Eulexin (flutamide)
Antiandrogen Oral Capsule
Last reviewed · Source: First Databank (FDB) drug data
Overview
Flutamide, a nonsteroidal antiandrogen, is an antineoplastic agent.
Flutamide, a toluidine derivative, is a nonsteroidal antiandrogen that is structurally and pharmacologically related to bicalutamide and nilutamide.
Flutamide is a pure antiandrogen, possessing no intrinsic hormonal activity; the antiandrogenic mechanism of action of the drug is via androgen-receptor antagonism. Flutamide inhibits the action of androgens by competitively blocking nuclear androgen receptors in target tissues such as the prostate, seminal vesicles, and adrenal cortex; blockade of androgen receptors in the hormone-sensitive tumor cells may result in growth arrest or transient tumor regression through inhibition of androgen-dependent DNA and protein synthesis. Flutamide is a selective antiandrogen with no estrogenic, antiestrogenic, progestational, antiprogestational, antigonadotropic, or adrenocortical activity in various animal models.
Flutamide is metabolized in vivo to 2-hydroxyflutamide, which appears to be principally responsible for the antiandrogenic activity; this metabolite is a potent competitive inhibitor of androgen-receptor binding, exhibiting 1.5 times the antiandrogenic potency of flutamide in animal models. The relative binding affinity of 2-hydroxyflutamide at the androgen receptor is less than that of bicalutamide but similar to that of nilutamide. In addition to blocking the binding of dihydrotestosterone (DHT) at androgen receptors, flutamide inhibits androgen uptake into target cells, and decreases the number of intraprostatic androgen receptors by secondarily (i.e., subsequent to DHT-binding blockade) preventing translocation of the androgen-receptor complex into cellular nuclei.
Metabolism of adrenal androgen precursors of testosterone (e.g., dehydroepiandrosterone (DHEA)) to inactive metabolites increases in castrated patients with prostatic cancer receiving flutamide.
Common pharmacologic therapies for prostate cancer (i.e., gonadotropin-releasing hormone (GnRH) analogs, nonsteroidal antiandrogens) when used as monotherapy initially result in increased serum testosterone concentrations, which may limit the effect of the drug. Androgen receptors in the hypothalamus are blocked by flutamide, which disrupts the inhibitory feedback of testosterone on luteinizing hormone (LH) release, resulting in a temporary increase in secretion of LH; the increase in LH stimulates an increase in the production of testosterone. As GnRH analogs have potent GnRH agonist properties, testicular steroidogenesis continues during the first few weeks after initiating therapy.
However, the combination of orchiectomy or GnRH analog therapy to suppress testicular androgen production and an antiandrogen to block response of remaining adrenal androgens provides maximal androgen blockade. Concomitant administration of antiandrogens such as nilutamide in patients initiating therapy with a GnRH analog can inhibit initial androgenic stimulation and potential exacerbation of symptoms (e.g., bone pain, urinary obstruction, liver pain, impending spinal cord compression) that may occur during the first month of GnRH analog therapy. (See Cautions in Leuprolide Acetate 10:00.)
The American Society of Health-System Pharmacists, Inc. represents that the information provided in the accompanying monograph was formulated with a reasonable standard of care, and in conformity with professional standards in the field. Readers are advised that decisions regarding use of drugs are complex medical decisions requiring the independent, informed decision of an appropriate health care professional, and that the information contained in the monograph is provided for informational purposes only. The manufacturer's labeling should be consulted for more detailed information.
The American Society of Health-System Pharmacists, Inc. does not endorse or recommend the use of any drug. The information contained in the monograph is not a substitute for medical care.
USES: This medication is used to treat men with prostate cancer. Flutamide belongs to a class of drugs known as anti-androgens (anti-testosterone). Testosterone, a natural hormone, helps prostate cancer to grow and spread.
Flutamide works by blocking the effects of testosterone, thereby slowing the growth and spread of prostate cancer.
Generic name: flutamide
Pronunciation: (FLEW-tuh-mide)
Drug class: Antiandrogen
Therapeutic class: Antineoplastics
Reference product & biosimilars
No reference, biosimilar or interchangeable associated with this drug.
Today’s intelligence on Eulexin
Indications
The following indications are listed for Eulexin:
- Prostatic Carcinoma
Also known as: Malignancy Of Prostate, Malignant Neoplasm Of Prostate, Malignant Tumor Of Prostate, Prostate Cancer.
Dosing
Because of the intended labeled use of flutamide, safety and efficacy of the drug have not been established in women or children. Flutamide is not intended for use in women and should not be used in women, particularly for nonserious or nonlife-threatening conditions.
Patients should be advised of the possibility of facial flushing during flutamide therapy and that alcohol could exacerbate this effect. Patients who experience such intolerance during therapy with the drug should avoid alcohol consumption.
Flutamide is extensively metabolized to at least 6 metabolites.
No information is available concerning use of flutamide in patients with hepatic impairment. The manufacturer states that flutamide should not be used in patients with severe hepatic impairment. Serum transaminase concentrations should be measured prior to initiation of flutamide therapy, at regular intervals during the first 4 months of treatment, and periodically thereafter in all patients receiving flutamide. (See Discontinuance of Therapy for Hepatic Toxicity, in Dosage and Administration: Dosage.)
In individuals with chronic renal insufficiency receiving a single 250-mg dose of flutamide, there was no correlation between creatinine clearance and plasma concentrations of the drug. Renal impairment did not affect peak concentrations or AUCs of the drug and principal active metabolite. In individuals with a creatinine clearance of less than 29 mL/minute, the half-life of the active metabolite is slightly prolonged. Adjustment of flutamide dosage in patients with renal impairment generally is unnecessary.
Flutamide is administered orally without regard to meals.
| Drug label | Dosing type | Instructions |
|---|---|---|
| Eulexin 125 Mg Capsule | Maintenance | Take 2 capsules (250 mg) by oral route every 8 hours. |
No dosing information is available for this tab.
Drug interactions
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Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.
Selected Agents/Mibefradil
SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.
MECHANISM OF ACTION: Mibefradil has been shown to inhibit the activity of CYP P-450-3A4 and CYP P-450-2D6 and may inhibit the metabolism of these agents.(1-2)
CLINICAL EFFECTS: Concurrent administration may result in elevated levels of these agents.(1,2) Withdrawal of mibefradil may result in decreased levels of these agents. Concurrent administration of the mibefradil with the HMG-CoA reductase inhibitors may result in elevated levels of the HMG-CoA reductase inhibitors, which may result in rhabdomyolysis.(1)
PREDISPOSING FACTORS: None determined.
PATIENT MANAGEMENT: Patients who received concurrent therapy with mibefradil and these agents should be monitored for decreased levels and effectiveness of these medications during the two weeks following the withdrawal of mibefradil. Dosage adjustments of the medications may be necessary. The manufacturer of mibefradil stated that concurrent administration of mibefradil with either lovastatin or simvastatin was contraindicated and that concurrent administration of mibefradil with either atorvastatin or cerivastatin should have generally been avoided.(1) Fluvastatin or pravastatin, which are not significantly metabolized by CYP P-450-3A4, may have been used as alternatives in patients receiving mibefradil.
DISCUSSION: Mibefradil was shown to inhibit CYP P-450-3A4 and CYP P-450-2D6 thus may inhibit the metabolism of agents metabolized at these sites. Withdrawal of mibefradil may result in decreased levels of these agents as the CYP P-450 system returns to normal. Following the discontinuation of mibefradil, seven to 14 days are required for sufficient elimination of mibefradil metabolites to minimize mibefradil effects on the CYP P-450 system. Dosage adjustments may need to be made during this period.(2) The manufacturer stated that there were seven reports of rhabdomyolysis in patients receiving concurrent therapy with simvastatin and mibefradil. Four patients were also receiving cyclosporine. Because lovastatin follows the same metabolic pathway as simvastatin, a similar interaction would be expected. Atorvastatin and cerivastatin are metabolized by CYP P-450-3A4 to active and inactive metabolites.(1)
Severe Interaction: Action is required to reduce the risk of severe adverse interaction.
Myelosuppressives; Immunomodulators/Sodium Iodide I 131
SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction.
MECHANISM OF ACTION: Sodium iodide I 131 can cause depression of the hematopoetic system. Myelosuppressives and immunomodulators also suppress the immune system.(1)
CLINICAL EFFECTS: Concurrent use of sodium iodide I 131 with agents that cause bone marrow depression, including myelosuppressives or immunomodulators, may result in an enhanced risk of hematologic disorders, including anemia, blood dyscrasias, bone marrow depression, leukopenia, and thrombocytopenia. Bone marrow depression may increase the risk of serious infections and bleeding.(1)
PREDISPOSING FACTORS: None determined.
PATIENT MANAGEMENT: The US manufacturer of sodium iodide I 131 states that concurrent use with bone marrow depressants may enhance the depression of the hematopoetic system caused by large doses of sodium iodide I 131.(1) Sodium iodide I 131 causes a dose-dependent bone marrow suppression, including neutropenia or thrombocytopenia, in the 3 to 5 weeks following administration. Patients may be at increased risk of infections or bleeding during this time. Monitor complete blood counts within one month of therapy. If results indicate leukopenia or thrombocytopenia, dosimetry should be used to determine a safe sodium iodide I 131 activity.(1)
DISCUSSION: Hematologic disorders including death have been reported with sodium iodide I 131. The most common hematologic disorders reported include anemia, blood dyscrasias, bone marrow depression, leukopenia, and thrombocytopenia.(1)
There are no moderate interactions for this drug.
Contraindications
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- Glucose-6-phosphate dehydrogenase (g6Pd) deficiency
- Hemoglobin H disease
- Hemolytic anemia from pyruvate kinase and g6PD deficiencies
- Hepatic failure
- Lactation
- Disease of liver
- Methemoglobinemia
- NADH methemoglobin reductase deficiency
- Pregnancy
There are no moderate contraindications for this drug.
Adverse reactions
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Less Frequent
- Anemia
- Hypertension
- Leukopenia
- Thrombocytopenic disorder
Rare or Very Rare
- Abnormal hepatic function tests
- Hemolytic anemia
- Hepatic failure
- Hepatitis
- Jaundice
- Methemoglobinemia
More Frequent
- Diarrhea
- Drug-induced hot flash
- Erectile dysfunction
- Gynecomastia
- Libido changes
Less Frequent
- Anorexia
- Drowsy
- Edema
- Nausea
- Nervousness
- Symptoms of anxiety
- Vomiting
Rare or Very Rare
- Skin photosensitivity
- Urine discoloration
Precautions
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No enhanced messaging available.
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ICD codes
| Code | Type | Description |
|---|---|---|
| Prostatic carcinoma | ||
| C61 | ICD10CM | Malignant neoplasm of prostate |
ICD code information from First Databank (FDB).
Formulary status
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Last reviewed · Source: First Databank (FDB) drug data
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