Eulexin

Cytostatic Androgen Receptor Antagonists

Hazardous Drugs Classification
NIOSH 2016 List: Group 1
NIOSH (Draft) 2020 List: Table 2
Observe and exercise appropriate precautions for handling, preparation, administration, and disposal of hazardous drugs.
Use gloves to handle. Cutting, crushing, or otherwise manipulating tablets/capsules will increase exposure.

May be administered without regard to meals.

diarrhea / Early / 5.0-5.0
new primary malignancy / Delayed / 0-1.0
hepatic failure / Delayed / Incidence not known
hepatic necrosis / Delayed / Incidence not known
hepatic encephalopathy / Delayed / Incidence not known
hepatotoxicity / Delayed / Incidence not known
hemolytic anemia / Delayed / Incidence not known
methemoglobinemia / Early / Incidence not known

hot flashes / Early / 61.0-61.0
impotence (erectile dysfunction) / Delayed / 33.0-33.0
anemia / Delayed / 6.0-6.0
edema / Delayed / 4.0-4.0
leukopenia / Delayed / 3.0-3.0
jaundice / Delayed / 0-1.0
hepatitis / Delayed / 0-1.0
hypertension / Early / 1.0-1.0
thrombocytopenia / Delayed / 1.0-1.0
depression / Delayed / 1.0-1.0
confusion / Early / 1.0-1.0
hyperbilirubinemia / Delayed / Incidence not known
cholestasis / Delayed / Incidence not known
elevated hepatic enzymes / Delayed / Incidence not known

libido decrease / Delayed / 36.0-36.0
nausea / Early / 11.0-11.0
gynecomastia / Delayed / 9.0-9.0
anorexia / Delayed / 4.0-4.0
rash / Early / 3.0-3.0
drowsiness / Early / 1.0-1.0
anxiety / Delayed / 1.0-1.0
vomiting / Early / Incidence not known
abdominal pain / Early / Incidence not known
fatigue / Early / Incidence not known
photosensitivity / Delayed / Incidence not known
urine discoloration / Early / Incidence not known

Flutamide is contraindicated in patients with severe hepatic disease; it has been associated with hepatotoxicity that has resulted in hospitalization or death. Use is not recommended in patients whose ALT values exceed twice the upper limit of normal. Measure serum transaminase concentrations at baseline and then monthly for the first 4 months of therapy and periodically thereafter. Obtain liver function tests at the first sign of hepatic dysfunction. If at any time a patient has jaundice or their ALT rises above 2-times the upper limit of normal, immediately discontinue treatment and closely follow liver function tests.

Eulexin

Rx

Nonsteroidal antiandrogen; most effective in prostate cancer when used simultaneously with LHRH agonists; not effective in treating other hormonally dependent diseases such as breast cancer.

250 mg PO (two 125 mg capsules) every 8 hours for a total daily dose of 750 mg. Flutamide and LHRH therapy are initiated 8 weeks prior to the start of radiation therapy and continued during radiation therapy. Although flutamide is recommended only for use in combination with LHRH analogs, it has been used either alone or in combination with finasteride in men who wish to retain sexual potency.

250 mg PO (two 125 mg capsules) 3 times daily beginning 8 weeks prior to and continuing during radiation therapy in combination with goserelin.

250 mg (two 125 mg capsules) PO every 8 hours for a total daily dose of 750 mg. Flutamide therapy should be initiated with LHRH therapy and continued until progression.

Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no dosage adjustments are needed.

Acetaminophen; Hydrocodone: (Moderate) Hydrocodone is metabolized by CYP3A4. Flutamide, an inducer of CYP3A4, may cause increased clearance of hydrocodone, which could result in lack of efficacy or the development of an abstinence syndrome in a patient who had developed physical dependence to hydrocodone. Monitor the patient for reduced efficacy of hydrocodone. A higher hydrocodone dose may be needed if used with flutamide.
Amlodipine: (Minor) Coadministration of CYP3A4 inducers with amlodipine can theoretically increase the hepatic metabolism of amlodipine (a CYP3A4 substrate). Caution should be used when CYP3A4 inducers, such as flutamide, are coadministered with amlodipine. Monitor therapeutic response; the dosage requirements of amlodipine may be increased.
Amlodipine; Atorvastatin: (Minor) Coadministration of CYP3A4 inducers with amlodipine can theoretically increase the hepatic metabolism of amlodipine (a CYP3A4 substrate). Caution should be used when CYP3A4 inducers, such as flutamide, are coadministered with amlodipine. Monitor therapeutic response; the dosage requirements of amlodipine may be increased.
Amlodipine; Benazepril: (Minor) Coadministration of CYP3A4 inducers with amlodipine can theoretically increase the hepatic metabolism of amlodipine (a CYP3A4 substrate). Caution should be used when CYP3A4 inducers, such as flutamide, are coadministered with amlodipine. Monitor therapeutic response; the dosage requirements of amlodipine may be increased.
Amlodipine; Celecoxib: (Minor) Coadministration of CYP3A4 inducers with amlodipine can theoretically increase the hepatic metabolism of amlodipine (a CYP3A4 substrate). Caution should be used when CYP3A4 inducers, such as flutamide, are coadministered with amlodipine. Monitor therapeutic response; the dosage requirements of amlodipine may be increased.
Amlodipine; Olmesartan: (Minor) Coadministration of CYP3A4 inducers with amlodipine can theoretically increase the hepatic metabolism of amlodipine (a CYP3A4 substrate). Caution should be used when CYP3A4 inducers, such as flutamide, are coadministered with amlodipine. Monitor therapeutic response; the dosage requirements of amlodipine may be increased.
Amlodipine; Valsartan: (Minor) Coadministration of CYP3A4 inducers with amlodipine can theoretically increase the hepatic metabolism of amlodipine (a CYP3A4 substrate). Caution should be used when CYP3A4 inducers, such as flutamide, are coadministered with amlodipine. Monitor therapeutic response; the dosage requirements of amlodipine may be increased.
Amlodipine; Valsartan; Hydrochlorothiazide, HCTZ: (Minor) Coadministration of CYP3A4 inducers with amlodipine can theoretically increase the hepatic metabolism of amlodipine (a CYP3A4 substrate). Caution should be used when CYP3A4 inducers, such as flutamide, are coadministered with amlodipine. Monitor therapeutic response; the dosage requirements of amlodipine may be increased.
Aprepitant, Fosaprepitant: (Major) Use caution if flutamide and aprepitant are used concurrently and monitor for a possible decrease in the efficacy of aprepitant as well as an increase in flutamide-related adverse effects for several days after administration of a multi-day aprepitant regimen. After administration, fosaprepitant is rapidly converted to aprepitant and shares the same drug interactions. Flutamide is a CYP3A4 substrate in vitro. Aprepitant, when administered as a 3-day oral regimen (125 mg/80 mg/80 mg), is a moderate CYP3A4 inhibitor and inducer; substitution of fosaprepitant 115 mg IV on day 1 of the 3-day regimen may lessen the inhibitory effects of CYP3A4. The AUC of a single dose of another CYP3A4 substrate, midazolam, increased by 2.3-fold and 3.3-fold on days 1 and 5, respectively, when coadministered with a 5-day oral aprepitant regimen. After a 3-day oral aprepitant regimen, the AUC of midazolam increased by 25% on day 4, and decreased by 19% and 4% on days 8 and 15, respectively, when given on days 1, 4, 8, and 15. As a single 40-mg oral dose, the inhibitory effect of aprepitant on CYP3A4 is weak, with the AUC of midazolam increased by 1.2-fold; the midazolam AUC increased by 1.5-fold after a single 125-mg dose of oral aprepitant. After single doses of IV fosaprepitant, the midazolam AUC increased by 1.8-fold (150 mg) and 1.6-fold (100 mg); less than a 2-fold increase in the midazolam AUC is not considered clinically important. Additionally, flutamide is a moderate in vitro CYP3A4 inducer and aprepitant is a CYP3A4 substrate. When a single dose of aprepitant (375 mg, or 3 times the maximum recommended dose) was administered on day 9 of a 14-day rifampin regimen (a strong CYP3A4 inducer), the AUC of aprepitant decreased approximately 11-fold and the mean terminal half-life decreased by 3-fold. The manufacturer of aprepitant recommends avoidance of administration with strong CYP3A4 inducers, but does not provide guidance for weak-to-moderate inducers.
Articaine; Epinephrine: (Moderate) Coadministration of articaine with oxidizing agents, such as flutamide, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue articaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Atazanavir: (Major) Caution is warranted when atazanavir is administered with flutamide as there is a potential for elevated flutamide concentrations and decreased concentrations of atazanavir. Decreased antiretroviral concentrations may lead to a reduction of antiretroviral efficacy and the potential development of viral resistance. Flutamide is a substrate and inducer of CYP3A4. Atazanavir is a CYP3A4 substrate and inhibitor.
Atazanavir; Cobicistat: (Major) Caution is warranted when atazanavir is administered with flutamide as there is a potential for elevated flutamide concentrations and decreased concentrations of atazanavir. Decreased antiretroviral concentrations may lead to a reduction of antiretroviral efficacy and the potential development of viral resistance. Flutamide is a substrate and inducer of CYP3A4. Atazanavir is a CYP3A4 substrate and inhibitor. (Major) Caution is warranted when cobicistat is administered with flutamide as there is a potential for elevated flutamide concentrations and decreased concentrations of cobicistat. Decreased antiretroviral concentrations may lead to a reduction of antiretroviral efficacy and the potential development of viral resistance. Flutamide is a substrate and inducer of CYP3A4. Cobicistat is a CYP3A4 substrate and inhibitor.
Bromocriptine: (Moderate) Caution and close monitoring are advised if bromocriptine and flutamide are used together. Concurrent use may decrease the plasma concentrations of bromocriptine resulting in loss of efficacy. Bromocriptine is extensively metabolized by the liver via CYP3A4; in vitro data show that flutamide is a moderate inducer of CYP3A4.
Bupivacaine Liposomal: (Moderate) Coadministration of bupivacaine with oxidizing agents, such as flutamide, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue bupivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Bupivacaine: (Moderate) Coadministration of bupivacaine with oxidizing agents, such as flutamide, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue bupivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Bupivacaine; Epinephrine: (Moderate) Coadministration of bupivacaine with oxidizing agents, such as flutamide, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue bupivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Bupivacaine; Lidocaine: (Moderate) Coadministration of bupivacaine with oxidizing agents, such as flutamide, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue bupivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen. (Moderate) Coadministration of lidocaine with oxidizing agents, such as flutamide, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Bupivacaine; Meloxicam: (Moderate) Coadministration of bupivacaine with oxidizing agents, such as flutamide, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue bupivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Cabotegravir; Rilpivirine: (Moderate) Close clinical monitoring is advised when administering flutamide with rilpivirine due to the potential for rilpivirine treatment failure. Although this interaction has not been studied, predictions can be made based on metabolic pathways. Flutamide is an inducer of the hepatic isoenzyme CYP3A4; rilpivirine is metabolized by this isoenzyme. Coadministration may result in decreased rilpivirine serum concentrations and impaired virologic response.
Chloroprocaine: (Moderate) Coadministration of chloroprocaine with oxidizing agents, such as flutamide, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue chloroprocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Chlorpheniramine; Hydrocodone: (Moderate) Hydrocodone is metabolized by CYP3A4. Flutamide, an inducer of CYP3A4, may cause increased clearance of hydrocodone, which could result in lack of efficacy or the development of an abstinence syndrome in a patient who had developed physical dependence to hydrocodone. Monitor the patient for reduced efficacy of hydrocodone. A higher hydrocodone dose may be needed if used with flutamide.
Ciprofloxacin: (Moderate) Coadministration of ciprofloxacin and flutamide could lead to increases in the serum concentrations of flutamide. Ciprofloxacin has been shown to inhibit CYP1A2 and CYP3A4 and flutamide is a substrate of these enzymes.
Cobicistat: (Major) Caution is warranted when cobicistat is administered with flutamide as there is a potential for elevated flutamide concentrations and decreased concentrations of cobicistat. Decreased antiretroviral concentrations may lead to a reduction of antiretroviral efficacy and the potential development of viral resistance. Flutamide is a substrate and inducer of CYP3A4. Cobicistat is a CYP3A4 substrate and inhibitor.
Cobimetinib: (Major) Avoid the concurrent use of cobimetinib with flutamide due to decreased cobimetinib efficacy. Cobimetinib is a CYP3A substrate in vitro, and flutamide is a moderate in vitro inducer of CYP3A. Based on simulations, cobimetinib exposure would decrease by 73% when coadministered with a moderate CYP3A inducer.
Daclatasvir: (Major) The dose of daclatasvir, a CYP3A4 substrate, must be increased to 90 mg PO once daily when administered in combination with moderate CYP3A4 inducers, such as flutamide. Taking these drugs together may decrease daclatasvir serum concentrations, potentially resulting in reduced antiviral efficacy and antimicrobial resistance.
Dapsone: (Moderate) The metabolism of dapsone may be accelerated when administered concurrently with flutamide, a known inducer of CYP3A4. Coadministration is expected to decrease the plasma concentration of dapsone and increase the formation of dapsone hydroxylamine (a metabolite associated with hemolysis). If these drugs must be administered together, closely monitor for a reduction in dapsone efficacy and signs of hemolytic anemia.
Darunavir: (Major) Caution is warranted when darunavir; cobicistat is administered with flutamide as there is a potential for elevated flutamide concentrations and decreased concentrations of darunavir. Decreased antiretroviral concentrations may lead to a reduction of antiretroviral efficacy and the potential development of viral resistance. Flutamide is a substrate and inducer of CYP3A4. Darunavir is a CYP3A4 substrate and inhibitor.
Darunavir; Cobicistat: (Major) Caution is warranted when cobicistat is administered with flutamide as there is a potential for elevated flutamide concentrations and decreased concentrations of cobicistat. Decreased antiretroviral concentrations may lead to a reduction of antiretroviral efficacy and the potential development of viral resistance. Flutamide is a substrate and inducer of CYP3A4. Cobicistat is a CYP3A4 substrate and inhibitor. (Major) Caution is warranted when darunavir; cobicistat is administered with flutamide as there is a potential for elevated flutamide concentrations and decreased concentrations of darunavir. Decreased antiretroviral concentrations may lead to a reduction of antiretroviral efficacy and the potential development of viral resistance. Flutamide is a substrate and inducer of CYP3A4. Darunavir is a CYP3A4 substrate and inhibitor.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Major) Caution is warranted when cobicistat is administered with flutamide as there is a potential for elevated flutamide concentrations and decreased concentrations of cobicistat. Decreased antiretroviral concentrations may lead to a reduction of antiretroviral efficacy and the potential development of viral resistance. Flutamide is a substrate and inducer of CYP3A4. Cobicistat is a CYP3A4 substrate and inhibitor. (Major) Caution is warranted when darunavir; cobicistat is administered with flutamide as there is a potential for elevated flutamide concentrations and decreased concentrations of darunavir. Decreased antiretroviral concentrations may lead to a reduction of antiretroviral efficacy and the potential development of viral resistance. Flutamide is a substrate and inducer of CYP3A4. Darunavir is a CYP3A4 substrate and inhibitor.
Deflazacort: (Major) Avoid concomitant use of deflazacort and flutamide. Concurrent use may significantly decrease concentrations of 21-desDFZ, the active metabolite of deflazacort, resulting in loss of efficacy. Deflazacort is a CYP3A4 substrate; flutamide is a moderate inducer of CYP3A4. Administration of deflazacort with multiple doses of rifampin (a strong CYP3A4 inducer) resulted in geometric mean exposures that were approximately 95% lower compared to administration alone.
Dolutegravir; Rilpivirine: (Moderate) Close clinical monitoring is advised when administering flutamide with rilpivirine due to the potential for rilpivirine treatment failure. Although this interaction has not been studied, predictions can be made based on metabolic pathways. Flutamide is an inducer of the hepatic isoenzyme CYP3A4; rilpivirine is metabolized by this isoenzyme. Coadministration may result in decreased rilpivirine serum concentrations and impaired virologic response.
Doxorubicin Liposomal: (Major) In vitro, flutamide is a CYP3A4 inhibitor; doxorubicin is a major CYP3A4 substrate. Clinically significant interactions have been reported when doxorubicin was coadministered with inhibitors of CYP3A4, resulting in increased concentration and clinical effect of doxorubicin. Avoid coadministration of flutamide and doxorubicin if possible. If not possible, closely monitor for increased side effects of doxorubicin including myelosuppression and cardiotoxicity.
Doxorubicin: (Major) In vitro, flutamide is a CYP3A4 inhibitor; doxorubicin is a major CYP3A4 substrate. Clinically significant interactions have been reported when doxorubicin was coadministered with inhibitors of CYP3A4, resulting in increased concentration and clinical effect of doxorubicin. Avoid coadministration of flutamide and doxorubicin if possible. If not possible, closely monitor for increased side effects of doxorubicin including myelosuppression and cardiotoxicity.
Dronabinol: (Moderate) Use caution if coadministration of dronabinol with flutamide is necessary, and monitor for a decrease in the efficacy of dronabinol. Dronabinol is a CYP2C9 and 3A4 substrate; flutamide is a moderate inducer of CYP3A4 in vitro. Concomitant use may result in decreased plasma concentrations of dronabinol.
Dronedarone: (Major) The concomitant use of dronedarone and CYP3A4 inducers should be avoided. Dronedarone is metabolized by CYP3A and is an inhibitor of CYP3A. Flutamide induces and is a substrate for CYP3A4. Coadministration of CYP3A4 inducers, such as flutamide, with dronedarone may result in reduced plasma concentration and subsequent reduced effectiveness of dronedarone therapy; plasma concentrations of flutamide may also be increased.
Elbasvir; Grazoprevir: (Major) If possible, avoid concurrent administration of elbasvir with flutamide. Flutamide is a moderate CYP3A inducer, while elbasvir is a substrate of CYP3A. Use of these drugs together is expected to decrease the plasma concentrations of elbasvir, and may result in decreased virologic response. (Major) If possible, avoid concurrent administration of grazoprevir with flutamide. Flutamide is a moderate CYP3A inducer, while grazoprevir is a substrate of CYP3A. Use of these drugs together is expected to decrease the plasma concentrations of grazoprevir, and may result in decreased virologic response. Conversely, concentrations of flutamide (also a CYP3A substrate) may be increased when given with grazoprevir (a weak CYP3A inhibitor).
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Major) Caution is warranted when cobicistat is administered with flutamide as there is a potential for elevated flutamide concentrations and decreased concentrations of cobicistat. Decreased antiretroviral concentrations may lead to a reduction of antiretroviral efficacy and the potential development of viral resistance. Flutamide is a substrate and inducer of CYP3A4. Cobicistat is a CYP3A4 substrate and inhibitor. (Major) Caution is warranted when elvitegravir is administered with flutamide as there is a potential for decreased concentrations of elvitegravir. Decreased antiretroviral concentrations may lead to a reduction of antiretroviral efficacy and the potential development of viral resistance. Flutamide is a substrate and inducer of CYP3A4. Elvitegravir is a CYP3A4 substrate.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Major) Caution is warranted when cobicistat is administered with flutamide as there is a potential for elevated flutamide concentrations and decreased concentrations of cobicistat. Decreased antiretroviral concentrations may lead to a reduction of antiretroviral efficacy and the potential development of viral resistance. Flutamide is a substrate and inducer of CYP3A4. Cobicistat is a CYP3A4 substrate and inhibitor. (Major) Caution is warranted when elvitegravir is administered with flutamide as there is a potential for decreased concentrations of elvitegravir. Decreased antiretroviral concentrations may lead to a reduction of antiretroviral efficacy and the potential development of viral resistance. Flutamide is a substrate and inducer of CYP3A4. Elvitegravir is a CYP3A4 substrate.
Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Moderate) Close clinical monitoring is advised when administering flutamide with rilpivirine due to the potential for rilpivirine treatment failure. Although this interaction has not been studied, predictions can be made based on metabolic pathways. Flutamide is an inducer of the hepatic isoenzyme CYP3A4; rilpivirine is metabolized by this isoenzyme. Coadministration may result in decreased rilpivirine serum concentrations and impaired virologic response.
Emtricitabine; Rilpivirine; Tenofovir Disoproxil Fumarate: (Moderate) Close clinical monitoring is advised when administering flutamide with rilpivirine due to the potential for rilpivirine treatment failure. Although this interaction has not been studied, predictions can be made based on metabolic pathways. Flutamide is an inducer of the hepatic isoenzyme CYP3A4; rilpivirine is metabolized by this isoenzyme. Coadministration may result in decreased rilpivirine serum concentrations and impaired virologic response.
Guaifenesin; Hydrocodone: (Moderate) Hydrocodone is metabolized by CYP3A4. Flutamide, an inducer of CYP3A4, may cause increased clearance of hydrocodone, which could result in lack of efficacy or the development of an abstinence syndrome in a patient who had developed physical dependence to hydrocodone. Monitor the patient for reduced efficacy of hydrocodone. A higher hydrocodone dose may be needed if used with flutamide.
Homatropine; Hydrocodone: (Moderate) Hydrocodone is metabolized by CYP3A4. Flutamide, an inducer of CYP3A4, may cause increased clearance of hydrocodone, which could result in lack of efficacy or the development of an abstinence syndrome in a patient who had developed physical dependence to hydrocodone. Monitor the patient for reduced efficacy of hydrocodone. A higher hydrocodone dose may be needed if used with flutamide.
Hydrocodone: (Moderate) Hydrocodone is metabolized by CYP3A4. Flutamide, an inducer of CYP3A4, may cause increased clearance of hydrocodone, which could result in lack of efficacy or the development of an abstinence syndrome in a patient who had developed physical dependence to hydrocodone. Monitor the patient for reduced efficacy of hydrocodone. A higher hydrocodone dose may be needed if used with flutamide.
Hydrocodone; Ibuprofen: (Moderate) Hydrocodone is metabolized by CYP3A4. Flutamide, an inducer of CYP3A4, may cause increased clearance of hydrocodone, which could result in lack of efficacy or the development of an abstinence syndrome in a patient who had developed physical dependence to hydrocodone. Monitor the patient for reduced efficacy of hydrocodone. A higher hydrocodone dose may be needed if used with flutamide.
Hydrocodone; Pseudoephedrine: (Moderate) Hydrocodone is metabolized by CYP3A4. Flutamide, an inducer of CYP3A4, may cause increased clearance of hydrocodone, which could result in lack of efficacy or the development of an abstinence syndrome in a patient who had developed physical dependence to hydrocodone. Monitor the patient for reduced efficacy of hydrocodone. A higher hydrocodone dose may be needed if used with flutamide.
Ibrutinib: (Moderate) Use ibrutinib and flutamide together with caution; decreased ibrutinib levels may occur resulting in reduced ibrutinib efficacy. Monitor patients for signs of decreased ibrutinib efficacy if these agents are used together. Ibrutinib is a CYP3A4 substrate; flutamide is a moderate CYP3A inducer. Simulations suggest that coadministration with a moderate CYP3A4 inducer may decrease ibrutinib exposure by 3-fold.
Idelalisib: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with flutamide, a CYP3A substrate, as flutamide toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Isavuconazonium: (Major) Concomitant use of isavuconazonium with flutamide may result in increased serum concentrations of flutamide and decreased serum concentrations of isavuconazonium. Flutamide is a substrate and inducer of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a sensitive substrate and moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Levamlodipine: (Minor) Coadministration of CYP3A4 inducers with amlodipine can theoretically increase the hepatic metabolism of amlodipine (a CYP3A4 substrate). Caution should be used when CYP3A4 inducers, such as flutamide, are coadministered with amlodipine. Monitor therapeutic response; the dosage requirements of amlodipine may be increased.
Lidocaine: (Moderate) Coadministration of lidocaine with oxidizing agents, such as flutamide, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Lidocaine; Epinephrine: (Moderate) Coadministration of lidocaine with oxidizing agents, such as flutamide, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Lidocaine; Prilocaine: (Moderate) Coadministration of lidocaine with oxidizing agents, such as flutamide, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue lidocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen. (Moderate) Coadministration of prilocaine with oxidizing agents, such as flutamide, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue prilocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Maraviroc: (Moderate) Use caution if coadministration of maraviroc with flutamide is necessary, due to a possible decrease in maraviroc exposure. Maraviroc is a CYP3A substrate. Flutamide is an inducer of CYP3A4 in vitro but the clinical significance of this finding is unknown. Monitor for a decrease in maraviroc efficacy with concomitant use.
Mepivacaine: (Moderate) Coadministration of mepivacaine with oxidizing agents, such as flutamide, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue mepivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Mitotane: (Major) Use caution if mitotane and flutamide are used concomitantly, and monitor for decreased efficacy of flutamide and a possible change in dosage requirements. Mitotane is a strong CYP3A4 inducer and flutamide is a CYP3A4 substrate in vitro; coadministration may result in decreased plasma concentrations of flutamide.
Obeticholic Acid: (Moderate) Obeticholic acid may increase the exposure to concomitant drugs that are CYP1A2 substrates, such as flutamide. Therapeutic monitoring is recommended with coadministration.
Olmesartan; Amlodipine; Hydrochlorothiazide, HCTZ: (Minor) Coadministration of CYP3A4 inducers with amlodipine can theoretically increase the hepatic metabolism of amlodipine (a CYP3A4 substrate). Caution should be used when CYP3A4 inducers, such as flutamide, are coadministered with amlodipine. Monitor therapeutic response; the dosage requirements of amlodipine may be increased.
Pazopanib: (Moderate) Pazopanib is a substrate for and a weak inhibitor of CYP3A4. Coadministration of pazopanib and flutamide, a CYP3A4 substrate, may cause an increase in systemic concentrations of flutamide. In addition, flutamide is an inducer of CYP3A4 and may cause a decrease in systemic concentrations of pazopanib. Use caution when administering these drugs concomitantly.
Peginterferon Alfa-2b: (Moderate) Monitor for adverse effects associated with increased exposure to flutamide if peginterferon alfa-2b is coadministered. Peginterferon alfa-2b is a CYP1A2 inhibitor, while flutamide is a CYP1A2 substrate.
Penicillin G Benzathine; Penicillin G Procaine: (Moderate) Coadministration of penicillin G procaine with oxidizing agents, such as flutamide, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue penicillin G procaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Penicillin G Procaine: (Moderate) Coadministration of penicillin G procaine with oxidizing agents, such as flutamide, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue penicillin G procaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Perindopril; Amlodipine: (Minor) Coadministration of CYP3A4 inducers with amlodipine can theoretically increase the hepatic metabolism of amlodipine (a CYP3A4 substrate). Caution should be used when CYP3A4 inducers, such as flutamide, are coadministered with amlodipine. Monitor therapeutic response; the dosage requirements of amlodipine may be increased.
Pexidartinib: (Moderate) Monitor for evidence of hepatotoxicity if pexidartinib is coadministered with flutamide. Avoid concurrent use in patients with increased serum transaminases, total bilirubin, or direct bilirubin (more than ULN) or active liver or biliary tract disease.
Posaconazole: (Moderate) Posaconazole and flutamide should be coadministered with caution due to an increased potential for flutamide-related adverse events. Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of flutamide. These drugs used in combination may result in elevated flutamide plasma concentrations, causing an increased risk for flutamide-related adverse events.
Praziquantel: (Major) In vitro and drug interactions studies suggest that the CYP3A4 isoenzyme is the major enzyme involved in praziquantel metabolism. Therefore, use of praziquantel with flutamide, a CYP3A4 inducer, should be done with caution as concomitant use may produce therapeutically ineffective concentrations of praziquantel.
Pretomanid: (Major) Avoid coadministration of pretomanid with flutamide, especially in patients with impaired hepatic function, due to increased risk for hepatotoxicity. Monitor for evidence of hepatotoxicity if coadministration is necessary. If new or worsening hepatic dysfunction occurs, discontinue hepatotoxic medications.
Prilocaine: (Moderate) Coadministration of prilocaine with oxidizing agents, such as flutamide, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue prilocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Prilocaine; Epinephrine: (Moderate) Coadministration of prilocaine with oxidizing agents, such as flutamide, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue prilocaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Rilpivirine: (Moderate) Close clinical monitoring is advised when administering flutamide with rilpivirine due to the potential for rilpivirine treatment failure. Although this interaction has not been studied, predictions can be made based on metabolic pathways. Flutamide is an inducer of the hepatic isoenzyme CYP3A4; rilpivirine is metabolized by this isoenzyme. Coadministration may result in decreased rilpivirine serum concentrations and impaired virologic response.
Riluzole: (Moderate) Monitor for signs and symptoms of hepatic injury during coadministration of riluzole and flutamide. Concomitant use may increase the risk for hepatotoxicity. Discontinue riluzole if clinical signs of liver dysfunction are present.
Rivaroxaban: (Minor) Coadministration of rivaroxaban and flutamide may result in decreased rivaroxaban exposure and may decrease the efficacy of rivaroxaban. Flutamide is an inducer of CYP3A4, and rivaroxaban is a substrate of CYP3A4. If these drugs are administered concurrently, monitor the patient for signs of lack of efficacy of rivaroxaban.
Romidepsin: (Moderate) Romidepsin is a substrate for CYP3A4. Coadministration of a CYP3A4 inducer, like flutamide, may decrease systemic concentrations of romidepsin. Use caution when concomitant administration of these agents is necessary.
Ropivacaine: (Moderate) Coadministration of ropivacaine with oxidizing agents, such as flutamide, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue ropivacaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Ruxolitinib: (Moderate) Ruxolitinib is a CYP3A4 substrate. When used with drugs that are CYP3A4 inducers such as flutamide, a dose adjustment is not necessary, but closely monitor patients and titrate the ruxolitinib dose based on safety and efficacy. The Cmax and AUC of a single 50 mg dose of ruxolitinib was decreased by 32% and 61%, respectively, after rifampin 600 mg once daily was administered for 10 days. The relative exposure to ruxolitinib's active metabolites increased by about 100%, which may partially explain the reported disproportionate 10% reduction in the pharmacodynamic marker pSTAT3 inhibition.
Sofosbuvir; Velpatasvir: (Major) Avoid coadministration of velpatasvir with flutamide. Taking these drugs together may significantly decrease velpatasvir plasma concentrations, potentially resulting in loss of antiviral efficacy. Velpatasvir is a CYP3A4 substrate; flutamide is an inducer of CYP3A4.
Sofosbuvir; Velpatasvir; Voxilaprevir: (Major) Avoid coadministration of velpatasvir with flutamide. Taking these drugs together may significantly decrease velpatasvir plasma concentrations, potentially resulting in loss of antiviral efficacy. Velpatasvir is a CYP3A4 substrate; flutamide is an inducer of CYP3A4.
Telmisartan; Amlodipine: (Minor) Coadministration of CYP3A4 inducers with amlodipine can theoretically increase the hepatic metabolism of amlodipine (a CYP3A4 substrate). Caution should be used when CYP3A4 inducers, such as flutamide, are coadministered with amlodipine. Monitor therapeutic response; the dosage requirements of amlodipine may be increased.
Terbinafine: (Moderate) Due to the risk for breakthrough fungal infections, caution is advised when administering terbinafine with flutamide. Although this interaction has not been studied by the manufacturer, and published literature suggests the potential for interactions to be low, taking these drugs together may decrease the systemic exposure of terbinafine. Predictions about the interaction can be made based on the metabolic pathways of both drugs. Terbinafine is metabolized by at least 7 CYP isoenyzmes, with major contributions coming from CYP3A4; flutamide induces this enzyme. Monitor patients for breakthrough fungal infections.
Tetracaine: (Moderate) Coadministration of tetracaine with oxidizing agents, such as flutamide, may increase the risk of developing methemoglobinemia. Monitor patients closely for signs and symptoms of methemoglobinemia if coadministration is necessary. If methemoglobinemia occurs or is suspected, discontinue tetracaine and any other oxidizing agents. Depending on the severity of symptoms, patients may respond to supportive care; more severe symptoms may require treatment with methylene blue, exchange transfusion, or hyperbaric oxygen.
Tolvaptan: (Major) Tolvaptan is metabolized by CYP3A4. Flutamide is an inducer of CYP3A4. Coadministration may result in reduced plasma concentration and subsequent reduced effectiveness of tolvaptan therapy and should be avoided. If coadministration is unavoidable, an increase in the tolvaptan dose may be necessary and patients should be monitored for decreased effectiveness of tolvaptan.
Trabectedin: (Minor) Use caution if coadministration of trabectedin and flutamide is necessary, due to the risk of decreased trabectedin exposure. Trabectedin is a CYP3A substrate and, in vitro, flutamide is a moderate CYP3A inducer. Coadministration with rifampin (600 mg daily for 6 days), a strong CYP3A inducer, decreased the systemic exposure of a single dose of trabectedin by 31% and the Cmax by 21% compared to a single dose of trabectedin given alone. The manufacturer of trabectedin recommends avoidance of coadministration with strong CYP3A inducers; there are no recommendations for concomitant use of moderate or weak CYP3A inducers.
Ulipristal: (Moderate) Ulipristal is a substrate of CYP3A4 and flutamide is a CYP3A4 inducer. Concomitant use may decrease the plasma concentration and effectiveness of ulipristal.
Vemurafenib: (Major) Concomitant use of vemurafenib and flutamide may result in altered concentrations of flutamide and decreased concentrations vemurafenib. Vemurafenib is a substrate/inducer of CYP3A4 and an inhibitor of CYP1A2. Flutamide is a substrate/inducer of CYP3A4 and substrate of CYP1A2. Use caution and monitor patients for toxicity and efficacy.
Vincristine Liposomal: (Moderate) Vincristine is a substrate for cytochrome P450 (CYP) 3A4. Agents that induce CYP3A4 may increase the metabolism of vincristine and decrease the efficacy of drug, including flutamide (in vitro). Patients receiving these drugs concurrently with vincristine should be monitored for possible loss of vincristine efficacy.
Vincristine: (Moderate) Vincristine is a substrate for cytochrome P450 (CYP) 3A4. Agents that induce CYP3A4 may increase the metabolism of vincristine and decrease the efficacy of drug, including flutamide (in vitro). Patients receiving these drugs concurrently with vincristine should be monitored for possible loss of vincristine efficacy.
Vorapaxar: (Moderate) Use caution during concurrent use of vorapaxar and flutamide. Decreased serum concentrations of vorapaxar and thus decreased efficacy are possible when vorapaxar, a CYP3A4 substrate, is coadministered with flutamide, an inducer of CYP3A4 in vitro.
Warfarin: (Moderate) Prothrombin times and/or INRs have increased in patients receiving long-term warfarin therapy who are given flutamide. Adjustment of the warfarin dose may be required during flutamide therapy.

Eulexin/Flutamide Oral Cap: 125mg

750 mg/day PO.

750 mg/day PO.

Safety and efficacy have not been established.

Safety and efficacy have not been established.

The antiandrogenic effects of flutamide are mediated by the inhibition of the uptake and/or nuclear binding of testosterone and dihydrotestosterone by prostatic tissue. This tumor is androgen-sensitive and generally will respond to any treatment that counteracts the effects of androgens. Therefore, flutamide-induced inhibition of androgens at the cellular level complements the castration effects of LHRH agonists. Flutamide is also effective when used alone. The best response is seen in untreated patients.

Flutamide is administered orally. The drug is 95% plasma protein-bound and appears to concentrate in the prostate. It undergoes rapid metabolism to a variety of compounds, and over 95% of an oral dose is excreted by the kidneys. Due to the high protein binding, it is not removed by hemodialysis.
 
Affected cytochrome P450 isoenzymes: CYP1A2, CYP3A4
Flutamide is a substrate of CYP1A2 and CYP3A4; in vitro study has demonstrated that the CYP1A2 isoenzyme is the major pathway and the CYP3A4 isoenyzme is the minor pathway for metabolism. There is potential for drug interactions when CYP1A2 inducers or inhibitors are coadministered. Flutamide is an inducer of CYP3A4 in vitro but the clinical significance of this finding is unknown.

Flutamide is rapidly and completely absorbed across the GI tract following oral administration. Food has no effect on the bioavailability of flutamide. The absolute bioavailability is unknown.

Given its indication for use, flutamide would not be expected to be used during lactation. Use of flutamide during breast-feeding is not indicated, and if excreted in milk, would be expected to have the potential adverse effects in a nursing infant due to the anti-androgenic activity.