What is Lysodren?
Lysodren is a medicine that contains the active substance mitotane. It is available as white round tablets (500 mg).
What is Lysodren used for?
Lysodren is indicated in the symptomatic treatment of adrenal cortical carcinoma (tumor of the peripheral part of the adrenal gland) in the advanced phase, when the tumor is not resectable (it cannot be removed by surgery) or is metastatic (it has spread to other parts of the body ) or relapse (it has recurred after a first treatment).
Because the number of patients with adrenocortical carcinoma is low, the disease is considered "rare" and Lysodren was designated an "orphan medicine" (a medicine used in rare diseases) on 12 June 2002.
The medicine can only be obtained with a prescription .
How is Lysodren used?
Treatment with Lysodren should be started and continued under the supervision of a specialist with adequate experience. The recommended starting dose in adults is 2-3 g per day, divided into two or three doses, preferably taken during meals based on fatty foods. In patients in whom the symptoms of Cushing's syndrome (a set of symptoms of adrenal gland cancer caused by elevated hormone levels) must be urgently controlled, the initial dose may be 4-6 g per day. The dose must be increased gradually until reaching an "optimal" dose that allows the best results to be obtained without causing unacceptable side effects. It is necessary to check often the concentration of the active ingredient in the blood, considering that the final dose should reach blood levels between 14 and 20 mg per liter. This is usually achieved within three to five months. Levels above 20 mg / l can cause serious side effects without increasing the effectiveness of the medicine.
The dose may be reduced or treatment may be interrupted if side effects occur. Treatment should be continued as long as benefits are found. If there is no improvement in symptoms after three months of treatment with the optimal dose, treatment should be discontinued.
There is little information on the use of Lysodren in children, but a daily starting dose of 1.5-3.5 g per square meter of body surface is recommended (calculated based on the height and weight of the child).
The use of Lysodren is not recommended in patients who have severe liver or kidney problems and the drug should be used with caution in subjects with mild to moderate liver or kidney problems. It should also be used with caution in elderly patients, frequently monitoring their blood levels.
Patients taking Lysodren should receive the "Lysodren Patient Card", which they must carry with them in an emergency, to inform health professionals (such as doctors and nurses) that they are taking the drug.
How does Lysodren work?
The cortex of the adrenal gland produces steroid hormones. When a tumor develops in this area, the levels of these hormones can increase causing the symptoms of the disease. The active ingredient contained in Lysodren, mitotane, is a drug that is believed to work by preventing the cells of the adrenal gland from performing its functions properly, damaging the mitochondria (energy-producing components) and thereby reducing the production of some steroid hormones. It can also alter the decomposition of these hormones. All these effects reduce the concentration of hormones in the body, improving the symptoms of the disease.
What studies have been performed on Lysodren?
Since the active substance in Lysodren, the mitotane, is a well-known drug used in Europe for the treatment of adrenocortical carcinoma since 1959, the company presented information from the published literature in support of its application for authorization for Lysodren.
In particular, he presented the results of 220 studies published since 1990 on the use of the drug in unresectable metastatic adrenal cortical carcinoma. The studies were conducted on 500 adult and child patients, treated with mitotane for different periods of time, alone (alone) or in combination with other anticancer drugs. The main parameters of effectiveness in these studies included survival time, reduction in tumor size and time spent without symptoms of the disease.
What benefit has Lysodren shown during the studies?
In general, studies have shown that Lysodren can be beneficial in patients with advanced adrenocortical carcinoma, prolonging survival time (in some cases for more than five years) and reducing or stabilizing tumor size in 20-30% of patients. Treatment with Lysodren also reduced the symptoms of the disease, particularly in patients whose cancer produced elevated hormone levels. However, insufficient data are available to support its use as an adjunctive therapy compared to other anticancer drugs. There are few information on the use of mitotane in children, but in general pediatric patients treated with the drug remained free of the disease, on average, for seven months.
What are the risks associated with Lysodren?
The most common side effects with Lysodren (seen in more than 1 patient in 10) are increased levels of liver enzymes, cholesterol and triglycerides (one type of fat), leukopenia (low white blood cell count), prolonged bleeding time, ataxia (difficulty in coordinating movements), paresthesia (sensitivity disorders such as pins and needles), dizziness (dizziness), drowsiness, mucositis (inflammation of the mucous membranes, such as that of the mouth), vomiting, diarrhea, nausea, epigastralgia (pain to the stomach), rash, myasthenia (muscle weakness), adrenal insufficiency (reduced activity of the adrenal gland), anorexia (loss of appetite), asthenia (weakness), gynecomastia (excessive development of the udder in humans) and confusion. For the full list of all side effects reported with Lysodren, see the Package Leaflet.
Lysodren should not be used in patients who may be hypersensitive (allergic) to mitotane or any of the other ingredients. It should not be used during lactation or by patients taking spironolactone (a diuretic medicine).
Why has Lysodren been approved?
The Committee for Medicinal Products for Human Use (CHMP) decided that Lysodren's benefits are greater than its risks for the treatment of advanced adrenocortical carcinoma, but noted that the effect of Lysodren is not demonstrated in adrenal cortical carcinoma that does not produce high levels. of steroid hormones. The Committee recommended that Lysodren be given marketing authorization.
More information on Lysodren
On 28 April 2004, the European Commission issued a marketing authorization valid for Lysodren, valid throughout the European Union, to Laboratoire HRA Pharma. The marketing authorization was renewed on 28 April 2009.
For a summary of the opinion of the Committee for Orphan Medicinal Products on Lysodren, click here.
The full EPAR for Lysodren can be found here.
Last update of this summary: 04-2009
