood.

2. Dosage:

   • The dosage of Gleevec may vary depending on the type of cancer and the stage of the disease.
   • The usual starting dose for adults with chronic myeloid leukemia (CML) is 400 mg per day.
   • For patients with other forms of cancer or depending on the progression of the disease, the dose may be changed by the doctor.

3. Duration of admission:

   • The duration of treatment with Gleevec is determined by your doctor and depends on your response to treatment and the characteristics of your disease.
   • Treatment may continue for a long time and the drug is usually taken under constant medical supervision.

Use Gleevec during pregnancy

Use of Gleevec during pregnancy is associated with a risk of birth defects and other serious problems, so its use is not recommended unless strictly medically indicated and under close medical supervision. Here are some key findings from the studies:

1. Risks to the fetus: Gleevec may cause birth defects, especially when used in the first trimester of pregnancy. A study found that 50% of pregnancies exposed to imatinib resulted in healthy babies, but 12 cases involved congenital anomalies, including complex malformations in three babies (Pye et al., 2008).
2. Case study: A woman with chronic myeloid leukemia was successfully treated with imatinib during the second and third trimesters of pregnancy and gave birth to a healthy baby with no congenital anomalies. However, imatinib was detected in the baby’s placental and peripheral blood, highlighting its ability to cross the placental barrier (Ali et al., 2009).

Due to potential risk to the fetus, it is recommended to avoid the use of imatinib during pregnancy, especially in the first trimester. If imatinib therapy is necessary for the treatment of the mother, a careful risk-benefit analysis should be performed and alternative treatments should be considered.

Contraindications

1. Hypersensitivity: People with a known hypersensitivity to imatinib or to any of the ingredients of the drug should not take Gleevec.
2. Heart problems: Gleevec may be contraindicated in patients with serious heart problems such as heart failure, arrhythmias, or past heart attacks.
3. Hepatic impairment: In patients with severe hepatic impairment, Gleevec should be used with caution and under medical supervision as it may increase the risk of liver dysfunction.
4. Kidney problems: Gleevec is metabolized primarily in the liver, but its metabolites may also be excreted through the kidneys. Patients with severe kidney impairment may require dosage adjustments.
5. Pregnancy and breastfeeding: There is limited information on the safety of Gleevec during pregnancy and breastfeeding, so its use during this period should be carried out only on the advice of a doctor.
6. Paediatric population: The efficacy and safety of Gleevec in children may not be fully studied, so its use in children may require consultation with a doctor.
7. Elderly: Elderly patients may require more careful prescribing and regular monitoring when using Gleevec.

Side effects Gleevec

1. Hepatotoxicity: Increased levels of liver enzymes in the blood, jaundice.
2. Cytopenia: A decrease in the number of blood cells such as white blood cells, platelets, and red blood cells.
3. Gastrointestinal disorders: Nausea, vomiting, diarrhea, dyspepsia, loss of appetite, liver dysfunction.
4. Osteoporosis: Decreased bone density and increased risk of fractures.
5. Gastrointestinal bleeding: Gastric ulcer and intestinal ulcer, bleeding.
6. Edema and fluid retention: Edema in various parts of the body, including the legs and face.
7. Myalgia and arthralgia: Pain in muscles and joints.
8. Cardiotoxicity: Increase or decrease in cardiac function.
9. Skin reactions: Rash, itching, skin rash.
10. Vision problems: Blurred vision, retinal detachment.

Overdose

1. Increased side effects such as nausea, vomiting, diarrhea, fatigue, headache, and others.
2. Serious complications may develop, such as myelosuppression (decrease in the number of blood-forming cells), hepatotoxicity (liver damage), and cardiac dysfunction.
3. Other rare and serious side effects may occur, including neurotoxicity and respiratory problems.

Interactions with other drugs

1. Cytochrome P450 inhibitors or inducers: Gleevec is metabolized in the liver via cytochrome P450 enzymes. Drugs that are strong inhibitors or inducers of these enzymes may alter the concentration of imatinib in the blood. For example, cytochrome P450 inhibitors such as ketoconazole may increase imatinib concentrations, while inducers such as rifampin may decrease them.
2. Drugs that affect gastrointestinal pH: Taking drugs that change gastrointestinal pH, such as antacids or drugs containing proton inhibitors, may affect the absorption of Gleevec. This may reduce its effectiveness.
3. Drugs that increase the risk of cardiotoxicity: Gleevec may increase the risk of cardiotoxicity when used with other drugs that may also have adverse effects on the cardiovascular system, such as antiarrhythmic drugs.
4. Drugs that increase the risk of myelosuppression: Gleevec may increase myelosuppression when used with other drugs that also affect blood formation, such as cytotoxic drugs or drugs used to treat cancer.
5. Medicines that increase the risk of bleeding: Gleevec may increase the risk of bleeding when used with anticoagulants or antiplatelet drugs.
6. Drugs that affect liver or kidney function: Drugs that affect liver or kidney function may alter the pharmacokinetics of imatinib and its metabolites.