Eulexin |
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Eulexin capsules have been approved for the treatment of locally confined Stage B2-C carcinoma of the prostate in combination with LHRH agonists and radiation therapy. Eulexin is currently marketed in the United States for the treatment of advanced (Stage D2) prostate cancer in combination with LHRH agonists.
Eulexin generic (generic - what is it?)
| Dosage |
Packing |
Price |
Add to basket |
| 250 mg |
30 tabs |
USD 56.00 |
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| 250 mg |
60 tabs |
USD 99.00 |
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| 250 mg |
90 tabs |
USD 129.00 |
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Medications and Prescriptions
Generic name: flutamide
Product Brand Name: Eulexin
Product Manufacturer: Manufactured in India
Eulexin (flutamide)
Company: Schering-Plough
Approval Status: Approved June 1996
Treatment for: prostate cancer
General Information
Eulexin capsules have been approved for the treatment of locally confined Stage B2-C carcinoma of the prostate in combination with LHRH agonists and radiation therapy. Eulexin is currently marketed in the United States for the treatment of advanced (Stage D2) prostate cancer in combination with LHRH agonists.
Recommended dosage is two Eulexin capsules three times a day.
Clinical Results
The application was based on a study conducted by the Radiation Therapy Oncology Group (RTOG). In the multicenter controlled clinical trial; Eulexin in combination with an LHRH agonist, was administered prior to and during radiation therapy to subjects with prostate cancer at Stage B2 (with ulky primary tumors confined to prostate) and at Stage C (extending beyond the prostate capsule), with or without pelvic noderostate cancer the opportunity to delay the onset of disease recurrence beyond that shown for radiation alone. The RTOG study also showed a statistical trend toward a reduction in the incidence of distant metastases for subjects in the Eulexin plus LHRH agonist arm.
Side Effects
In the RTOG study, treatment with Eulexin and the LHRH agonist did not add substantially to the side effects reported for radiation treatment alone.
Mechanism of Action
Eulexin is one of a class of drugs known as anti-androgens, which act by directly blocking the cancer-promoting activities of androgens, or male sex hormones, of which the principal one is testosterone. Control of metastatic prostate cancer is based on androgen deprivation. Combining Eulexin with an LHRH agonist is intended to achieve maximum androgen blockade, thereby inhibiting cancer growth.
Additional information
EULEXIN Capsules contain flutamide, an acetanilid, nonsteroidal, orally active anti-androgen having the chemical name, 2-methyl-N-[4-nitro-3 (trifluoromethyl) phenyl] propanamide.
Each capsule contains 125 mg flutamide. The compound is a buff to yellow powder with a molecular weight of 276.2 and the following structual formula:
The inactive ingredients for EULEXIN Capsules include: corn starch, lactose, magnesium stearate, povidone, and sodium lauryl sulfate. Gelatin capsule shells may contain methylparaben, propylparaben, butylparaben, and the following dye systems: FD&C Blue 1, FD&C Yellow 6, and either FD&C Red 3 or FD&C Red 40 plus D&C Yellow 10, with titanium dioxide and other inactive ingredients.
Indications & Dosage
INDICATIONS
EULEXIN Capsules are indicated for use in combination with LHRH agonists for the management of locally confined Stage B2-C and Stage D2 metastatic carcinoma of the prostate.
Stage B2-C Prostatic Carcinoma
Treatment with EULEXIN Capsules and the LHRH agonist should start 8 weeks prior to initiating radiation therapy and continue during radiation therapy.
Stage D2 Metastatic Carcinoma
To achieve benefit from treatment, EULEXIN Capsules should be initiated with the LHRH agonist and continued until progression.
DOSAGE AND ADMINISTRATION
The recommended dosage is 2 capsules 3 times a day at 8-hour intervals for a total daily dose of 750 mg.
HOW SUPPLIED
EULEXIN Capsules, 125 mg, are available as opaque, two- toned brown capsules, imprinted with "Schering 525†. They are supplied as follows:
NDC 0085-0525-05 - Bottles of 500
NDC 0085-0525-03 - Unit Dose packages of 100 (10 x 10†s)
NDC 0085-0525-06 - Bottles of 180
Store between 2o and 30o C (36o and 86o F). Protect the Unit Dose packages from excessive moisture.
Eulexin Side Effects & Drug Interactions
SIDE EFFECTS
Hot flashes, diarrhea, nausea, loss of appetite, swelling or tenderness of the breasts (gynocomastia), decreased sexual desire or ability (impotence), and decreased fertility may occur. If any of these effects persist or worsen, contact your doctor promptly. Tell your doctor immediately if you have any of these unlikely but serious side effects: rash, drowsiness, weakness, unusual fatigue, swelling of the body (edema), mental/mood changes, easy bleeding or bruising, persistent sore throat, fever, bluish skin. Tell your doctor immediately if you have any of these very unlikely but serious side effects: yellowing eyes or skin, dark urine, fever, stomach pain, lumps in your breasts, a sunburn-like effect (sun sensitivity). An allergic reaction to this drug is unlikely, but seek immediate medical attention if it occurs. Symptoms of an allergic reaction include: rash, itching, swelling, dizziness, trouble breathing. If you notice other effects not listed above, contact your doctor or pharmacist.
DRUG INTERACTIONS
Increases in prothrombin time have been noted in patients receiving long- term warfarin therapy after flutamide was initiated. Therefore, close monitoring of prothrombin time is recommended and adjustment of the anticoagulant dose may be necessary when EULEXIN Capsules are administered concomitantly with warfarin.
WARNINGS
Gynecomastia occurred in 9% of patients receiving flutamide together with medical castration.
Flutamide may cause fetal harm when administered to a pregnant woman. There was decreased 24-hour survival in the offspring of rats treated with flutamide at doses of 30, 100, or 200 mg/kg/day (approximately 3, 9, and 19 times the human dose) during pregnancy. A slight increase in minor variations in the development of the stemebrae and vertebrae was seen in fetuses of rats at the two higher doses. Feminization of the males also occurred at the two higher dose levels. There was a decreased survival rate in the offspring of rabbits receiving the highest dose (15 mg/kg/day; equal to 1.4 times the human dose).
Preclinical data from rats, cats, dogs, and monkeys, as well as clinical data in men, demonstrate that one metabolite of flutamide is 4-nitro-3-fluoromethylaniline. Several toxicities consistent with aniline exposure including methemoglobinemia, hemolytic anemia, and cholestatic jaundice have been observed in animals and humans after flutamide administration. Methemoglobin levels should be monitored in patients susceptible to aniline toxicity (e.g. persons with glucose-6-phosphate dehydrogenase deficiency or hemoglobin M disease as well as patients who smoke).
Serious cardiac lesions were observed in 2/10 beagle dogs receiving 25 mg/kg/day for 78 weeks and 3/16 receiving 40 mg/kg/day for 2-4 years. The lesions, indicative of chronic injury and repair processes, included chronic myxomatous degeneration, intra- atrial fibrosis, myocardial acidophilic degeneration, vasculitis, and perivasculitis. The doses at which these lesions occurred were associated with 2-hydroxyflutamide levels that were 1 to 12-fold greater than those observed in humans at therapeutic levels.
Hepatic Injury
Since transaminase abnormalities, cholestatic jaundice, hepatic necrosis, and hepatic encephalopathy have been reported with the use of flutamide, periodic liver function tests should be considered. (See ADVERSE REACTIONS section.) Appropriate laboratory testing should be done at the first symptom/ sign of liver dysfunction (eg, pruritus, dark urine, persistent anorexia, jaundice, right upper quadrant tenderness, or unexplained "flu-like† symptoms). If the patient has clinically evident jaundice, in the absence of biopsy-confirmed liver metastases, EULEXIN therapy should be discontinued. In clinically asymptomatic patients, if transaminases increase over 2-3 times the upper limit of normal, treatment should be discontinued. The hepatic injury is usually reversible after discontinuation of therapy, and in some patients, after dosage reduction. However, there have been reports of death following severe hepatic injury associated with use of flutamide.
PRECAUTIONS
General:
In clinical trials, gynecomastia occurred in 9% of patients receiving flutamide together with medical castration.
Information for Patients
See PATIENT INFORMAION section.
Laboratory Tests
Regular assessment of serum Prostate Specific Antigen (PSA) may be helpful in monitoring the patient's response. If PSA levels rise significantly and consistently during EULEXIN therapy the patient should be evaluated for clinical progression. For patients who have objective progression of disease together with an elevated P.A. a treatment- free period of antiandrogen while continuing the LHRH analogue may be considered.
Drug Interactions
See DRUG INTERACTIONS section.
Carcinogenesis, Mutagenesis, Impairment of Fertility
In a 1-year dietary study in male rats, interstitial cell adenomas of the testes were present in 49% to 75% of all treated rats (daily oral doses of 10, 30, and 50 mg/kg/day were administered). These produce plasma Cmax values that are 1, 2-3, and 4-fold, respectively, those associated with therapeutic doses in humans. In male rats similarly dosed for 1 year, tumors were still present after 1 year of a drug-free period, but the incidences were 43% to 47%. In a 2-year carcinogenicity study in male rats, daily administration of flutamide at these same doses produced testicular interstitial cell adenomas in 91% to 95% of all treated rats as opposed to 11% of untreated control rats. Mammary adenomas, adenocarcinomas, and fibroadenomas were increased in treated male rats at exposure levels that were 1- to 4- fold those observed during therapeutic dosing in humans. There are likewise reports of malignant breast neoplasms in men treated with EULEXIN Capsules (see ADVERSE REACTIONS section).
Flutamide did not demonstrate DNA modifying activity in the Ames Salmonella/ microsome Mutagenesis Assay. Dominant lethal tests in rats were negative.
Reduced sperm counts were observed during a 6-week study of flutamide monotherapy in normal human volunteers.
Flutamide did not affect estrous cycles or interfere with the mating behavior of male and female rats when the drug was administered at 25 and 75 mg/kg/day prior to mating. Males treated with 150 mg/kg/day (30 times the minimum effective antiandrogenic dose) failed to mate; mating behavior returned to normal after dosing was stopped. Conception rates were decreased in all dosing groups. Suppression of spermatogenesis was observed in rats dosed for 52 weeks at approximately 3, 8, or 17 times the human dose and in dogs dosed for 78 weeks at 1.4, 2.3, and 3.7 times the human dose.
Animal Toxicology:
Serious cardiac lesions were observed in 2/10 beagle dogs receiving 25 mg/kg/day for 78 weeks and 3/16 receiving 40 mg/kg/day for 2-4 years. These lesions, indicative of chronic injury and repair processes, included chronic myxomatous degeneration, intraatrial fibrosis, myocardial acidophilic degeneration, vasculitis, and perivasculitis. The doses at which these lesions occurred were associated with 2-hydroxyflutamide levels that were 1- to 12-fold greater than those observed in humans at therapeutic levels.
Pregnancy: Pregnancy Category D. There was decreased 24-hour survival in the offspring of pregnant rats treated with flutamide at doses of 30, 100, or 200 mg/kg/day (approximately 3, 9, and 19 times the human dose). A slight increase in minor variations in the development of the sternebrae and vertebrae was seen in fetuses of rats treated with two higher doses. Feminization of the male rats also occurred at the two higher dose levels. There was a decreased survival rate in the offspring of rabbits receiving the highest dose (15 mg/kg/day, equal to 1.4 times the human dose).
OVERDOSE
In animal studies with flutamide alone, signs of overdose included hypoactivity, piloerection, slow respiration, ataxia, and/or lacrimation, anorexia, tranquilization, emesis, and methemoglobinemia.
Clinical trials have been conducted with flutamide in doses up to1500mg per day for periods up to 36 weeks with no serious adverse effects reported. Those adverse reactions reported included gynecomastia, breast tenderness, and some increases in SGOT. The single dose of flutamide ordinarily associated with symptoms of overdose or considered to be life-threatening has not been established.
Flutamide is highly protein bound and is not cleared by hemodialysis. As in management of overdosage with any drug, it should be borne in mind that multiple agents may have been taken. If vomiting does not occur spontaneously, it should be induced if the patient is alert. General supportive care, including frequent monitoring of the vital signs and close observation of the patient, is indicated.
CONTRAINDICATIONS
EULEXIN Capsules are contraindicated in patients who are hypersensitive to flutamide or any component of this preparation.
EULEXIN Capsules are contraindicated in patients with severe hepatic impairment (baseline hepatic enzymes should be evaluated prior to treatment.
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Drug category:Anti-cancer drugs
 Eulexin
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