How should this medicine be used?
Praxis comes as a tablet to take by mouth. It is usually taken with or without food once a day, either in the morning or evening. Take Praxis at around the same time every day. You should begin taking Praxis on the same day you begin injecting the luteinizing hormone-releasing hormone. Follow the directions on your prescription label carefully, and ask your doctor or pharmacist to explain any part you do not understand. Take Praxis exactly as directed. Do not take more or less of it or take it more often than prescribed by your doctor.
Praxis along with the luteinizing hormone-releasing hormone may help stop the growth and spread of cancer cells but does not cure prostate cancer. Continue to take both Praxis and the luteinizing hormone-releasing hormone even if you feel better. Do not stop taking these medications without talking to your doctor.
What is Praxis (Casodex)?
Praxis is an anti-androgen. It works in the body by preventing the actions of androgens (male hormones).
Praxis is used together with another hormone to treat prostate cancer.
Praxis may also be used for purposes not listed in this medication guide.
In clinical studies, the most commonly reported side effects of Praxis (Casodex®) are shown here. Side effects sometimes have percentage ranges because they differed between clinical studies:
- Hot flashes (9 - 53%)
- Swelling of breast tissue with breast pain (48%)
- Breast pain (18%)
- Swelling of breast tissue (17%)
- Diarrhea (5 - 12%)
- Blood in the urine (4 - 12%)
- Flu-like symptoms (9%)
- Back pain (8%)
- Impotence (8%)
- Urinary tract infection (8%)
- Constipation (8%)
- High blood pressure (1 - 8%)
- Abdominal pain (7%)
- Weakness (7%)
- Joint pain (7%)
- Sore throat (7%)
- Infection (7%)
- Trouble controlling bladder (6%)
- Rash (6%)
- Weight gain (6%)
- Generalized pain (5%)
- Hernia (5%)
- Inflammation of lung airways (5%)
- Drowsiness (5%)
- Shortness of breath (2%)
Roughly 10 - 25% of patients discontinue Praxis due to unacceptable side effects.
Note: Blood in the urine was not related to treatment with Praxis in 98% of patients who experienced this.
The following adverse reactions have been identified during postapproval use of Praxis tablets. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.
Respiratory disorders : Interstitial lung disease (some fatal) including interstitial pneumonitis and pulmonary fibrosis, most often at doses greater than 50 mg
Hemorrhage: Increased PT/INR due to interaction between coumarin anticoagulants and Bicalutam >
Skin and subcutaneous tissue disorders : Photosensitivity
- Gynecomastia (swelling of the breast tissue) has mostly been reported in trials of Praxis using the 150 mg daily dose. The frequency of gynecomastia with 50 mg daily is rare
- Praxis may be given days or weeks before starting an injectable medication known as a LHRH agonist (example: leuprolide acetate, Lupron® or Eligard®). The timing is important to prevent tumor flare.
- A pharmacist should ALWAYS review your medication list to ensure that drug interactions are prevented or managed appropriately
- Clinical trials may exist for prostate cancer. Ask your doctor if any studies are currently enrolling in your area. If not, go to clinicaltrials.gov to search for other centers offering study medications
Drug-drug. Warfarin: increased Praxis effects
Drug-diagnostic tests. Alanine aminotransferase, alkaline phosphatase, aspartate aminotransferase, bilirubin, cholesterol, BUN, creatinine: increased levels
Hemoglobin, white blood cells: decreased values
Pharmacologic class: Nonsteroidal antiandrogen
Therapeutic class: Antineoplastic
Pregnancy risk category XGeneral side effects from Praxis (Casodex®)
- May caused liver injury. Call your doctor immediately if you notice yellowing of the skin or eyes
- Can cause swelling of breast tissue and breast pain when used at high doses (150 mg) - known as gynecomastia
- Patients commonly experience hot flashes while receiving therapy with Praxis
- May cause weakness, drowsiness, and flu-like symptoms
- Can cause back or joint pain
- Some patients may experience impotence (loss of sexual function)
- May cause abdominal pain, constipation, or diarrhea
- May cause high blood pressure
- Can cause trouble controlling bladder, bladder infection, or blood in the urine
- Sore throat
- Weight gain
- Inflammation of lung airways
- Shortness of breath
- Click on the Praxis (Casodex®) package insert below for reported side effects and possible drug interactions
Safety Data from Clinical Studies using Bicalutam > Praxis 150 mg is not approved for use either alone or with other treatments.
Two identical multi-center, randomized, open-label trials comparing Praxis 150 mg daily monotherapy to castration were conducted in patients that had locally advanced (T3-4, NX, M0) or metastatic (M1) prostate cancer.
Monotherapy — M1 Group
Praxis 150 mg daily is not approved for use in patients with M1 cancer of the prostate. Based on an interim analysis of the two trials for survival, the Data Safety Monitoring Board recommended that Praxis treatment be discontinued in the M1 patients because the risk of death was 25% (HR 1.25, 95% CI 0.87 to 1.81) and 31% (HR 1.31, 95% CI 0.97 to 1.77) higher in the Praxis treated group compared to that in the castrated group, respectively.
Locally Advanced (T3-4, NX, M0) Group
In addition to the above two studies, there are three other ongoing clinical studies that provide additional safety information for Praxis 150 mg, a dose that is not approved for use. These are three multi-center, randomized, double-blind, parallel group trials comparing Praxis 150 mg daily monotherapy (adjuvant to previous therapy or under watchful waiting) with placebo, for death or time to disease progression, in a population of 8113 patients with localized or locally advanced prostate cancer.
Praxis 150 mg daily is not approved for use as therapy for patients with localized prostate cancer who are candidates for watchful waiting. Data from a planned subgroup analysis of two of these trials in 1627 patients with localized prostate cancer who were under watchful waiting, revealed a trend toward decreased survival in the Praxis arm after a median follow-up of 7.4 years. There were 294 (37.7%) deaths in the Praxis treated patients versus 279 (32.9%) deaths in the placebo treated patients (localized watchful waiting group) for a hazard ratio of 1.16 (95% CI 0.99 to 1.37).
About bicalutam >
Praxis belongs to a group of medicines known as anti-androgens. This means that it blocks the actions of male sex hormones called androgens and it also reduces the amount of male hormones (such as testosterone) that your body produces.
Dosage Forms And Strength
CASODEX ® (Praxis) 50 mg tablets for oral administration.
White, film-coated tablets (identified on one side with "CDX50" and on the reverse with the "CASODEX logo") are supplied in unit dose bottles of 30 tablets (0310-0705-30).
Carcinogenesis, Mutagenesis, Impairment of Fertility
Two-year oral carcinogenicity studies were conducted in both male and female rats and mice at doses of 5, 15, or 75 mg/kg/day of Praxis. A variety of tumor target organ effects were identified and were attributed to the antiandrogenicity of Praxis, namely, testicular benign interstitial (Leydig) cell tumors in male rats at all dose levels (the steady-state plasma concentration with the 5 mg/kg/day dose is approximately 0.7 times the human exposure at the recommended dose) and uterine adenocarcinoma in female rats at 75 mg/kg/day (approximately 1.5 times the human exposure at the recommended dose). There is no evidence of Leydig cell hyperplasia in patients; uterine tumors are not relevant to the indicated patient population.
A small increase in the incidence of hepatocellular carcinoma in male mice given 75 mg/kg/day of Praxis (approximately 4 times the human exposure at the recommended dose) and an increased incidence of benign thyroid follicular cell adenomas in rats given 5 mg/kg/day (approximately 0.7 times the human exposure at the recommended dose) and above were recorded. These neoplastic changes were progressions of non-neoplastic changes related to hepatic enzyme induction observed in animal toxicity studies. Enzyme induction has not been observed following Praxis administration in man. There were no tumorigenic effects suggestive of genotoxic carcinogenesis.
A comprehensive battery of both in vitro and in vivo genotoxicity tests (yeast gene conversion, Ames, E. coli , CHO/HGPRT, human lymphocyte cytogenetic, mouse micronucleus, and rat bone marrow cytogenetic tests) has demonstrated that Praxis does not have genotoxic activity.
In repeat-dose toxicology studies, atrophy of seminiferous tubules of the testes has been observed for all species examined, which is a predicted class effect with antiandrogens. In the 6-and 12-month rat study, testicular atrophy was seen at approximately 2 times the human exposure at the recommended dose. In the 12-month dog study, the incidence of testicular atrophy was seen at approximately 7 times the human exposure at the recommended dose. In male rats administered 250 mg/kg/day (approximately 2 times human exposure at the recommended dose), the precoital interval and time to successful mating were increased in the first pairing, but no effects on fertility following successful mating were seen. These effects were reversed by 7 weeks after the end of an 11-week period of dosing.
Female rats dosed at 1, 10 and 250 mg/kg/day (less than to 2 times the human exposure at the recommended dose) had increased estrous cycle irregularity but there was no effect on fertility.
In a peri-and post-natal development study, female offspring of rats receiving doses of 10 mg/kg/day (approximately 0.7 times the human exposure at the recommended clinical dose) and above had reduced pregnancy rates. Administration of Praxis to pregnant females resulted in feminization of the male offspring leading to hypospadias at doses of 10 mg/kg/day (approximately 0.7 times the human exposure at the recommended dose) and above. Affected male offspring were also impotent.
Mechanism of Injury
The mechanism of Praxis hepatotoxicity is unknown. It is metabolized by the liver via the cytochrome P450 system, largely via CYP 3A4 which it can inhibit and thus cause drug-drug interactions. Thus, liver injury from Praxis may be caused by toxic metabolites of the agent. The lower frequency of hepatotoxicity from Praxis compared to flutamide may be due to its lower dose or its lower rate of hepatic metabolism.