Letrozole

Benjamin Clanner-Engelshofen is a freelance writer in the medical department. He studied biochemistry and pharmacy in Munich and Cambridge / Boston (USA) and noticed early on that he particularly enjoyed the interface between medicine and science. That is why he went on to study human medicine.

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The active ingredient letrozole is a so-called non-steroidal aromatase inhibitor. It is used to treat breast cancer. The enzyme aromatase, which is inhibited by letrozole, ensures the conversion of hormone precursors to estrogens such as estradiol and estrone. These often stimulate the growth of breast cancer tumors. Here you can read everything you need to know about the effects and use of letrozole, side effects and interactions.

This is how letrozole works

During puberty, especially in women, breast tissue is stimulated to grow by estrogens. The cells in the breast therefore have a particularly large number of docking points (receptors) for the female hormones.

When such cells degenerate, the natural cell division limit is lifted. The cells begin to divide and multiply in an uncontrolled manner - breast cancer develops. Since the tumor cells in very many cases have estrogen receptors on their surface, they are stimulated to grow by normal blood levels of these female hormones.

The active ingredient letrozole inhibits the enzyme aromatase, which the body needs for the production of estrogens from the precursors testosterone and androstenedione. This lowers the level of estrogen. As a result, the malignant tumor in the breast is no longer stimulated to grow.

Letrozole is also used together with testosterone as a doping agent in weight training. The male sex hormone is used to build muscle and increase performance. But if there is too much testosterone in the body, some of it is converted into estrogen. This then leads to side effects such as breast growth in men (gynecomastia). Letrozole is supposed to prevent this: It prevents more testosterone from being converted into estrogen.

Letrozole uptake, breakdown and excretion

Once ingested, letrozole is quickly and completely absorbed in the intestines. The aromatase inhibitor is quickly transported into the tissue via the blood. From there it reaches the liver only slowly via the blood, where it is broken down. The liver enzymes involved convert letrozole into inactive breakdown products. Two to four days after ingestion, most of the active ingredient is excreted in the urine.

When is letrozole used?

The active substance letrozole is used in postmenopausal women alone or with other anti-cancer drugs to treat breast cancer if the tumor is promoted in its growth by estrogens (hormone-sensitive breast cancer). Letrozole can be used both as an initial therapy and as a follow-up therapy (usually after treatment with tamoxifen).

Treatment with letrozole usually lasts a few months (for example, to shrink a tumor before an operation) up to five years.

This is how letrozole is used

Letrozole is taken in the form of tablets. The usual dosage is two and a half milligrams of letrozole per day. It is taken once a day, independently of meals, with a glass of water.

If a dose of letrozole is forgotten in one day, it can be taken up to three hours before the next scheduled dose. If there are only three hours or less until the next scheduled dose, the forgotten tablet should not be taken in order to avoid high blood levels.

What are the side effects of letrozole?

During treatment with letrozole, more than one in ten patients experience undesirable effects such as high blood cholesterol, hot flashes, increased sweating and sweating, joint pain and tiredness with a feeling of weakness and discomfort.

One to ten percent of patients show letrozole side effects such as loss of or increased appetite, headache, dizziness, increased blood pressure, nausea, vomiting, indigestion, constipation, diarrhea, abdominal pain, hair loss, rashes and dry skin, bone and muscle pain, decreased bone density ( sometimes associated with broken bones), vaginal bleeding, fluid retention in various tissues, and weight gain.

The majority of these side effects only occur during the first few weeks of treatment and become less severe afterwards.

What should be considered when taking letrozole?

Treatment with letrozole should only be given to postmenopausal women. If it is unclear whether a woman has passed menopause or not, the doctor should check the blood levels of the relevant hormones (LH and FSH) before treatment is started.

In patients with severe liver dysfunction, the active substance letrozole may only be broken down and excreted more slowly. In clinical studies, the elimination time has roughly doubled compared to women with healthy liver. Since there is a risk that the active ingredient will then accumulate in the body, the blood level of the drug should be closely monitored in these patients if necessary.

Letrozole can have a negative effect on bone density and thus on bone strength. Therefore, bone density should be checked regularly in women with risk factors or pre-existing osteoporosis. It may be necessary to take additional medication to increase bone density.

The simultaneous administration of anti-estrogens such as tamoxifen can reduce the blood levels and thus the effectiveness of letrozole. Likewise, the intake of estrogens (including those for topical therapy in the form of creams or gels) during therapy with letrozole does not make sense.

The active substance letrozole is broken down by the CYP450 enzyme system in the liver. These enzymes also break down numerous other active substances. Although there are as yet no studies on the interactions between letrozole and such active ingredients, these are possible and should be considered when taking other drugs during therapy with letrozole. This applies in particular to active substances with a narrow therapeutic range, i.e. those which quickly become toxic if the effective dose is exceeded. This applies, for example, to phenytoin (for epilepsy and seizures) and clopidogrel (anti-coagulants).

Since the active ingredient can cause tiredness and dizziness, no vehicles should be driven or heavy machinery should be used if these side effects occur.

The use of letrozole can cause harm to the child during pregnancy and breastfeeding.

How to get medicines with letrozole

The active ingredient letrozole can be purchased from a pharmacy with a doctor's prescription. It requires a prescription in every dosage and pack size.

How long has letrozole been known?

In 1970, the pharmaceutical company Ciba-Geigy (now Novartis) began looking for an inhibitor of the key enzyme aromatase - the enzyme the body needs to produce estrogen. The first generation of aromatase inhibitors was approved in 1981 (aminoglutethimide), followed by the second generation with the active ingredient fadrozole. In 1996, the third-generation aromatase inhibitor letrozole finally came onto the market in Europe. A year later, the active ingredient was approved in the USA. The patent protection has now expired and there are also numerous generics with the active ingredient letrozole on the German pharmaceutical market.

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