Flutamide Side Effects

Brand Names: Eulexin

Please note - some side effects for Flutamide may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA at http://www.fda.gov/medwatch/ or 1-800-FDA-1088 (1-800-332-1088).

Side Effects of Flutamide - for the Consumer

Flutamide

All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome when using Flutamide:

Blood in the urine; breast growth; decreased sex drive or ability; diarrhea; hot flashes; inflamed prostate; nausea; rash; rectal bleeding; vomiting.

Severe allergic reactions (rash; hives; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); brown urine; flu-like symptoms; impotence; loss of appetite; muscle aches or soreness; nausea; severe diarrhea; stomach pain/tenderness; unusual tiredness; vomiting; yellowing of skin or eyes.

Flutamide Side Effects - for the Professional

Flutamide

Stage B2 -C Prostatic Carcinoma

 Treatment with Flutamide capsules and the goserelin acetate implant did not add substantially to the toxicity of radiation treatment alone. The following adverse experiences were reported during a multicenter clinical trial comparing Flutamide capsules + goserelin acetate implant + radiation versus radiation alone. The most frequently reported (greater than 5%) adverse experiences are listed below:

Additional adverse event data were collected for the combination therapy with radiation group over both the hormonal treatment and hormonal treatment plus radiation phases of the study. Adverse experiences occurring in more than 5% of patients in this group, over both parts of the study, were hot flashes (46%), diarrhea (40%), nausea (9%) and skin rash (8%).

Stage D2 Metastatic Carcinoma

 The following adverse experiences were reported during a multicenter clinical trial comparing Flutamide capsules + LHRH agonist versus placebo + LHRH agonist.

The most frequently reported (greater than 5%) adverse experiences during treatment with Flutamide capsules in combination with an LHRH agonist are listed in the table below. For comparison, adverse experiences seen with an LHRH agonist and placebo are also listed in the following table:

As shown in the table, for both treatment groups, the most frequently occurring adverse experiences (hot flashes, impotence, loss of libido) were those known to be associated with low serum androgen levels and known to occur with LHRH agonists alone.

The only notable difference was the higher incidence of diarrhea in the Flutamide + LHRH agonist group (12%), which was severe in 5% as opposed to the placebo + LHRH agonist (4%), which was severe in less than 1%.

In addition, the following adverse reactions were reported during treatment with Flutamide + LHRH agonist.

Cardiovascular System:hypertension in 1% of patients

Central Nervous System:CNS (drowsiness/confusion/depression/anxiety/nervousness) reactions occurred in 1% of patients

Gastrointestinal System: anorexia 4% and other GI disorders occurred in 6% of patients

Hematopoietic System:anemia occurred in 6%, leukopenia in 3% and thrombocytopenia in 1% of patients

Liver and Biliary System:hepatitis and jaundice in less than 1% of patients

Skin:irritation at the injection site and rash occurred in 3% of patients

Other:edema occurred in 4%, genitourinary and neuromuscular symptoms in 2% and pulmonary symptoms in less than 1% of patients

In addition, the following spontaneous adverse experiences have been reported during the marketing of Flutamide: hemolytic anemia, macrocytic anemia, methemoglobinemia, sulfhemoglobinemia, photosensitivity reactions (including erythema, ulceration, bullous eruptions and epidermal necrolysis) and urine discoloration. The urine was noted to change to an amber or yellow-green appearance which can be attributed to the Flutamide and/or its metabolites. Also reported were cholestatic jaundice, hepatic encephalopathy and hepatic necrosis. The hepatic conditions were often reversible after discontinuing therapy; however, there have been reports of death following severe hepatic injury associated with use of Flutamide.

Malignant breast neoplasms have occurred rarely in male patients being treated with Flutamide.

Abnormal Laboratory Test Values: Laboratory abnormalities including elevated SGOT, SGPT, bilirubin values, SGGT, BUN and serum creatinine have been reported.

Side Effects by Body System

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.

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.

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

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.

Nervous system

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

Renal

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

Cardiovascular

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

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.

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.

Endocrine

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

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.

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

Musculoskeletal

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

Psychiatric

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

Genitourinary

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

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.

Other side effects have included flutamide withdrawal syndrome.

Respiratory

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

Disclaimer: Every effort has been made to ensure that the information provided is accurate, up-to-date, and complete, but no guarantee is made to that effect. In addition, the drug information contained herein may be time sensitive and should not be utilized as a reference resource beyond the date hereof. This information does not endorse drugs, diagnose patients, or recommend therapy. This drug information is a reference resource designed as supplement to, and not a substitute for, the expertise, skill , knowledge, and judgement of healthcare practitioners in patient care. The absence of a warning for a given drug or drug combination in no way should be construed to indicate that the drug of drug combination is safe, effective, or appropriate for any given patient. Drugs.com does not assume any responsibility for any aspect of healthcare administered with the aid of information provided. The information contained herein is not intended to cover all possible uses, directions, precautions, warnings, drug interactions, allergic reactions, or adverse effects. If you have questions about the drugs you are taking, check with your doctor, nurse, or pharmacist.