Frugyl (Tablets) Instructions for Use

Marketing Authorization Holder

Rusan Pharma, Ltd. (India)

ATC Code

L02BB01 (Flutamide)

Active Substance

Flutamide (Rec.INN registered by WHO)

Dosage Form

Frugyl

Tablets 250 mg: 20 pcs

Dosage Form, Packaging, and Composition

10 pcs. – blisters (2) – cardboard packs.

Clinical-Pharmacological Group

Antiandrogenic drug with antitumor activity

Pharmacotherapeutic Group

Antineoplastic agent, antiandrogen

Pharmacological Action

It is a non-steroidal antiandrogenic agent. By blocking androgen receptors of target cells, it prevents the development of biological effects of endogenous androgens, which leads to disruption of tumor cell replication. It helps to reduce the size and density of the prostate gland and prevents the development of the metastatic process.

It does not possess estrogenic, antiestrogenic, progestogenic, or antiprogestogenic activity.

Pharmacokinetics

After oral administration, it is rapidly and completely absorbed from the gastrointestinal tract. Plasma protein binding is 94-96%. After repeated oral administration at a dose of 250 mg 3 times/day, the equilibrium concentration of flutamide and its active metabolite in plasma was achieved after the 4th dose.

It is metabolized to form an active metabolite, hydroxyflutamide, and 5 other metabolites. It is excreted mainly in the urine; 4.2% of the dose is excreted in the feces within 72 hours. The T_1/2 of hydroxyflutamide is 6 hours.

In elderly patients, the T_1/2 is 8 hours after a single administration and 9.6 hours at equilibrium concentration.

Indications

Treatment of metastatic prostate cancer when suppression of testosterone action is indicated: at the beginning of treatment in combination with GnRH agonists; as an additional treatment for patients already receiving therapy with GnRH agonists; in patients with surgical castration; treatment of patients for whom other types of hormone therapy have been ineffective or who are intolerant to such treatment.

ICD codes

Dosage Regimen

Administer orally at a dose of 250 mg three times daily.

Maintain an approximately 8-hour interval between doses to ensure consistent therapeutic levels.

Swallow the tablet whole with a sufficient amount of water; it can be taken with or without food.

The total daily dosage is 750 mg.

This regimen is indicated for the treatment of metastatic prostate carcinoma.

Initiate therapy in combination with a GnRH agonist to suppress the initial testosterone flare.

Use as an adjunctive treatment for patients already receiving GnRH agonist therapy.

Continue treatment for as long as a clinical benefit is observed and the patient tolerates the therapy.

Do not adjust the dosage based solely on patient age.

Perform regular liver function tests before and during treatment due to the risk of hepatotoxicity.

Discontinue treatment immediately if clinical jaundice develops or if transaminase levels exceed 2-3 times the upper limit of normal.

Adverse Reactions

From the reproductive system: gynecomastia and/or breast tenderness, galactorrhea, decreased libido, reduced sperm production, increased plasma testosterone concentration (at the initial stage of therapy).

From the digestive system: dyspepsia, nausea, vomiting, diarrhea, constipation, heartburn.

From the liver and biliary tract: transient liver function disorders, increased activity of liver transaminases, jaundice, hepatitis.

From the hematopoietic system: lymphedema.

From the nervous system: dizziness, headache, visual disturbances.

From the psyche: insomnia, anxiety, depression.

From the respiratory system: interstitial pneumonitis, dyspnea, cough.

From the skin and subcutaneous tissues: itching, ecchymoses, photosensitivity, change in hair structure.

From metabolism: increased appetite, anorexia.

Infectious diseases: herpes zoster.

Benign, malignant and unspecified neoplasms (including cysts and polyps): breast neoplasms in men.

From the cardiovascular system: QT interval prolongation, hot flashes, increased blood pressure.

From the immune system: lupus-like syndrome.

General reactions: increased fatigue, weakness, malaise, thirst, chest pain, edema.

Contraindications

Hypersensitivity to flutamide; severe hepatic insufficiency; children and adolescents under 18 years of age (efficacy and safety have not been established).

With caution

In patients with impaired liver function, with renal insufficiency, with a tendency to thrombosis and with cardiovascular diseases, as well as in conditions predisposing to aniline intoxication (one of the metabolites of flutamide is a methylaniline derivative): glucose-6-phosphate dehydrogenase deficiency, smoking, hemoglobinopathy.

Use in Pregnancy and Lactation

Not applicable.

Use in Hepatic Impairment

Contraindicated in severe hepatic insufficiency. Should be used with caution in patients with impaired liver function.

Use in Renal Impairment

Should be used with caution in patients with renal insufficiency.

Pediatric Use

Contraindicated in children and adolescents under 18 years of age (efficacy and safety have not been established).

Special Precautions

When flutamide is used concomitantly with GnRH agonists, blood glucose and/or glycated hemoglobin levels and bone mineral density should be monitored.

In patients with impaired liver function, the use of flutamide for a long period is possible only after careful analysis of the risk/benefit ratio. Liver function should be assessed before starting treatment with flutamide. Treatment with flutamide should not be started if plasma liver transaminase activity is increased more than 2-3 times. Flutamide therapy should be carried out under the control of blood liver transaminase activity once a month for the first 4 months of therapy and periodically thereafter, or upon development of the first signs/symptoms of liver dysfunction (itching, dark urine, persistent loss of appetite, jaundice, tenderness in the right upper quadrant, or flu-like symptoms unexplained by other causes). Flutamide therapy should be discontinued in the presence of laboratory signs of liver damage or clinical jaundice in the absence of biopsy-confirmed liver metastases, or with more than a 2-3-fold increase in plasma liver transaminase activity without pathological signs.

During treatment, an increase in plasma concentrations of testosterone and estradiol is possible, which can cause fluid retention in the body. In severe cases, this may lead to an increased risk of angina and heart failure. Flutamide may exacerbate peripheral edema or ankle swelling in patients prone to these conditions. An increase in plasma estradiol concentration may lead to an increased frequency of thromboembolic complications.

Antiandrogenic therapy may contribute to QT interval prolongation. Before using flutamide in patients with a history of QT interval prolongation or with factors that may lead to QT interval prolongation, as well as in patients taking concomitant medications that may cause QT interval prolongation, the physician should assess the benefit/risk ratio, including the possible development of torsades de pointes arrhythmia in such patients.

Long-term therapy in patients without medical or surgical castration requires regular monitoring of spermogram.

Flutamide is indicated for use only in men. Reliable methods of contraception must be used during treatment with flutamide.

Drug Interactions

No interactions between flutamide and leuprorelin have been observed; however, with combination therapy of flutamide and GnRH agonists, the possible side effects of each drug should be taken into account.

In patients receiving oral anticoagulant therapy, an increase in prothrombin time was noted after starting treatment with flutamide. With the use of this combination, careful monitoring of prothrombin time is recommended; dose adjustment of the anticoagulant may be required.

Cases of increased plasma theophylline concentration have been reported with concomitant use with flutamide.

Concomitant use of another potentially hepatotoxic drug is possible only after a thorough assessment of the benefit-risk ratio.

Given the known possible hepatotoxicity and nephrotoxicity of flutamide, excessive alcohol consumption should be avoided.

Since antiandrogenic therapy may contribute to QT interval prolongation, the concomitant use of flutamide and drugs that promote QT interval prolongation, or drugs that may lead to the development of torsades de pointes arrhythmia, should be carefully evaluated, including class IA antiarrhythmic drugs (e.g., quinidine, disopyramide) or class III (e.g., amiodarone, sotalol, dofetilide, ibutilide), methadone, moxifloxacin, antipsychotics.

Storage Conditions

Store at 2°C (36°F) to 25°C (77°F). Keep in original packaging, protected from light. Keep out of reach of children.

Dispensing Status

Rx Only

Important Safety Information

This information is for educational purposes only and does not replace professional medical advice. Always consult your doctor before use. Dosage and side effects may vary. Use only as prescribed.