Gleevec

Gleevec (imatinib) is a drug belonging to the class of 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 cause them to grow and multiply unexplained. This allows you to control the growth of cancer cells and slow down the progression of cancer.

Indications Gleeveka

1. Chronic myeloid leukemia (CML) in the 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. Ductal dermatofibrosarcoma.

Release form

Gleevec usually comes in tablet form to be taken orally.

Pharmacodynamics

• Gleevec is a tyrosine kinase inhibitor that targets tyrosine kinases associated with certain oncogenes. In particular, it inhibits the tyrosine kinase BCR-ABL, which is commonly associated with CML, as well as other tyrosine kinases such as PDGFR (plate cell growth factor) and KIT (receptor tyrosine kinase).
• 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 decrease in tumor mass.

Pharmacokinetics

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

Dosing and administration

1. Method of application:

   • Gleevec is usually taken orally, i.e. Through the mouth.
   • The tablets should be swallowed whole, without splitting or chewing, with a small amount of water.
   • It is recommended to take the tablets at the same time every day to ensure stable drug concentrations in the 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 your doctor.

3. Duration of treatment:

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

Use Gleeveka during pregnancy

The use of Gleevec during pregnancy is associated with the risk of birth defects and other serious problems, so its use is not recommended without strict medical indications and under close medical supervision. Here are some key findings from the research:

1. Risks to the fetus: Gleevec can cause birth defects, especially when used in the first trimester of pregnancy. The study found that 50% of pregnancies exposed to imatinib resulted in healthy babies, but 12 cases had congenital anomalies, including complex malformations in three newborns (Pye et al., 2008).
2. Case Study: A woman suffering from chronic myeloid leukemia was successfully treated with imatinib during the second and third trimesters of pregnancy and gave birth to a healthy baby without congenital anomalies. However, imatinib has been detected in the placental and peripheral blood of the child, highlighting its ability to cross the placental barrier (Ali et al., 2009).

Due to the potential risk of exposure 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 maternal treatment, 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 any of the ingredients of the drug should not take Gleevec.
2. Heart problems: Gleevec may be contraindicated in patients with serious heart disease, such as heart failure, arrhythmias, or previous heart attacks.
3. Liver impairment: In patients with severe hepatic impairment, Gleevec should be used with caution and under medical supervision as it may increase the risk of developing hepatic dysfunction.
4. Kidney problems: Gleevec is metabolized primarily in the liver, but its metabolites may also be excreted through the kidneys. Patients with severe renal impairment may require dosage adjustment.
5. Pregnancy and breastfeeding: Data on the safety of Gleevec during pregnancy and breastfeeding are limited, so its use during this period should only be done on the advice of a physician.
6. Children: The effectiveness and safety of Gleevec in children may not have been sufficiently studied, so its use in children may require consultation with a doctor.
7. Geriatric age: Elderly patients may require more careful prescribing and regular monitoring when using Gleevec.

Side effects Gleeveka

1. Hepatotoxicity: Increased levels of liver enzymes in the blood, jaundice.
2. Cytopenia: Decreased number of blood cells such as white blood cells, platelets and red blood cells.
3. Gastrointestinal disorders: Nausea, vomiting, diarrhea, dyspepsia, appetite, liver dysfunction.
4. Osteoporosis: Decreased bone density and increased risk of fractures.
5. Gastrointestinal bleeding: Peptic ulcer of the stomach and intestines, bleeding.
6. Swelling and fluid retention: Swelling in various parts of the body, including the legs and face.
7. Myalgia and arthralgia: Pain in muscles and joints.
8. Cardiotoxicity: Increased or decreased levels of cardiac function.
9. Skin reactions: Rash, itching, skin marks.
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 (decreased 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 alter gastrointestinal pH, such as antacids or drugs containing proton inhibitors, may affect the absorption of Gleevec. This may reduce its effectiveness.
3. Medicines 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. Medicines 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 affecting hepatic or renal function: Drugs that affect hepatic or renal function may alter the pharmacokinetics of imatinib and its metabolites.