How imatinib works
As a so-called BCR-ABL kinase inhibitor, imatinib inhibits an enzyme that is overactive in cancer cells. The activity of this tyeosin kinase is thereby downregulated so that it again corresponds to that in healthy cells.
Because healthy cells do not have this pathologically altered enzyme, imatinib only works on cancer cells. The risk of side effects is therefore lower than with older cancer drugs (non-specific cytostatics), which generally act against rapidly dividing cells – regardless of whether they are healthy cells or cancer cells.
In the body, it is strictly regulated which cells must multiply and when, and when they must die. Most of the body’s tissues regenerate continuously in order to be able to withstand constant stress. Other tissues, such as nerve tissue, essentially do not divide or regenerate at all.
Before a cell divides, the genetic material (consisting of the 46 chromosomes) must be duplicated and then divided equally between the two daughter cells. If errors occur in the process and are not repaired, this can lead to cancer. This also happens in a special form of blood cancer, Philadelphia chromosome-positive chronic myeloid leukemia.
The excessive presence of white blood cells also leads to the name of the disease: “leukemia” translates as “white blood.
Absorption, degradation and excretion
After ingestion, imatinib is absorbed into the blood via the intestinal mucosa and reaches the diseased cells via transport proteins in the blood. In the liver, the active ingredient is partially converted, although the main conversion product is still effective against the cancer cells.
About three-quarters of the drug is converted and degraded. The degradation products and the unchanged imatinib are mainly excreted in the stool. After 18 hours, only about half of the active ingredient is still in the body.
When is imatinib used?
Imatinib is used to treat newly diagnosed Philadelphia chromosome-positive chronic myeloid leukemia in adults and children when certain conditions are met (such as a bone marrow transplant is not possible or treatment with interferons has not been successful).
The duration of treatment with imatinib depends on the type and severity of the disease and is determined by the physician. In most cases, imatinib therapy is given long-term as a continuous treatment to suppress the growth and especially the spread of the tumor.
How imatinib is used
Imatinib is taken in the form of tablets. The dosage is usually 400 to 600 milligrams of imatinib once a day with a meal and a glass of water. In particularly severe cases of disease or flare-ups, 800 milligrams divided into two doses (morning and evening) is taken with meals.
Children receive appropriately lower daily imatinib doses. For patients with dysphagia and children under six years of age, the imatinib tablet may be crushed, slurped in non-carbonated water or apple juice, and then drunk.
What are the side effects of imatinib?
The most commonly reported side effects in more than ten percent of patients are mild nausea, vomiting, diarrhea, abdominal pain, headache, fatigue, muscle cramps and pain, and skin flushing. Water retention in the tissues may also occur, especially around the eyes and in the legs.
What should be considered when taking imatinib?
Contraindications
Imatinib must not be taken by:
- Hypersensitivity to the active substance or to any of the other components of the drug.
Drug interactions
Because imatinib is broken down in the liver by enzymes that also break down other active ingredients, there may be interactions when it is taken at the same time – even if the drugs are taken at different times of the day.
Some drugs can inhibit the degradation of imatinib, for example various antibiotics (such as erythromycin, clarithromycin), HIV drugs (such as ritonavir, saquinavir) and drugs against fungal infections (such as ketoconazole, itraconazole).
Other drugs accelerate the breakdown of imatinib, causing the cancer drug to work less effectively or not at all. Such drugs include glucocorticoids (“cortisone” such as dexamethasone) and epilepsy drugs (such as phenytoin, carbamazepine, phenobarbital).
Patients with coagulation disorders receiving coumarins such as phenprocoumon or warfarin are usually switched to heparin during treatment with imatinib. Heparins, unlike coumarins, are injected rather than ingested. They can be quickly rendered ineffective by the physician with an antidote if bleeding occurs.
Driving and Operating Heavy Machinery
During imatinib treatment, patients should operate heavy machinery and drive motor vehicles only with caution.
Age Limitation
Imatinib has been approved for use in children.
Pregnancy and Lactation
Available data on the use of imatinib in pregnancy are limited. Anecdotal post-marketing reports indicate that the drug may cause miscarriage or birth defects when a pregnant woman is treated with it.
Imatinib should therefore not be administered, according to the SmPC, because the drug may harm the child. If treatment is absolutely necessary, the expectant mother must be informed of the possible risk to the fetus.
Limited information is also available for the lactation period. Studies in two breastfeeding women have shown that imatinib and its active metabolite pass into breast milk. Therefore, to be on the safe side, women should not breastfeed for at least 15 days after the last dose.
How to get medicines with imatinib
Preparations containing the active ingredient imatinib are available on prescription in Germany, Austria and Switzerland in every dosage and package size.
Since when is imatinib known?
In the meantime, generic drugs with the active ingredient imatinib have also been approved.