Flutamide Side Effects

Not all side effects for flutamide may be reported. You should always consult a doctor or healthcare professional for medical advice. Side effects can be reported to the FDA here.

For the Consumer

Applies to flutamide: oral capsule, oral tablet

In addition to its needed effects, some unwanted effects may be caused by flutamide. In the event that any of these side effects do occur, they may require medical attention.

You should check with your doctor immediately if any of these side effects occur when taking flutamide:

More common
  • Black, tarry stools
  • bloody or cloudy urine
  • continuing diarrhea
  • continuing stomach pain
  • difficult, burning, or painful urination
  • frequent urge to urinate
  • pale skin
  • troubled breathing with exertion
  • unusual bleeding or bruising
  • unusual tiredness or weakness
Less common
  • Blurred vision
  • chest pain
  • chills
  • cough
  • difficulty with breathing
  • dizziness
  • drowsiness
  • fever
  • headache
  • nervousness
  • pounding in the ears
  • shortness of breath
  • slow or fast heartbeat
  • sore throat
  • sores, ulcers, or white spots on the lips or in the mouth
  • swelling
  • swollen glands
Rare
  • Abdominal or stomach pain
  • clay-colored stools
  • dark urine
  • general tiredness and weakness
  • itching
  • light-colored stools
  • loss of appetite
  • nausea and vomiting
  • rash
  • tumor
  • unpleasant breath odor
  • upper right abdominal pain
  • vomiting of blood
  • yellow eyes and skin
Incidence not known
  • Back, leg, or stomach pains
  • bleeding gums
  • blistering, peeling, or loosening of the skin
  • bluish-colored lips, fingernails, or palms
  • discoloration of the urine
  • dizziness or lightheadedness
  • flushing or redness of the skin
  • general body swelling
  • headache
  • itching
  • joint or muscle pain
  • nosebleeds
  • rapid heart rate
  • red irritated eyes
  • red skin lesions, often with a purple center
  • unusually warm skin

If any of the following symptoms of overdose occur while taking flutamide, get emergency help immediately:

Symptoms of overdose
  • Goosebumps
  • shakiness and unsteady walk
  • tearing of the eyes
  • unsteadiness, trembling, or other problems with muscle control or coordination
  • weight loss

Some of the side effects that can occur with flutamide may not need medical attention. As your body adjusts to the medicine during treatment these side effects may go away. Your health care professional may also be able to tell you about ways to reduce or prevent some of these side effects. If any of the following side effects continue, are bothersome or if you have any questions about them, check with your health care professional:

More common
  • Decreased interest in sexual intercourse
  • diarrhea
  • feeling of warmth
  • inability to have or keep an erection
  • indigestion
  • loss in sexual ability, desire, drive, or performance
  • passing of gas
  • redness of the face, neck, arms and occasionally, upper chest
  • stomach pain, fullness, or discomfort
  • sudden sweating
  • swelling of the breasts or breast soreness in both females and males
Less common
  • Depression
  • drowsiness
  • fear or nervousness
  • mood or mental changes

For Healthcare Professionals

Applies to flutamide: oral capsule

General

In general, flutamide has been used concomitantly with LHRH agonists or after bilateral orchiectomy. Therefore, little data are available on the side effects of flutamide alone.[Ref]

Hepatic

Nineteen cases of severe flutamide related hepatotoxicity were reported by the FDA in 1993. The flutamide related hepatitis developed 56 to 80 days after the beginning of therapy and was mainly cytolytic. Four of the cases involved massive hepatic necrosis with fatal outcomes. The mechanism of action was believed to be direct hepatotoxicity.

In a study of 1,091 patients with prostate cancer treated with flutamide and an LHRH agonist, four patients (0.36%) developed severe hepatotoxicity in the first four weeks of therapy. Serum aminotransferases increased more than four times normal values. Alkaline phosphatase increased more than six times normal values in one patient. Total bilirubin was elevated in two patients. Only two patients developed clinical manifestations, including fatigue, anorexia, weight loss, nausea, and vomiting. None of the remaining 1,089 patients had significant elevations in liver function tests although transient, mild elevations in AST and ALT occasionally occurred.

In most cases, discontinuation of flutamide results in resolution of symptoms.

A case of fatal liver complications has been reported where the drug was prescribed for an 18 year old woman for the treatment of minor acne and hirsutism. The risk of lethal hepatic complications makes the risk-benefit ratio unacceptable when flutamide is being considered to treat disorders such as polycystic ovaries, and especially for benign complaints such as alopecia, hirsutism, and acne.[Ref]

Hepatic side effects have included elevations in serum transaminases as well as cases of cholestatic jaundice, hepatic necrosis, hepatic encephalopathy, and fatal hepatotoxicity.[Ref]

Hematologic

Hematologic side effects have included anemia (6%), leukopenia (3%), and thrombocytopenia (1%). Flutamide has also been implicated in cases of methemoglobinemia, sulphemoglobinemia and neutropenia. In addition, eosinophilia has been reported in association with some cases of hepatotoxicity.[Ref]

Nervous system

Nervous system side effects have been reported in less than 1% of patients and include drowsiness, dizziness, sedation, and confusion.[Ref]

Renal

Renal side effects including renal failure (in association with severe hepatotoxicity) have been reported.[Ref]

Cardiovascular

Cardiovascular side effects reported include hypertension (1%), thromboembolism, and edema.[Ref]

Dermatologic

Pseudoporphyria (blisters, increased skin fragility, and erosions in sun-exposed areas) was reported in a 68-year-old man being treated for prostate cancer with appropriate doses of flutamide and goserelin. The patient presented with skin fragility and blisters on the back of the hands. After replacing the flutamide with bicalutamide, the lesions healed.[Ref]

Dermatologic side effects including rash (3%), alopecia, sweating, and cases of photosensitivity/photoallergy have been reported. One case of flutamide-induced pseudoporphyria has also been reported.[Ref]

Endocrine

Endocrine side effects including hot flashes (29% to 63%), gynecomastia (up to 19%), fever, and breast tenderness (7%) have been reported.[Ref]

Gastrointestinal

Two female patients receiving flutamide for the treatment of bulimia nervosa noted decreased symptoms within a week after initiation of therapy. Both patients relapsed after the drug was later withdrawn.[Ref]

Gastrointestinal side effects including mucositis, diarrhea, nausea, vomiting, abdominal pain, anorexia, and either weight loss or gain have been reported.[Ref]

Musculoskeletal

Musculoskeletal side effects including muscle cramps in up to 15% of patients have been reported.[Ref]

Psychiatric

Psychiatric side effects including depression, anxiety, and nervousness have been reported. One case report of mania has also been reported.[Ref]

Genitourinary

Genitourinary side effects including impotence and loss of libido have been reported.[Ref]

Other

Several studies have described a flutamide withdrawal syndrome in which significant reductions in prostate-specific antigen (PSA) levels are noted following the discontinuation of flutamide therapy in patients with hormone-refractory prostate cancer.

Several studies have evaluated the effect of concurrent discontinuation of flutamide and initiation of aminoglutethimide therapy in patients with hormone-refractory prostate cancer. In one study, serum PSA levels declined by more than 80% for more than four weeks in 14 out of 29 (48%) patients. Clinical improvement was also noted. Some authors propose prolonged flutamide therapy may result in the selective proliferation of cancer cell lines with androgen receptors which recognize hydroxyflutamide as an androgenic agonist. Additional research is needed to fully evaluate this phenomenon.[Ref]

Other side effects have included flutamide withdrawal syndrome.[Ref]

Respiratory

Respiratory side effects including one case of pneumonitis have been reported.[Ref]

References

1. "Multum Information Services, Inc. Expert Review Panel"

2. Moghetti P, Castello R, Negri C, Tosi F, Magnani CM, Fontanarosa MC, Armanini D, Muggeo M "Flutamide in the treatment of hirsutism: long-term clinical effects, endocrine changes, and androgen receptor behavior." Fertil Steril 64 (1995): 511-7

3. Hart W, Stricker BH "Flutamide and hepatitis ." Ann Intern Med 110 (1989): 943-4

4. Wallace C, Lalor EA, Chik CL "Hepatotoxicity complicating flutamide treatment of hirsutism." Ann Intern Med 119 (1993): 1150

5. Crownover RL, Holland J, Chen A, Krieg R, Young BK, Roach M, Fu KK "Flutamide-induced liver toxicity including fatal hepatic necrosis." Int J Radiat Oncol Biol Phys 34 (1996): 911-5

6. Moller S, Iversen P, Franzmann MB, Mller S "Flutamide-induced liver failure." J Hepatol 10 (1990): 346-9

7. Wysowski DK, Fourcroy JL "Hepatotoxicity complicating flutamide treatment of hirsutism - reply." Ann Intern Med 119 (1993): 1150

8. Kosar Y, Sasmaz N, Oguz P, Kucukbas S "Hepatic insufficiency developing as a result of flutamide treatment." Am J Gastroenterol 90 (1995): 1027-8

9. Gomez J-L, Dupont A, Cusan L, et al "Incidence of liver toxicity associated with the use of flutamide in prostate cancer patients." Am J Med 92 (1992): 465-70

10. "Product Information. Eulexin (flutamide)." Schering Laboratories, Kenilworth, NJ.

11. Wysowski DK, Freiman JP, Tourtelot JB, Horton ML "Fatal and nonfatal hepatotoxicity associated with flutamide." Ann Intern Med 118 (1993): 860-4

12. Tyrrell CJ, Altwein JE, Klippel F, et al "A multicenter randomized trial comparing the luteinizing hormone- releasing hormone analogue goserelin acetate alone and with flutamide in the treatment of advanced prostate cancer. The InternationalProstate Cancer Study Group." J Urol 146 (1991): 1321-6

13. Dourakis SP, Alexopoulou AA, Hadziyannis SJ "Fulminant hepatitis after flutamide treatment." J Hepatol 20 (1994): 350-3

14. Dankoff JS "Near fatal liver dysfunction secondary to administration of flutamide for prostate cancer." J Urol 148 (1992): 1914

15. Wysowski DK, Fourcroy JL "Flutamide hepatotoxicity." J Urol 155 (1996): 209-12

16. Podevin P, Biour M "Drug-induced ''allergic hepatitis''." Clin Rev Allergy Immunol 13 (1995): 223-44

17. Cicognani C, Malavolti M, Morsellilabate AM, Sama C, Barbara L "Flutamide-induced toxic hepatitis: potential utility of ursodeoxycholic acid administration in toxic hepatitis." Dig Dis Sci 41 (1996): 2219-21

18. Labrie F "Acute cholestatic hepatitis secondary to flutamide therapy - reply." Am J Med 96 (1994): 392-3

19. Rosenthal SA, Linstadt DE, Leibenhaut MH, Andras EJ, Brooks CP, Stickney DR, Chang GC, Wolkov HB, Gilbert RM "Flutamide-associated liver toxicity during treatment with total androgen suppression and radiation therapy for prostate cancer." Radiology 199 (1996): 451-5

20. Wysowski DK, Fourcroy JL "Flutamide hepatotoxicity." J Urol 155 (1996): 209-12

21. Osculati A, Castiglioni C "Fatal liver complications with flutamide." Lancet 367 (2006): 1140-1

22. Jackson SH, Barker SJ "Methemoglobinemia in a patient receiving flutamide." Anesthesiology 82 (1995): 1065-7

23. Kouides PA, Abboud CN, Fairbanks VF "Flutamide-induced cyanosis refractory to methylene blue therapy." Br J Haematol 94 (1996): 73-5

24. Schott AM, Vial T, Gozzo I, Chareyre S, Delmas PD "Flutamide-induced methemoglobinemia." DICP 25 (1991): 600-1

25. Mcdonnell ND, Livingston RB "Severe reversible neutropenia following treatment of prostate cancer with flutamide." J Urol 151 (1994): 1353-4

26. Ferrari P, Castagnetti G, Ferrari G, Baisi B, Dotti A "Combination treatment versus LHRH alone in advanced prostatic cancer." Urol Int 56 ( Suppl (1996): 13-7

27. Fujimoto M, Kikuchi K, Imakado S, Furue M "Photosensitive dermatitis induced by flutamide." Br J Dermatol 135 (1996): 496-7

28. Moraillon I, Jeanmougin M, Manciet JR, Revuz J, Bagot M "Photoallergic reaction induced by flutamide." Photodermatol Photoimmunol Photomed 8 (1991): 264-5

29. Borroni G, Brazzelli V, Baldini F, Borghini F, Gaviglio MR, Beltrami B, Nolli G "Flutamide-induced pseudoporphyria." Br J Dermatol 138 (1998): 711-2

30. Neri B, Bartalucci S, Pieri A, et al "Complete androgen blockade as treatment for advanced prostate cancer: clinical response and side-effects." Anticancer Res 9 (1989): 13-6

31. Narayan P, Trachtenberg J, Lepor H, Debruyne FMJ, Tewari A, Stone N, Das S, Jimenezcruz JF, Shearer R, Klingbert I, Schellhamme "A dose-response study of the effect of flutamide on benign prostatic hyperplasia: results of a multicenter study." Urology 47 (1996): 497-504

32. Bergman L, Eriksson E "Marked symptom reduction in two women with bulimia nervosa treated with the testosterone receptor antagonist flutamide." Acta Psychiatr Scand 94 (1996): 137-9

33. Rousseau L, Dupont A, Labrie F, Couture M "Sexuality changes in prostate cancer patients receiving antihormonal therapy combining the antiandrogen flutamide with medical (LHRH agonist) or surgical castration." Arch Sex Behav 17 (1988): 87-98

34. Kelly WK, Scher HI "Prostate specific antigen decline after antiandrogen withdrawal: the flutamide withdrawal syndrome." J Urol 149 (1993): 607-9

35. Sartor O, Cooper M, Weinberger M, et al. "Surprising activity of flutamide withdrawal, when combined with aminoglutethimide, in treatment of hormone-refractory prostate cancer." J Natl Cancer Inst 86 (1994): 222-7

36. Scher HI, Kelly WK "Flutamide withdrawal syndrome: its impact on clinical trials in hormone-refractory prostate cancer." J Clin Oncol 11 (1993): 1566-72

37. Bennett CL, Raisch DW, Sartor O "Pneumonitis associated with nonsteroidal antiandrogens: presumptive evidence of a class effect." Ann Intern Med 137 (2002): 625

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