Casodex

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.

Bicalutamide should be taken at the same time every day.
May be administered without regard to meals.
If a dose is missed, skip that dose and take the next dose at the usual time; do not take the missed dose and do not take a double dose.

impotence (erectile dysfunction) / Delayed / 7.0-7.0
cardiac arrest / Early / 2.0-5.0
myocardial infarction / Delayed / 2.0-5.0
GI bleeding / Delayed / 2.0-5.0
new primary malignancy / Delayed / 2.0-5.0
heart failure / Delayed / 2.0-5.0
bone fractures / Delayed / 4.0-4.0
pulmonary fibrosis / Delayed / Incidence not known
hepatic failure / Delayed / Incidence not known
hepatotoxicity / Delayed / Incidence not known
angioedema / Rapid / Incidence not known

hot flashes / Early / 53.0-53.0
constipation / Delayed / 22.0-22.0
dyspnea / Early / 13.0-13.0
peripheral edema / Delayed / 13.0-13.0
hematuria / Delayed / 12.0-12.0
anemia / Delayed / 11.0-11.0
bone pain / Delayed / 9.0-9.0
chest pain (unspecified) / Early / 8.0-8.0
myasthenia / Delayed / 7.0-7.0
elevated hepatic enzymes / Delayed / 7.0-7.0
hyperglycemia / Delayed / 6.0-6.0
angina / Early / 2.0-5.0
melena / Delayed / 2.0-5.0
urinary retention / Early / 5.0-5.0
dysuria / Early / 2.0-5.0
edema / Delayed / 2.0-5.0
dysphagia / Delayed / 2.0-5.0
cataracts / Delayed / 2.0-5.0
dehydration / Delayed / 2.0-5.0
gout / Delayed / 2.0-5.0
hypercholesterolemia / Delayed / 2.0-5.0
hypertonia / Delayed / 2.0-5.0
confusion / Early / 2.0-5.0
urinary incontinence / Early / 4.0-4.0
depression / Delayed / 4.0-4.0
leukopenia / Delayed / Incidence not known
pneumonitis / Delayed / Incidence not known
interstitial lung disease / Delayed / Incidence not known
hyperbilirubinemia / Delayed / Incidence not known
hepatitis / Delayed / Incidence not known
hypertension / Early / Incidence not known

gynecomastia / Delayed / 9.0-38.0
back pain / Delayed / 25.0-25.0
asthenia / Delayed / 22.0-22.0
pelvic pain / Delayed / 21.0-21.0
infection / Delayed / 18.0-18.0
nausea / Early / 15.0-15.0
diarrhea / Early / 12.0-12.0
nocturia / Early / 12.0-12.0
abdominal pain / Early / 11.0-11.0
dizziness / Early / 10.0-10.0
rash / Early / 9.0-9.0
cough / Delayed / 8.0-8.0
pharyngitis / Delayed / 8.0-8.0
paresthesias / Delayed / 8.0-8.0
headache / Early / 7.0-7.0
influenza / Delayed / 7.0-7.0
weight loss / Delayed / 7.0-7.0
dyspepsia / Early / 7.0-7.0
insomnia / Early / 7.0-7.0
flatulence / Early / 6.0-6.0
increased urinary frequency / Early / 6.0-6.0
diaphoresis / Early / 6.0-6.0
anorexia / Delayed / 6.0-6.0
vomiting / Early / 6.0-6.0
myalgia / Early / 2.0-5.0
muscle cramps / Delayed / 2.0-5.0
syncope / Early / 2.0-5.0
pruritus / Rapid / 2.0-5.0
xerosis / Delayed / 2.0-5.0
urinary urgency / Early / 2.0-5.0
anxiety / Delayed / 5.0-5.0
weight gain / Delayed / 5.0-5.0
xerostomia / Early / 2.0-5.0
chills / Rapid / 2.0-5.0
fever / Early / 2.0-5.0
drowsiness / Early / 2.0-5.0
alopecia / Delayed / 2.0-5.0
libido decrease / Delayed / 2.0-5.0
epistaxis / Delayed / 2.0-5.0
rhinitis / Early / 4.0-4.0
photosensitivity / Delayed / Incidence not known
urticaria / Rapid / Incidence not known

Casodex

Rx

Oral nonsteroidal antiandrogen
Used for the treatment of metastatic prostatic carcinoma
Can cause hepatotoxicity; monitor liver function tests

50 mg PO once daily. Treatment with bicalutamide should be started at the same time as treatment with an LHRH analog. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. There was no significant difference in survival between previously untreated patients with advanced prostate cancer who received bicalutamide compared with flutamide, each in combination with LHRH analogs. Additionally, there was no significant difference in time to objective tumor progression. Assessment of quality of life questionnaires did not indicate consistent significant differences between the 2 treatment groups. Due to strong evidence supporting the use of docetaxel, abiraterone plus prednisone, apalutamide, or enzalutamide in combination with androgen deprivation therapy in men with newly diagnosed metastatic hormone-sensitive prostate cancer, the long-term use of first-generation antiandrogens such as bicalutamide is not recommended in American Urological Association guidelines for the treatment of advanced prostate cancer.

Case reports suggest 50 mg PO once every other day is effective; additionally, a lower dose of 1 to 2 doses per week has also been successful. Coadministration of certain drugs may need to be avoided or dosage adjustments may be necessary; review drug interactions. In 2 patients (both with sickle cell anemia), an initial dose of 50 mg PO once daily eliminated stuttering priapism; due to financial reasons or adverse effects (e.g., gynecomastia), the dose was reduced to 50 mg PO every other day with continued successful prevention of priapism. The patient experiencing gynecomastia further reduced his dosage to 50 mg PO 1 to 2 times per week with success. A third patient, with a spinal cord injury, experienced complete elimination of priapism after initiating therapy with 50 mg PO every other day. All 3 patients have been treated chronically (i.e., greater than 2 years) without recurrence of priapism or significant adverse effects; all 3 patients are able to engage in sexual activity. The American Urological Association recommends antiandrogen therapy as a first-line option in the prevention of stuttering priapism; however, do not use bicalutamide in patients who have not achieved full sexual maturation and adult stature.

†Indicates off-label use

No dosage adjustment is necessary.
 
Jaundice, or ALT greater than 2 times the upper limit of normal: Discontinue bicalutamide treatment.

No dosage adjustment is necessary.

Acetaminophen; Caffeine; Dihydrocodeine: (Moderate) Concomitant use of dihydrocodeine with bicalutamide may increase dihydrocodeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased dihydromorphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of dihydrocodeine until stable drug effects are achieved. Discontinuation of bicalutamide could decrease dihydrocodeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to dihydrocodeine. If bicalutamide is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Bicalutamide is a weak inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of dihydrocodeine.
Acetaminophen; Hydrocodone: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of bicalutamide is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like bicalutamide can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If bicalutamide is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
Acetaminophen; Oxycodone: (Moderate) Consider a reduced dose of oxycodone with frequent monitoring for respiratory depression and sedation if concurrent use of bicalutamide is necessary. If bicalutamide is discontinued, consider increasing the oxycodone dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oxycodone is a CYP3A4 substrate, and coadministration with a weak inhibitor like bicalutamide can increase oxycodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of oxycodone. If bicalutamide is discontinued, oxycodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to oxycodone.
Alfentanil: (Moderate) Consider a reduced dose of alfentanil with frequent monitoring for respiratory depression and sedation if concurrent use of bicalutamide is necessary. If bicalutamide is discontinued, consider increasing the alfentanil dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Alfentanil is a sensitive CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like bicalutamide can increase alfentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of alfentanil. If bicalutamide is discontinued, alfentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to alfentanil.
Alprazolam: (Major) Avoid coadministration of alprazolam and bicalutamide due to the potential for elevated alprazolam concentrations, which may cause prolonged sedation and respiratory depression. If coadministration is necessary, consider reducing the dose of alprazolam as clinically appropriate and monitor for an increase in alprazolam-related adverse reactions. Lorazepam, oxazepam, or temazepam may be safer alternatives if a benzodiazepine must be administered in combination with bicalutamide, as these benzodiazepines are not oxidatively metabolized. Alprazolam is a CYP3A4 substrate and bicalutamide is a weak CYP3A4 inhibitor. Coadministration with another weak CYP3A4 inhibitor, increased alprazolam maximum concentration by 82%, decreased clearance by 42%, and increased half-life by 16%.
Aripiprazole: (Moderate) Monitor for aripiprazole-related adverse reactions during concomitant use of bicalutamide. Patients receiving both a CYP2D6 inhibitor plus bicalutamide may require an aripiprazole dosage adjustment. Dosing recommendations vary based on aripiprazole dosage form, CYP2D6 inhibitor strength, and CYP2D6 metabolizer status. See prescribing information for details. Concomitant use may increase aripiprazole exposure and risk for side effects. Aripiprazole is a CYP3A and CYP2D6 substrate; bicalutamide is a weak CYP3A inhibitor.
Aspirin, ASA; Oxycodone: (Moderate) Consider a reduced dose of oxycodone with frequent monitoring for respiratory depression and sedation if concurrent use of bicalutamide is necessary. If bicalutamide is discontinued, consider increasing the oxycodone dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oxycodone is a CYP3A4 substrate, and coadministration with a weak inhibitor like bicalutamide can increase oxycodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of oxycodone. If bicalutamide is discontinued, oxycodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to oxycodone.
Benzhydrocodone; Acetaminophen: (Moderate) Concurrent use of benzhydrocodone with bicalutamide may increase the risk of increased opioid-related adverse reactions, such as fatal respiratory depression. Consider a dose reduction of benzhydrocodone until stable drug effects are achieved. Monitor patients for respiratory depression and sedation at frequent intervals. Discontinuation of bicalutamide in a patient taking benzhydrocodone may decrease hydrocodone plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to opioid agonists. If bicalutamide is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Benzhydrocodone is a prodrug for hydrocodone. Hydrocodone is a substrate for CYP3A4. Bicalutamide is a weak inhibitor of CYP3A4.
Bupivacaine; Lidocaine: (Moderate) Monitor for lidocaine toxicity if coadministration with bicalutamide is necessary as concurrent use may increase lidocaine exposure. Lidocaine is a CYP3A4 substrate and bicalutamide is a weak CYP3A4 inhibitor.
Carbamazepine: (Major) Monitor for increased carbamazepine-related adverse reactions if coadministered with bicalutamide. Taking these drugs together may increase carbamazepine plasma concentrations, potentially resulting in adverse events. Bicalutamide is a weak CYP3A4 inhibitor; carbamazepine is a substrate of CYP3A4 with a narrow therapeutic index.
Celecoxib; Tramadol: (Moderate) Consider a tramadol dosage reduction until stable drug effects are achieved if coadministration with bicalutamide is necessary. Closely monitor for seizures, serotonin syndrome, and signs of sedation and respiratory depression. Respiratory depression from increased tramadol exposure may be fatal. Concurrent use of bicalutamide, a weak CYP3A4 inhibitor, may increase tramadol exposure and result in greater CYP2D6 metabolism thereby increasing exposure to the active metabolite M1, which is a more potent mu-opioid agonist.
Chlorpheniramine; Dihydrocodeine; Phenylephrine: (Moderate) Concomitant use of dihydrocodeine with bicalutamide may increase dihydrocodeine plasma concentrations, resulting in greater metabolism by CYP2D6, increased dihydromorphine concentrations, and prolonged opioid adverse reactions, including hypotension, respiratory depression, profound sedation, coma, and death. If coadministration is necessary, monitor patients closely at frequent intervals and consider a dosage reduction of dihydrocodeine until stable drug effects are achieved. Discontinuation of bicalutamide could decrease dihydrocodeine plasma concentrations, decrease opioid efficacy, and potentially lead to a withdrawal syndrome in those with physical dependence to dihydrocodeine. If bicalutamide is discontinued, monitor the patient carefully and consider increasing the opioid dosage if appropriate. Bicalutamide is a weak inhibitor of CYP3A4, an isoenzyme partially responsible for the metabolism of dihydrocodeine.
Chlorpheniramine; Hydrocodone: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of bicalutamide is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like bicalutamide can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If bicalutamide is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
Cisapride: (Moderate) Use caution when administering bicalutamide with cisapride. Taking these drugs together may increase cisapride plasma concentrations, potentially resulting in adverse events. Bicalutamide is a weak CYP3A4 inhibitor; cisapride is a substrate of CYP3A4 with a narrow therapeutic index.
Clozapine: (Moderate) Consider a clozapine dose reduction if coadministered with bicalutamide and monitor for adverse reactions. If bicalutamide is discontinued, monitor for lack of clozapine effect and increase dose if necessary. A clinically relevant increase in the plasma concentration of clozapine may occur during concurrent use. Clozapine is partially metabolized by CYP3A4. Bicalutamide is a weak CYP3A4 inhibitor.
Cyclosporine: (Moderate) Closely monitor cyclosporine whole blood trough concentrations as appropriate and watch for cyclosporine-related adverse reactions if coadministration with bicalutamide is necessary. The dose of cyclosporine may need to be adjusted. Concurrent use may increase cyclosporine exposure causing an increased risk for cyclosporine-related adverse events. Cyclosporine is a CYP3A4 substrate and bicalutamide is a weak CYP3A4 inhibitor.
Diazepam: (Moderate) Monitor for an increase in diazepam-related adverse reactions, including sedation and respiratory depression, if coadministration with bicalutamide is necessary. Concurrent use may increase diazepam exposure. Diazepam is a CYP3A4 substrate and bicalutamide is a CYP3A4 inhibitor.
Disopyramide: (Moderate) Monitor for an increase in disopyramide-related adverse reactions if coadministration with bicalutamide is necessary as concurrent use may increase disopyramide exposure. Disopyramide is a CYP3A4 substrate and bicalutamide is a weak CYP3A4 inhibitor. Although specific drug interaction studies have not been done for disopyramide, cases of life-threatening interactions have been reported when disopyramide was coadministered with moderate and strong CYP3A4 inhibitors.
Dofetilide: (Moderate) Monitor for an increase in dofetilide-related adverse reactions, including QT prolongation, if coadministration with bicalutamide is necessary as concurrent use may increase dofetilide exposure. Bicalutamide is a weak CYP3A inhibitor. Dofetilide is a minor CYP3A substrate; however, because there is a linear relationship between dofetilide plasma concentration and QTc, concomitant administration of CYP3A inhibitors may increase the risk of arrhythmia (torsade de pointes).
Eliglustat: (Major) In poor CYP2D6 metabolizers (PMs), coadministration of bicalutamide and eliglustat is not recommended. In extensive CYP2D6 metabolizers (EM) with mild hepatic impairment, coadministration of bicalutamide and eliglustat requires dosage reduction of eliglustat to 84 mg PO once daily. Bicalutamide is a weak CYP3A4 inhibitor; eliglustat is a CYP3A and CYP2D6 substrate. Coadministration with CYP3A4 inhibitors, such as bicalutamide, may increase eliglustat exposure and the risk of serious adverse events (e.g., QT prolongation and cardiac arrhythmias).
Felodipine: (Moderate) Concurrent use of felodipine and bicalutamide should be approached with caution and conservative dosing of felodipine due to the potential for significant increases in felodipine exposure. Monitor for evidence of increased felodipine effects including decreased blood pressure and increased heart rate. Felodipine is a sensitive CYP3A4 substrate and bicalutamide is a weak CYP3A4 inhibitor. Concurrent use of another weak CYP3A4 inhibitor increased felodipine AUC and Cmax by approximately 50%.
Fentanyl: (Moderate) Consider a reduced dose of fentanyl with frequent monitoring for respiratory depression and sedation if concurrent use of bicalutamide is necessary. If bicalutamide is discontinued, consider increasing the fentanyl dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Fentanyl is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like bicalutamide can increase fentanyl exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of fentanyl. If bicalutamide is discontinued, fentanyl plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to fentanyl.
Finerenone: (Moderate) Monitor serum potassium during initiation or dose adjustment of either finerenone or bicalutamide; a finerenone dosage reduction may be necessary. Concomitant use may increase finerenone exposure and the risk of hyperkalemia. Finerenone is a CYP3A substrate and bicalutamide is a weak CYP3A inhibitor. Coadministration with another weak CYP3A inhibitor increased overall exposure to finerenone by 21%.
Flibanserin: (Moderate) The concomitant use of flibanserin and multiple weak CYP3A4 inhibitors, including bicalutamide, may increase flibanserin concentrations, which may increase the risk of flibanserin-induced adverse reactions. Therefore, patients should be monitored for hypotension, syncope, somnolence, or other adverse reactions, and the potential outcomes of combination therapy with multiple weak CYP3A4 inhibitors and flibanserin should be discussed with the patient.
Flurazepam: (Moderate) Monitor for an increase in flurazepam-related adverse reactions, including sedation and respiratory depression, if coadministration with bicalutamide is necessary. Concurrent use may increase flurazepam exposure. Flurazepam is a CYP3A4 substrate and bicalutamide is a CYP3A4 inhibitor.
Grapefruit juice: (Moderate) Substances that are potent inhibitors of CYP3A4 activity decrease the metabolism of bicalutamide and increase bicalutamide concentrations. This increase may be clinically relevant as adverse reactions to bicalutamide are related to dose and exposure; therefore caution should be used when administering CYP3A4 inhibitors, such as grapefruit juice. with bicalutamide.
Guaifenesin; Hydrocodone: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of bicalutamide is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like bicalutamide can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If bicalutamide is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
Homatropine; Hydrocodone: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of bicalutamide is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like bicalutamide can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If bicalutamide is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
Hydrocodone: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of bicalutamide is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like bicalutamide can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If bicalutamide is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
Hydrocodone; Ibuprofen: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of bicalutamide is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like bicalutamide can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If bicalutamide is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
Hydrocodone; Pseudoephedrine: (Moderate) Consider a reduced dose of hydrocodone with frequent monitoring for respiratory depression and sedation if concurrent use of bicalutamide is necessary. It is recommended to avoid this combination when hydrocodone is being used for cough. Hydrocodone is a CYP3A4 substrate, and coadministration with CYP3A4 inhibitors like bicalutamide can increase hydrocodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of hydrocodone. These effects could be more pronounced in patients also receiving a CYP2D6 inhibitor. If bicalutamide is discontinued, hydrocodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to hydrocodone.
Ibuprofen; Oxycodone: (Moderate) Consider a reduced dose of oxycodone with frequent monitoring for respiratory depression and sedation if concurrent use of bicalutamide is necessary. If bicalutamide is discontinued, consider increasing the oxycodone dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oxycodone is a CYP3A4 substrate, and coadministration with a weak inhibitor like bicalutamide can increase oxycodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of oxycodone. If bicalutamide is discontinued, oxycodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to oxycodone.
Isradipine: (Minor) Monitor for an increase in isradipine-related adverse reactions including hypotension if coadministration with bicalutamide is necessary. Concomitant use may increase isradipine exposure. Isradipine is a CYP3A substrate and bicalutamide is a weak CYP3A inhibitor.
Ixabepilone: (Moderate) Monitor for ixabepilone toxicity and reduce the ixabepilone dose as needed if concurrent use of bicalutamide is necessary. Concomitant use may increase ixabepilone exposure and the risk of adverse reactions. Ixabepilone is a CYP3A substrate and bicalutamide is a weak CYP3A inhibitor.
Lemborexant: (Major) Limit the dose of lemborexant to a maximum of 5 mg PO once daily if coadministered with bicalutamide as concurrent use may increase lemborexant exposure and the risk of adverse effects. Lemborexant is a CYP3A4 substrate; bicalutamide is a weak CYP3A4 inhibitor. Coadministration of lemborexant with a weak CYP3A4 inhibitor is predicted to increase lemborexant exposure by less than 2-fold.
Lidocaine: (Moderate) Monitor for lidocaine toxicity if coadministration with bicalutamide is necessary as concurrent use may increase lidocaine exposure. Lidocaine is a CYP3A4 substrate and bicalutamide is a weak CYP3A4 inhibitor.
Lidocaine; Epinephrine: (Moderate) Monitor for lidocaine toxicity if coadministration with bicalutamide is necessary as concurrent use may increase lidocaine exposure. Lidocaine is a CYP3A4 substrate and bicalutamide is a weak CYP3A4 inhibitor.
Lidocaine; Prilocaine: (Moderate) Monitor for lidocaine toxicity if coadministration with bicalutamide is necessary as concurrent use may increase lidocaine exposure. Lidocaine is a CYP3A4 substrate and bicalutamide is a weak CYP3A4 inhibitor.
Lomitapide: (Major) Concomitant use of lomitapide and bicalutamide may significantly increase the serum concentration of lomitapide. Therefore, the lomitapide dose should not exceed 30 mg/day PO during concurrent use. Bicalutamide is a weak CYP3A4 inhibitor; the exposure to lomitapide is increased by approximately 2-fold in the presence of weak CYP3A4 inhibitors.
Lonafarnib: (Major) Avoid coadministration of lonafarnib and bicalutamide; concurrent use may increase the exposure of lonafarnib and the risk of adverse effects. If coadministration is unavoidable, reduce to or continue lonafarnib at a dosage of 115 mg/m2 and closely monitor patients for lonafarnib-related adverse reactions. Resume previous lonafarnib dosage 14 days after discontinuing bicalutamide. Lonafarnib is a sensitive CYP3A4 substrate and bicalutamide is a weak CYP3A4 inhibitor.
Mefloquine: (Moderate) Use mefloquine with caution if coadministration with bicalutamide is necessary as concurrent use may increase mefloquine exposure and mefloquine-related adverse events. Mefloquine is a substrate of CYP3A4 and bicalutamide is a weak CYP3A4 inhibitor.
Methadone: (Moderate) Consider a reduced dose of methadone with frequent monitoring for respiratory depression and sedation if concurrent use of bicalutamide is necessary. If bicalutamide is discontinued, methadone plasma concentrations can decrease resulting in reduced efficacy and potential withdrawal syndrome in a patient who has developed physical dependence to methadone. Methadone is a substrate of CYP3A4, CYP2B6, CYP2C19, CYP2C9, and CYP2D6; bicalutamide is a weak CYP3A4 enzyme inhibitor. Concomitant use with bicalutamide can increase methadone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of methadone.
Midazolam: (Moderate) Use caution when midazolam is coadministered with bicalutamide. Concurrent use may increase midazolam exposure leading to prolonged sedation. Midazolam is a sensitive CYP3A4 substrate and bicalutamide is a weak CYP3A4 inhibitor. Clinical studies have shown that bicalutamide may increase mean midazolam exposure by 1.5-fold for Cmax and 1.9-fold for AUC.
Nanoparticle Albumin-Bound Sirolimus: (Major) Reduce the nab-sirolimus dose to 56 mg/m2 during concomitant use of bicalutamide. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a CYP3A substrate and bicalutamide is a weak CYP3A inhibitor.
Nimodipine: (Moderate) Monitor blood pressure and reduce the dose of nimodipine as clinically appropriate if coadministration with bicalutamide is necessary. Concurrent use may increase nimodipine exposure. Nimodipine is a CYP3A4 substrate and bicalutamide is a weak CYP3A4 inhibitor.
Nisoldipine: (Major) Avoid coadministration of nisoldipine with bicalutamide due to increased plasma concentrations of nisoldipine. If coadministration is unavoidable, monitor blood pressure closely during concurrent use of these medications. Nisoldipine is a CYP3A4 substrate and bicalutamide is a weak CYP3A4 inhibitor.
Oxycodone: (Moderate) Consider a reduced dose of oxycodone with frequent monitoring for respiratory depression and sedation if concurrent use of bicalutamide is necessary. If bicalutamide is discontinued, consider increasing the oxycodone dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Oxycodone is a CYP3A4 substrate, and coadministration with a weak inhibitor like bicalutamide can increase oxycodone exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of oxycodone. If bicalutamide is discontinued, oxycodone plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to oxycodone.
Pimozide: (Major) Concurrent use of pimozide and bicalutamide should be avoided. Coadministration may result in elevated pimozide concentrations resulting in QT prolongation, ventricular arrhythmias, and sudden death. Pimozide is metabolized primarily through CYP3A4, and bicalutamide is a weak CYP3A4 inhibitor.
Propafenone: (Moderate) Monitor for increased propafenone toxicity if coadministered with bicalutamide; concurrent use may increase propafenone exposure and therefore increase the risk of proarrhythmias. Avoid simultaneous use of propafenone and bicalutamide with a CYP2D6 inhibitor or in patients with CYP2D6 deficiency. Propafenone is a CYP3A4 and CYP2D6 substrate; bicalutamide is a weak CYP3A4 inhibitor.
Sirolimus: (Moderate) Monitor sirolimus concentrations and adjust sirolimus dosage as appropriate during concomitant use of bicalutamide. Coadministration may increase sirolimus concentrations and increase the risk for sirolimus-related adverse effects. Sirolimus is a CYP3A substrate and bicalutamide is a weak CYP3A inhibitor.
Sufentanil: (Moderate) Because the dose of the sufentanil sublingual tablets cannot be titrated, consider an alternate opiate if bicalutamide must be administered. Consider a reduced dose of sufentanil injection with frequent monitoring for respiratory depression and sedation if concurrent use of bicalutamide is necessary. If bicalutamide is discontinued, consider increasing the sufentanil injection dose until stable drug effects are achieved and monitor for evidence of opioid withdrawal. Sufentanil is a CYP3A4 substrate, and coadministration with a weak CYP3A4 inhibitor like bicalutamide can increase sufentanil exposure resulting in increased or prolonged opioid effects including fatal respiratory depression, particularly when an inhibitor is added to a stable dose of sufentanil. If bicalutamide is discontinued, sufentanil plasma concentrations will decrease resulting in reduced efficacy of the opioid and potential withdrawal syndrome in a patient who has developed physical dependence to sufentanil.
Tacrolimus: (Moderate) Monitor tacrolimus serum concentrations as appropriate and watch for tacrolimus-related adverse reactions if coadministration with bicalutamide is necessary. The dose of tacrolimus may need to be reduced. Tacrolimus is a sensitive CYP3A4 substrate with a narrow therapeutic range; bicalutamide is a weak CYP3A4 inhibitor.
Tramadol: (Moderate) Consider a tramadol dosage reduction until stable drug effects are achieved if coadministration with bicalutamide is necessary. Closely monitor for seizures, serotonin syndrome, and signs of sedation and respiratory depression. Respiratory depression from increased tramadol exposure may be fatal. Concurrent use of bicalutamide, a weak CYP3A4 inhibitor, may increase tramadol exposure and result in greater CYP2D6 metabolism thereby increasing exposure to the active metabolite M1, which is a more potent mu-opioid agonist.
Tramadol; Acetaminophen: (Moderate) Consider a tramadol dosage reduction until stable drug effects are achieved if coadministration with bicalutamide is necessary. Closely monitor for seizures, serotonin syndrome, and signs of sedation and respiratory depression. Respiratory depression from increased tramadol exposure may be fatal. Concurrent use of bicalutamide, a weak CYP3A4 inhibitor, may increase tramadol exposure and result in greater CYP2D6 metabolism thereby increasing exposure to the active metabolite M1, which is a more potent mu-opioid agonist.
Triazolam: (Moderate) Monitor for signs of triazolam toxicity during coadministration with bicalutamide and consider appropriate dose reduction of triazolam if clinically indicated. Coadministration may increase triazolam exposure. Triazolam is a sensitive CYP3A substrate and bicalutamide is a weak CYP3A inhibitor.
Ubrogepant: (Major) Limit the initial and second dose of ubrogepant to 50 mg if coadministered with bicalutamide. Concurrent use may increase ubrogepant exposure and the risk of adverse effects. Ubrogepant is a CYP3A4 substrate; bicalutamide is a weak CYP3A4 inhibitor.
Vinorelbine: (Moderate) Monitor for an earlier onset and/or increased severity of vinorelbine-related adverse reactions, including constipation and peripheral neuropathy, if coadministration with bicalutamide is necessary. Vinorelbine is a CYP3A4 substrate and bicalutamide is a weak CYP3A4 inhibitor.
Warfarin: (Moderate) Closely monitor the PT/INR if coadministration of warfarin with bicalutamide is necessary as concurrent use may increase the exposure of warfarin leading to increased bleeding risk. In vitro protein-binding studies have shown that bicalutamide can displace coumarin anticoagulants from binding sites. There have been reports of excessive prolongation of the PT/INR days to weeks after the introduction of bicalutamide in patients who were previously stable on coumarin anticoagulants. Some patients had serious bleeding including intracranial, retroperitoneal, and gastrointestinal requiring blood transfusion and/or administration of vitamin K. Additionally, bicalutamide is a weak CYP3A4 inhibitor and the R-enantiomer of warfarin is a CYP3A4 substrate; the S-enantiomer of warfarin exhibits 2 to 5 times more anticoagulant activity than the R-enantiomer, but the R-enantiomer generally has a slower clearance.

Bicalutamide/Casodex Oral Tab: 50mg

50 mg/day PO.

50 mg/day PO.

Safety and efficacy have not been established.

Safety and efficacy have not been established.

Bicalutamide is a nonsteroidal androgen receptor inhibitor. It competitively inhibits the action of androgens by binding to cytosol androgen receptors in the target tissue. When bicalutamide is combined with LHRH analog therapy, the suppression of serum testosterone induced by the LHRH analog is not affected; however, in clinical trials with bicalutamide as a single agent for prostate cancer, rises in serum testosterone and estradiol have been noted. In patients who have been treated with bicalutamide and an LHRH agonist, and who discontinue bicalutamide therapy due to progressive advanced prostate cancer, a reduction in PSA and/or clinical improvement (antiandrogen withdrawal phenomenon) may be observed.

Bicalutamide is administered orally; it is 96% protein-bound. Bicalutamide undergoes stereospecific metabolism. The S isomer (inactive) is primarily metabolized by glucuronidation. The active R isomer also undergoes glucuronidation but is predominantly oxidized to an inactive metabolite followed by glucuronidation. The S-enantiomer is rapidly cleared relative to the R-enantiomer, with the R-enantiomer accounting for about 99% of total steady-state plasma concentrations. Both the parent and metabolite glucuronides are eliminated in the urine and feces. The half-life of the R-enantiomer is roughly 5.8 days (+/- 2.29 days) for adults without liver disease. The mean apparent oral clearance is 0.32 L/hour (+/- 0.103 L/hour).
 
Affected cytochrome P450 isoenzymes: CYP3A4, CYP2C9, CYP2C19, CYP2D6
R-bicalutamide is a weak CYP3A4 inhibitor in vitro; it has lesser inhibitory effects on CYP2C9, CYP2C19, and CYP2D6.

The absolute bioavailability of bicalutamide is not known despite being well-absorbed orally. The single-dose peak concentration of bicalutamide is 0.768 mcg/mL (+/- 0.178 mcg/mL) in healthy males and the single-dose time to peak concentration is 31.3 hours (+/- 14.6 hours). In patients with prostate cancer, the concentration at steady-state is 8.939 mcg/mL (+/- 3.504 mcg/mL). Coadministration of bicalutamide with food has no clinically significant effect on the rate or extent of absorption.

Bicalutamide is not indicated for use in women; therefore, it should not be used in women who are breast-feeding. It is not known whether bicalutamide is present in human milk, although many drugs are excreted in human milk.