Eulexin

Eulexin is a non-steroidal antiandrogenic drug with antitumor activity. It competitively blocks the interaction of androgens with their cellular receptors.

Pharmachologic effect

The mechanism of action is associated with the inhibition of androgen uptake and/or inhibition of androgen binding in the nuclei of target tissue cells. Its ability to inhibit the effects of testosterone at the cellular level is in addition to the medication “castration” caused by gonadotropin-releasing hormone (GnRH) agonists.

Target organs of the pharmacological action of flutamide (the main component of Eulexin) are the prostate gland and seminal vesicles. Eulexin does not have estrogenic, antiestrogenic, progestogen and antiestrogenic properties.

Indications for use

Treatment of metastatic prostate cancer when testosterone suppression is indicated:

• at the beginning of treatment in combination with GnRH agonists;
• as an additional treatment for patients already receiving agonist therapy;
• in patients with surgical castration;
• with intolerance or ineffectiveness of other types of hormone therapy.

Dosage and administration

Eulexin is prescribed 1 tablet 3 times/day every 8 hours. The duration of treatment is determined by the attending physician. As part of clinical trials, therapy was carried out for 4.5 years. If a positive effect is achieved, the drug is used until signs of tumor progression appear.

In the case of combined therapy with GnRH agonists, both drugs can be prescribed at the same time, or Flutamide is started 3 days before the first administration of GnRH agonists. Do not withdraw or arrest treatment without consulting your physician.

Flutamide should be started 8 weeks before the beginning of external radiation therapy and continued throughout the course of radiation therapy.

If you miss a dose, continue treatment as usual. Do not take extra tablets.

Contraindications

• Hypersensitivity to flutamide or to any other drug component;
• Severe hepatic failure;
• Children’s age (safety and efficacy not detected).

With caution: in patients with reduced liver function, with a tendency to thrombosis and cardiovascular diseases, as well as in conditions predisposing to aniline intoxication (one of the metabolites of flutamide is a methylaniline derivative): glucose-b-phosphate dehydrogenase deficiency, smoking, hemoglobinopathy (M-hemoglobin).

Side effects

• Endocrine system: often (10% or more) – gynecomastia and/or pain in the area of the mammary glands, sometimes accompanied by galactorrhea (these phenomena disappear when you stop taking it or after a dose reduction); rarely (less than 1%) – decreased libido; with prolonged treatment, suppression of spermatogenesis was noted.
• Digestive system: sometimes (from 1% to 10%) – diarrhea, nausea, vomiting, increased appetite, transient impaired liver function, hepatitis; rarely – anorexia, heartburn, constipation, dyspepsia, jaundice (including cholestatic), liver necrosis, hepatic encephalopathy, increased transaminase activity.
• Central nervous system: sometimes – insomnia, fatigue; rarely – headache, dizziness, weakness, visual impairment, anxiety, depression.
• Hemopoietic system: rarely – thrombocytopenia; in some cases, hemolytic anemia, macrocytic anemia, methemoglobinemia.
• Dermatological reactions: rarely – subcutaneous hemorrhage, itching; in some cases, photosensitization (including erythema, ulceration of the skin, epidermal necrolysis).
• Other: rarely – increased blood pressure, thirst, chest pain, swelling (fingers, feet, legs), lupus-like syndrome, a change in the color of urine from amber to yellow-green.

When used in combination with GnRH agonists:

• endocrine system: often – hot flashes, decreased libido, impotence; sometimes gynecomastia.
• digestive system: often – diarrhea, nausea, vomiting; sometimes – lack of appetite; rarely – hepatitis, cholestatic jaundice, liver failure, liver necrosis, hepatic encephalopathy.
• hemopoietic system: sometimes – anemia, leukopenia, thrombocytopenia.
• central nervous system and peripheral nervous system: sometimes – symptoms of neuromuscular disorders (numbness, tingling, pain or muscle weakness in the arms, hands, feet, legs), drowsiness, depression, confusion, anxiety, neurosis.
• cardiovascular system: sometimes – arterial hypertension.From the respiratory system: rarely – respiratory failure.
• dermatological reactions: rarely – photosensitivity.
• other: sometimes – swelling, difficulty urinating; rarely – methemoglobinemia.

Overdose

Symptoms: aggravation of side effects.

In clinical trials, flutamide was administered at doses up to 1,500 mg/day for up to 36 weeks, with no severe side effects. Adverse reactions such as gynecomastia, breast tenderness, and a slight increase in the ACT were most commonly reported. It has not been established which single doses of flutamide can cause overdose symptoms or endanger human life.

Treatment: In the case of an overdose, dialysis is ineffective due to the high degree of binding of flutamide to blood plasma proteins. In case of an overdose, the patient could take several drugs. Treatment should be symptomatic and supportive. The patient should be constantly monitoring vital body functions.

Interaction with other drugs

Drug interaction between Eulexin and leuprolide does not occur. In patients receiving warfarin for a long time, an increase in prothrombin time is observed after the initiation of monotherapy with flutamide. Therefore, the combined use of Eulexin and warfarin requires careful monitoring of prothrombin time and, possibly, dose adjustment of the anticoagulant.