Flutapharm® femina

INSTRUCTIONS FOR MEDICAL USE OF THE MEDICINAL PRODUCT FLUTAFARM® FEMINA (FLUTAFARM® FEMINA)

Composition:

Active ingredient: flutamide;

1 tablet contains flutamide calculated as 100% substance – 125 mg (0.125 g);

Excipients: potato starch, lactose monohydrate, colloidal anhydrous silicon dioxide, calcium stearate.

Dosage form. Tablets.

Main physicochemical properties: light-yellow tablets, flat surface, with a score line on one side and bevelled edges.

Pharmacotherapeutic group. Hormone antagonists and related agents. Antiandrogen agents. ATC code L02BB01.

Pharmacological properties.

Pharmacodynamics.

Flutapharm**®** Femina is a non-steroidal agent with antiandrogenic activity.

In women with hyperandrogenic conditions associated with infertility and disturbances of the ovulatory-menstrual cycle (e.g., polycystic ovary syndrome), Flutapharm**®** Femina blocks the pathogenic effects of endogenous androgens on the ovaries and other reproductive organs, as well as on the hypothalamic-pituitary system. As a result, symptoms of hyperandrogenism (hirsutism) are reduced, menstruation is restored, folliculogenesis and the menstrual cycle improve, which may lead to the restoration of fertility potential in some patients.

Pharmacokinetics.

Flutamide is well absorbed from the gastrointestinal tract. Maximum blood concentration is reached within 2 hours after oral administration. It is rapidly metabolized, forming the active metabolite 2-hydroxyflutamide and other substances. The elimination half-life of the active metabolite is 5–6 hours. Elimination is primarily via urine. Within 2 days, 91% of the administered dose is excreted from the body; within 3 days, 98%.

Clinical characteristics.

Indications.

Treatment of women with functional hyperandrogenism associated with ovarian-menstrual cycle disorders, hirsutism, polycystic ovary syndrome, and infertility.

Contraindications.

Hypersensitivity to flutamide or to any of the excipients. Organic hyperandrogenism (ovarian or adrenal cortex tumors). Severe hepatic impairment (baseline liver enzyme levels should be assessed prior to initiating treatment).

Children.

Interaction with other medicinal products and other forms of interaction.

No interaction between flutamide and leuprolide has been observed. When flutamide and GnRH agonists are used concomitantly, the potential adverse effects of both agents should be considered.

An increase in prothrombin time has been reported in patients receiving long-term warfarin therapy following administration of flutamide. Therefore, the optimal dose of anticoagulant should be carefully adjusted.

Concomitant use of flutamide and theophylline may lead to increased plasma concentrations of theophylline.

Concomitant use of flutamide and potentially hepatotoxic medicinal products should be avoided.

There is a possibility of interaction when flutamide is used concomitantly with paracetamol and opioid analgesics.

Flutamide may slow down the metabolism of corticosteroids.

Alcohol consumption should be avoided during treatment.

Concomitant administration of flutamide with medicinal products that prolong the QT interval or those capable of inducing torsades de pointes/ventricular fibrillation, such as Class IA (e.g., quinidine, disopyramide) or Class III (e.g., amiodarone, sotalol, dofetilide, ibutilide) antiarrhythmic agents, methadone, moxifloxacin, neuroleptics, should be carefully evaluated.

Special precautions for use.

Patients should be under constant medical supervision. Particular attention should be paid to the effect of flutamide on liver function.

Flutamide may be used for long-term therapy in patients with liver function disorders only after careful assessment of the expected benefits and potential risks.

Liver function should be checked before starting treatment. Treatment with the drug should not be initiated in patients whose serum transaminase levels exceed the upper limit of normal by 2–3 times.

Appropriate laboratory testing should be performed monthly during the first 4 months of treatment and periodically thereafter, as well as at the first signs or symptoms of liver dysfunction (pruritus, dark urine, persistent loss of appetite, jaundice, mild pain in the right upper quadrant of the abdomen, or general weakness).

Liver function abnormalities are usually reversible upon discontinuation of flutamide therapy. However, there have been reports of fatal cases due to severe liver damage caused by flutamide.

Flutamide is primarily excreted by the kidneys; therefore, dose adjustment may be required in patients with renal impairment.

The physician should assess the benefit-risk ratio, including the likelihood of developing fluttering/palpitations, before initiating flutamide treatment in patients with a history of or risk factors for QT prolongation, as well as in patients receiving concomitant medications that may prolong the QT interval.

Since flutamide treatment increases plasma levels of testosterone and estradiol, fluid retention in body tissues may occur. Therefore, flutamide should be prescribed with caution to patients with heart disease. In addition, increased estradiol levels may increase the risk of thromboembolism.

Patients with latent or overt glucose-6-phosphate dehydrogenase deficiency may develop methemoglobinemia. In case of cyanosis or methemoglobinemia, the possibility of drug overdose should be considered.

Flutaferm**®** Femina contains lactose; therefore, patients with rare hereditary forms of galactose intolerance, lactase deficiency, or glucose-galactose malabsorption should not take this medication.

Alcohol consumption should be avoided during treatment.

Use during pregnancy or breastfeeding.

When prescribing the drug to women, special attention should be paid to preventing pregnancy using non-hormonal, particularly barrier, contraceptive methods. If a pregnancy test is positive, the drug must be discontinued immediately. Sexual intercourse with the aim of achieving pregnancy may be resumed no earlier than 48 hours after the last dose of Flutaferm**®** Femina.

Ability to affect reaction speed when driving or operating machinery.

The drug usually does not affect reaction speed when driving or operating machinery. However, in individual cases, increased fatigue, dizziness, or partial impairment of consciousness may occur. In such cases, patients should refrain from driving or operating machinery.

Dosage and Administration

For women with hyperandrogenic conditions, Flutafarm® Femina is administered orally, 1 tablet (125 mg) three times daily for 3–6 months. The tablets should be taken during or after meals. Concurrent use of non-hormonal contraceptive methods, particularly barrier methods, is mandatory.

Children

The drug is not intended for use in pediatric patients.

Overdose

In animal experiments, flutamide caused hypoactivity, piloereiction, respiratory depression, ataxia and/or lacrimation, anorexia, sedation, vomiting, and methemoglobinemia.

Clinical data indicate that administration of flutamide at daily doses up to 1500 mg for 36 weeks does not cause serious adverse effects. Occasionally, gynecomastia and transient changes in liver transaminase levels may occur. A single dose of flutamide of up to 5 g does not produce overdose symptoms and is not life-threatening.

Symptoms of flutamide overdose that are life-threatening in humans have not been reported.

Due to the high degree of plasma protein binding of flutamide, it cannot be effectively removed by dialysis. As with management of overdose of any medicinal product, the possibility of concomitant intake of multiple drugs should be considered. General supportive measures to monitor and maintain vital functions are recommended. Gastric lavage may be necessary.

Adverse reactions.

The adverse reactions described below are characteristic of the active substance flutamide.

Infections and infestations.

Herpes zoster.

Blood and lymphatic system disorders.

Lymphedema, anemia, leukopenia, thrombocytopenia, methemoglobinemia, ecchymoses.

Metabolism and nutrition disorders.

Increased appetite, anorexia.

Psychiatric disorders.

Insomnia, depression, anxiety.

Nervous system disorders.

Dizziness, headache, somnolence.

Immune system disorders.

Lupus-like syndrome.

Eye disorders.

Blurred vision.

Cardiac disorders.

Flushing, QT prolongation, cardiovascular disorders.

Respiratory, thoracic and mediastinal disorders.

Dyspnea, cough.

Gastrointestinal disorders.

Diarrhea, nausea, vomiting, increased appetite, non-specific gastrointestinal complaints, heartburn, constipation, gastrointestinal dysfunction, stomach area pain, gastric disorders, ulcer-like pain, stomatitis.

Hepatobiliary disorders.

Hepatitis, jaundice, increased liver function test parameters.

Hepatic disorders usually resolve after discontinuation of flutamide; severe toxic hepatitis, liver necrosis, and hepatic encephalopathy (these adverse reactions are usually reversible and resolve after discontinuation of therapy). Isolated fatal outcomes associated with liver damage due to flutamide administration have been reported.

Renal and urinary disorders.

Increased blood urea and creatinine levels (the severity of this adverse effect usually does not require dose reduction or discontinuation of the drug), green discoloration of urine.

Skin and subcutaneous tissue disorders.

Itching, subcutaneous hemorrhages, photosensitivity, rash, alopecia; at the beginning of flutamide therapy, reversible changes in hair structure may occur.

Reproductive system and breast disorders.

Breast area pain, galactorrhea, decreased libido.

General disorders.

Increased fatigue, edema, weakness, anxiety, thirst, retrosternal pain, fever.

Investigations.

Transient liver function abnormalities.

Shelf life. 3 years.

Do not use the medicinal product after the expiry date stated on the packaging.

Storage conditions.

Store in the original packaging at a temperature not exceeding 25 °C.

Keep out of reach of children.

Packaging. 10 tablets in a blister. 3 blisters in a pack.

Prescription status. Prescription only.

Manufacturer. JSC "Farmak".

Manufacturer's address and place of business.

74, Kyrylivska Street, Kyiv, 04080, Ukraine.