Flutamide
Active form: Hydroxyflutamide.
JFDA label: FLUTAN TAB
- Hepatic injury:
Mechanism of Action
Antagonist of Androgen receptor — Androgen Receptor antagonist
| Target | Action | Gene / class |
|---|---|---|
| Androgen receptor efficacy | ANTAGONIST | AR |
Indications
Approved
- Prostate cancer
Contraindications
Source: Lexicomp
- Hypersensitivity to flutamide or any component of the formulation Absolute
- severe hepatic impairment (evaluate baseline hepatic enzymes prior to treatment) Absolute
Adverse Reactions
Cardiac disorders (2)
Common Edema · hypertension
Nervous system disorders (8)
Common Anxiety · confusion · depression · dizziness · drowsiness · headache · insomnia · nervousness
Hepatobiliary disorders (1)
Very Common Increased serum AST (transient; mild)
Renal and urinary disorders (4)
Very Common breast tenderness · cystitis · Impotence
Common Hematuria
Blood and lymphatic system disorders (5)
Very Common Rectal hemorrhage · tumor flare
Common Anemia · leukopenia · thrombocytopenia
Metabolism and nutrition disorders (5)
Very Common decreased libido · galactorrhea · Hot flash · increased lactate dehydrogenase (transient; mild)
Common Gynecomastia
Gastrointestinal disorders (9)
Very Common Diarrhea · vomiting
Common anorexia · constipation · dyspepsia · gastric distress · increased appetite · Nausea · proctitis
Skin and subcutaneous tissue disorders (3)
Common ecchymoses · pruritus · Skin rash
Musculoskeletal and connective tissue disorders (1)
Common Weakness
Infections and infestations (1)
Common Herpes zoster
Dosing
Source: Lexicomp
Warnings & Precautions
Source: Lexicomp
Gynecomastia
Gynecomastia may occur in patients receiving flutamide in combination with medical castration.
Hepatic failure
[U.S. Boxed Warning]: Hospitalization and death (rare) due to liver failure have been reported in patients taking flutamide. Elevated serum transaminase levels, jaundice, hepatic encephalopathy, and acute hepatic failure have been reported. Hepatotoxicity was reversible after discontinuation in some cases. In about 50% of the cases, the onset of hepatotoxicity was within the first 3 months of treatment. Monitor serum transaminase levels at baseline, monthly for 4 months, and periodically thereafter. Also obtain liver function tests at the first symptoms suggestive of liver dysfunction (nausea, vomiting, abdominal pain, fatigue, anorexia, “flu-like” symptoms, hyperbilirubinuria, jaundice, or right upper quadrant tenderness). Use is not recommended in patients with ALT values greater than 2 times ULN; discontinue use immediately in patients with jaundice or if ALT rises above 2 times ULN. Use is contraindicated in patients with severe hepatic impairment. Disease-related concerns:
Cardiovascular disease
Androgen-deprivation therapy may increase the risk for cardiovascular disease (Levine, 2010).
Hemoglobin M disease
Patients with hemoglobin M disease are at risk of toxicities associated with aniline exposure, including methemoglobinemia, hemolytic anemia, and cholestatic jaundice; monitor methemoglobin levels. Concurrent drug therapy issues:
Drug-drug interactions
Potentially significant interactions may exist, requiring dose or frequency adjustment, additional monitoring, and/or selection of alternative therapy. Consult drug interactions database for more detailed information. Special populations:
Glucose-6 phosphate dehydrogenase deficiency
Patients with glucose-6 phosphate dehydrogenase deficiency are at risk of toxicities associated with aniline exposure, including methemoglobinemia, hemolytic anemia, and cholestatic jaundice; monitor methemoglobin levels.
Smokers
Patients who smoke are at risk of toxicities associated with aniline exposure, including methemoglobinemia, hemolytic anemia, and cholestatic jaundice; monitor methemoglobin levels.
Women
Not indicated for use in women and should not be used in women, particularly for nonserious or nonlife-threatening conditions.
Pregnancy & Lactation
Pregnancy
Adverse events have been observed in animal reproduction studies. May cause fetal harm if administered in pregnancy. Flutamide is not indicated for use in women.
Lactation
According to the manufacturer, this product is not indicated for use in women. Information related to use in nursing women has not been located.
Monitoring
| Clinical pearl | Serum transaminases (at baseline, monthly for 4 months, and periodically thereafter); monitor liver function tests at the first sign or symptom of liver dysfunction (eg, nausea, vomiting, abdominal pain, fatigue, anorexia, flu-like symptoms, hyperbilirubinuria, jaundice, or right upper quadrant tenderness); monitor prostate specific antigen (PSA) |
|---|
Chemistry & Properties
| Formula | C11H11F3N2O3 |
|---|---|
| Molecular weight | 276.21 g/mol |
| IUPAC name | 2-methyl-N-[4-nitro-3-(trifluoromethyl)phenyl]propanamide |
| CAS | 13311-84-7 |
| PubChem CID | 3397 |
| InChIKey | MKXKFYHWDHIYRV-UHFFFAOYSA-N |
| logP | 3.21 (XLogP 3.3) |
| Polar surface area | 72.24 Ų |
| H-bond acceptors / donors | 3 / 1 |
| Drug-likeness (QED) | 0.68 |
| Lipinski violations | 0 |
SMILES
CC(C)C(=O)Nc1ccc([N+](=O)[O-])c(C(F)(F)F)c1Biology & Pharmacokinetics
Pharmacokinetics
| BBB penetrant | No |
|---|
Enzyme interactions
| Enzyme | Role | Detail |
|---|---|---|
| CYP1A2 | Inhibitor | — |
| CYP1A2 | Substrate | — |
| CYP2C19 | Inhibitor | — |
| CYP2C19 | Substrate | — |
| CYP2C8 | Inhibitor | — |
| CYP2C9 | Substrate | — |
| CYP3A4 | Inhibitor | — |
| CYP3A4 | Substrate | — |
Receptor binding (top 1)
| Target | Action | Affinity |
|---|---|---|
| Androgen receptor (AR) | Antagonist | pKi 5.4 |
Transporters
BCRP (Inhibitor)BCRP (Inhibitor)BSEP (Inhibitor)BSEP (Inhibitor)MRP1 (Inhibitor)MRP2 (Inhibitor)MRP3 (Inhibitor)MRP4 (Inhibitor)NTCP (Inhibitor)OATP1B1 (Inhibitor)OATP1B1 (Inhibitor)OATP1B3 (Inhibitor)OATP1B3 (Inhibitor)OATP2B1 (Inhibitor)OCT1 (Inhibitor)P-gp (Inhibitor)P-gp (Substrate)
Drug–drug interactions (100+, DDInter)
| Interacting drug | Severity | Management |
|---|---|---|
| Amiodarone | major | |
| Amisulpride | major | |
| Anagrelide | major | |
| Arsenic trioxide | major | |
| Bedaquiline | major | |
| Bepridil | major | |
| Cabozantinib | major | |
| Ceritinib | major | |
| Cisapride | major | |
| Citalopram | major | |
| Clozapine | major | |
| Crizotinib | major | |
| Disopyramide | major | |
| Dofetilide | major | |
| Dolasetron | major | |
| Dronedarone | major | |
| Droperidol | major | |
| Escitalopram | major | |
| Fingolimod | major | |
| Gatifloxacin | major | |
| Grepafloxacin | major | |
| Halofantrine | major | |
| Haloperidol | major | |
| Ibutilide | major | |
| Iloperidone | major | |
| Ivabradine | major | |
| Ivosidenib | major | |
| Lefamulin | major | |
| Leflunomide | major | |
| Levacetylmethadol | major | |
| Lomitapide | major | |
| Lumefantrine | major | |
| Macimorelin | major | |
| Mesoridazine | major | |
| Methadone | major | |
| Mifepristone | major | |
| Mipomersen | major | |
| Moxifloxacin | major | |
| Nilotinib | major | |
| Nitrous acid | major |
Showing 40 of 100+.
Registered Products (3)
| Brand | Form / strength | Pack | Agent | Citizen (JOD) |
|---|---|---|---|---|
| FLUTAN TAB | Tablet 250 mg | 20 tab pack varies | Khoury Drug Store | 12.690 |
| Curestat capsule | Capsule 250 mg | 20 cap | The Arab Pharmaceutical Manufacturing PSC/Salt | 19.780 |
| FLUTAN TAB | Tablet 250 mg | 100 tab pack varies | Khoury Drug Store | 47.480 |