At steady-state, Xtandi reduced the plasma exposure to midazolam (CYP3A4 substrate), warfarin (CYP2C9 substrate), and omeprazole (CYP2C19 substrate). Consistent MFS results were also observed in pre-specified and stratified patient sub-groups of PSADT (< 6 months or 6 months) and use of a prior bone-targeting agent (yes or no). Permanently discontinue XTANDI in patients who develop a seizure during treatment. Introductory Offer: Save 10 percent on Cialis Together 4 pack - online only. Results showed that in vivo, at steady-state, Xtandi did not cause clinically meaningful changes in exposure to the CYP1A2 or CYP2D6 substrates. cancer: Overall survival and radiographic progression-free survival (rPFS) were assessed. Xtandi was used as a subsequent therapy in 2% of Xtandi-treated patients and 29% of placebo-treated patients. ARCHES randomized 1150 patients with mCSPC, of whom 1146 received at least one dose of study drug. This site is intended for US Healthcare Professionals only. A dedicated renal impairment trial for Xtandi has not been conducted. XTANDI, Astellas, and the flying star logo are registered trademarks of AstellasPharmaInc. XTANDI Support Solutions, a component of Astellas Pharma Support Solutions, is a registered trademark of AstellasPharmaUS,Inc. QUICK START+ is a registered trademark of AstellasPharmaUS,Inc. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate the frequency or establish a causal relationship to drug exposure. In a drug-drug interaction trial in healthy volunteers, a single 160 mg oral dose of Xtandi was administered alone or after multiple oral doses of gemfibrozil (strong CYP2C8 inhibitor). Erleada vs. Xtandi: What's the difference? Helps you get and maintain an erection when you need it. The median age was 69 years (range 41-92) and the racial distribution was 92.7% Caucasian, 3.9% Black, 1.1% Asian, and 2.1% Other. The most common adverse reactions leading to treatment discontinuation were back pain and pathological fracture, which occurred in 3.8% of Xtandi-treated patients for each event and in 2.1% and 1.6% of bicalutamide-treated patients, respectively. Contraindications-XTANDI can cause fetal harm when administered to a pregnant woman based on its mechanism of action. The median duration of treatment was 8.3 months with Xtandi and 3.0 months with placebo. In TERRAIN, the bicalutamide-controlled study of chemotherapy-naive mCRPC patients, Grade 3-4 ARs were reported in 39% of XTANDI patients and 38% of bicalutamide patients. Three of the 8 patients experienced a second seizure during continued treatment with Xtandi after their first seizure resolved. Based on pharmacokinetic data from studies in Japanese and Chinese patients with prostate cancer, there were no clinically relevant differences in exposure among the populations. In vitro, enzalutamide and N-desmethyl enzalutamide are inhibitors of human P-glycoprotein, while the major inactive carboxylic acid metabolite is not. Table 4 shows adverse reactions reported in PROSPER that occurred at a 2% higher frequency in the Xtandi arm than in the placebo arm. Do not chew, dissolve or open the capsules. Permanently discontinue Xtandi for serious hypersensitivity reactions. Permanent discontinuation due to AEs as the primary reason was reported in 5% of XTANDI patients and 4% of placebo patients. Falls and Fracturesoccurred in patients receiving XTANDI. Patients were randomized 2:1 and received either Xtandi at a dose of 160 mg once daily (N = 930) or placebo (N = 465). Stimulation of tumour cell growth via the androgen . Discontinuations with an AE as the primary reason were reported for 8% of XTANDI patients and 6% of bicalutamide patients. Kaplan-Meier Curves of Overall Survival in AFFIRM. 280168-XTA-USA. Basch E, Does it lower prostate-specific antigen (PSA)? Seizure occurred in 0.5% of patients receiving Xtandi in seven randomized clinical trials. Grade 3-4 ischemic events occurred in 1.4% of patients on the Xtandi arm compared to 0.7% on the placebo arm. Based on findings in animal reproduction studies, advise male patients with female partners of reproductive potential to use effective contraception during treatment and for 3 months after the last dose of Xtandi [see Use in Specific Populations (8.1)]. XTANDI [package insert]. Ninety-one percent of patients had metastases in bone and 23% had visceral involvement in the lung and/or liver. Avoid coadministration with strong CYP3A4 inducers. Warning and Precautions- In the randomized phase 3 clinical trial, seizure occurred in 0.9% of patients on XTANDI. Different chemotherapy drugs target cells . Enzalutamide is primarily eliminated by hepatic metabolism. Xtandi is an androgen receptor inhibitor that is usually used in conjunction with androgen deprivation therapy for the treatment of prostate cancer. You may report side effects to FDA at 1-800-FDA-1088. PROSPER enrolled 1401 patients with non-metastatic CRPC who were randomized 2:1 to receive either Xtandi orally at a dose of 160 mg once daily (N = 933) or placebo orally once daily (N = 468). Mechanism of action. In a single-arm trial designed to assess the risk of seizure in patients with pre-disposing factors for seizure, 8 of 366 (2.2%) Xtandi-treated patients experienced a seizure. In these seven trials, the median duration of treatment was 13.8 months (range: <0.1 to 87.6) in the Xtandi group. As you have read, Xtandi is a very powerful medication. St Johns wort may decrease enzalutamide exposure and should be avoided. Swallow capsules or tablets whole. Mechanism of Action. Radiographic progression-free survival (rPFS) was defined as the time from randomization to the first objective evidence of radiographic progression as assessed by ICR or death, whichever occurred first. Discontinuations due to adverse events (AEs) were reported for 16% of XTANDI-treated patients. Inactive ingredients: caprylocaproyl polyoxylglycerides, butylated hydroxyanisole, butylated hydroxytoluene, gelatin, sorbitol sorbitan solution, glycerin, purified water, titanium dioxide, black iron oxide. Study treatment continued until disease progression (evidence of radiographic progression, a skeletal-related event, or clinical progression) and the initiation of a cytotoxic chemotherapy or an investigational agent, unacceptable toxicity, or withdrawal. Enzalutamide is a strong CYP3A4 inducer and a moderate CYP2C9 and CYP2C19 inducer in humans. If co-administration of a strong CYP3A4 inducer with Xtandi cannot be avoided, increase the dose of Xtandi [see Dosage and Administration (2.2) and Clinical Pharmacology (12.3)]. No initial dosage adjustment is necessary for patients with mild to moderate renal impairment. The safety and efficacy of Xtandi have not been established in females. Enzalutamide has been shown to competitively inhibit androgen binding to androgen receptors; and consequently, inhibits nuclear translocation of androgen receptors and their interaction with DNA. The following patient demographics and baseline characteristics were balanced between the two treatment arms. The potential effect of severe renal impairment or end-stage renal disease on enzalutamide pharmacokinetics cannot be determined as clinical and pharmacokinetic data are available from only one patient [see Use in Specific Populations (8.6)]. https://www.auanet.org/guidelines/advanced-prostate-cancer. Mechanism of Action. Patients received Xtandi 160 mg (N= 4081) or placebo orally once daily (N= 2472) or bicalutamide 50 mg orally once daily (N= 387). Advise patients who experience any symptoms of hypersensitivity to temporarily discontinue XTANDI and promptly seek medical care. Xtandi may cause serious side effects including: Your healthcare provider will stop treatment with Xtandi if you have serious side effects. The tablet film-coat contains hypromellose, talc, polyethylene glycol, titanium dioxide, and ferric oxide. Monitor for signs and symptoms of ischemic heart disease. PSA is a protein made by prostate cells. The major efficacy outcome of the study was metastasis-free survival (MFS), defined as the time from randomization to whichever of the following occurred first 1) loco-regional and/or distant radiographic progression per BICR or 2) death up to 112 days after treatment discontinuation without evidence of radiographic progression. Time to new antineoplastic therapy was an additional efficacy endpoint. PRES is a neurological disorder that can present with rapidly evolving symptoms including seizure, headache, lethargy, confusion, blindness, and other visual and neurological disturbances, with or without associated hypertension. Overall, 10 patients (1.7%) receiving Xtandi died from adverse events. Mechanism of Action Enzalutamide is an androgen receptor inhibitor that acts on different steps in the androgen receptor signaling pathway. AFFIRM (NCT00974311): Xtandi versus Placebo in Metastatic CRPC Following Chemotherapy. Falls and Fracturesoccurred in patients receiving XTANDI. This site is intended for US Healthcare Professionals only. It may cause fetal harm. The concomitant use of strong CYP2C8 inhibitors should be avoided if possible. Systemic therapy in men with metastatic Despite low or even undetectable levels of serum androgen, androgen receptor signalling continues to promote disease progression. Inactive ingredients: hypromellose acetate succinate, microcrystalline cellulose, colloidal silicon dioxide, croscarmellose sodium, and magnesium stearate. Safety and effectiveness of Xtandi in pediatric patients have not been established. XTANDI (enzalutamide) is indicated for the treatment of patients with: Enzalutamide (XTANDI) is the first and only novel hormone therapy recommended by the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) as a Category 1 treatment option* for certain patients with mCSPC, nmCRPC, and mCRPC1, NCCN Guidelines recommend enzalutamide (XTANDI) with androgen deprivation therapy as a Category 1 treatment option* for patients with mCSPC, NCCN Guidelines recommend enzalutamide (XTANDI) with continued androgen deprivation therapy as a Category 1 treatment option* for patients with nmCRPC when PSADT is 10 months, NCCN Guidelines recommend enzalutamide (XTANDI) with continued androgen deprivation therapy as a Category 1 first-line treatment option* for patients with mCRPC, *A Category 1 recommendation is based on high-level evidence and indicates uniform NCCN consensus that the intervention isappropriate.1, For patients with mCRPC and no prior docetaxel, and no prior novel hormone therapy.1, Enzalutamide (XTANDI) is the first novel hormone therapy recommended with a Strong Recommendation* by the American Urological Association (AUA) in mCSPC, nmCRPC, and mCRPC2, Strong Recommendation Based on Evidence Level Grade A, For patients with mCSPC in combination with continued androgen deprivation therapy, For patients with nmCRPC on continued androgen deprivation therapy at high risk for developing metastatic disease (PSADT 10 months), For newly diagnosed mCRPC patients on continued androgen deprivation therapy. The reasons for death in 2 patients included heart disease (n=2) and sudden death (n=2). Ischemic events led to death in 0.4% of patients on XTANDI compared to 0.1% on placebo. Patients randomized to either arm discontinued treatment for radiographic disease progression confirmed by BICR, initiation of new treatment, unacceptable toxicity, or withdrawal. Why has it stopped working and what do I take next? Table 5 shows adverse reactions reported in ARCHES that occurred at a 2% higher frequency in the Xtandi arm than in the placebo arm. Enzalutamide did not induce mutations in the bacterial reverse mutation (Ames) assay and was not genotoxic in either the in vitro mouse lymphoma thymidine kinase (Tk) gene mutation assay or the in vivo mouse micronucleus assay. Androgens (male sex hormones) are a class of hormones that control the development and maintenance of male characteristics. XTANDI can cause fetal harm and loss of pregnancy when administered to a pregnant female. In the combined data from four randomized placebo-controlled clinical trials, hypertension was reported in 12% of patients receiving Xtandi and 5% of patients receiving placebo. NCCN Guidelines recommend enzalutamide (XTANDI) with continued androgen deprivation therapy as a Category 1 first-line treatment option* for patients with mCRPC . Hypertension led to study discontinuation in < 1% of patients in each arm. Excursions permitted from 15C to 30C (59F to 86F). Xtandi is a registered trademark of Astellas Pharma Inc. Xtandi is a prescription medicine used to treat men with prostate cancer that: It is not known if Xtandi is safe and effective in females. A diagnosis of PRES requires confirmation by brain imaging, preferably magnetic resonance imaging (MRI). In AFFIRM, a total of 1199 patients who had received prior docetaxel-based chemotherapy were randomized 2:1 to receive either Xtandi orally at a dose of 160 mg once daily (N = 800) or placebo orally once daily (N = 399). No large difference (i.e., greater than 20 ms) was observed between the mean QT interval change from baseline in patients treated with Xtandi and that in patients treated with placebo, based on the Fridericia correction method. Discontinuations due to adverse events were reported for 6% of Xtandi-treated patients. The median time to onset of fracture was 336 days (range: 2 to 1914 days) for patients treated with Xtandi. Seizure occurred in 0.5% of patients receiving XTANDI in seven randomized clinical trials. If co-administration of Xtandi with a strong CYP2C8 inhibitor cannot be avoided, reduce the dose of Xtandi [see Dosage and Administration (2.2) and Clinical Pharmacology (12.3)]. In a study of patients with predisposing factors for seizure, 2.2% of XTANDI-treated patients experienced a seizure. Save 2.20. Hypersensitivityreactions, including edema of the face (0.5%), tongue (0.1%), or lip (0.1%) have been observed with XTANDI in seven randomized clinical trials. Medical history of hypertension was balanced between arms. If you take too much Xtandi, call your healthcare provider or go to the nearest emergency room right away. Medically reviewed by Drugs.com. In PREVAIL, 1717 chemotherapy-nave patients were randomized 1:1 to receive either Xtandi orally at a dose of 160 mg once daily (N = 872) or placebo orally once daily (N = 845). Permanently discontinue Xtandi in patients who develop a seizure during treatment. [10] It is typically used together with a gonadotropin-releasing hormone (GnRH) analogue or surgical removal of the testicles to treat metastatic prostate cancer (mPC). All rights reserved. The inactive ingredients are hypromellose acetate succinate, microcrystalline cellulose, colloidal silicon dioxide, croscarmellose sodium, and magnesium stearate. Figure 4. Ninety-eight percent of patients had objective evidence of disease progression at study entry. Patients in the study had one or more of the following predisposing factors: use of medications that may lower the seizure threshold, history of traumatic brain or head injury, history of cerebrovascular accident or transient ischemic attack, and Alzheimers disease, meningioma, or leptomeningeal disease from prostate cancer, unexplained loss of consciousness within the last 12months, history of seizure, presence of a space occupying lesion of the brain, history of arteriovenous malformation, or history of brain infection. Monitor and manage patients at risk for fractures according to established treatment guidelines and consider use of bone-targeted agents. The median age at randomization was 74 years (range 50-95) and 23% were 80 years of age or older. Advise patients of the risk of developing a seizure while taking XTANDI and of engaging in any activity where sudden loss of consciousness could cause serious harm to themselves or others. Enzalutamide is 97% to 98% bound to plasma proteins, primarily albumin. The plasma enzalutamide pharmacokinetics are adequately described by a linear two-compartment model with first-order absorption. Purpose Enzalutamide, a potent oral androgen receptor inhibitor, improves survival in men with metastatic castration-resistant prostate cancer (CRPC) before and after chemotherapy. Enzalutamide is an androgen receptor inhibitor that acts on different steps in the androgen receptor signaling pathway. Population pharmacokinetic analyses showed that weight (range: 46 to 163 kg) and age (range: 41 to 92 yr) do not have a clinically meaningful influence on the exposure to enzalutamide. The mean apparent volume of distribution (V/F) of enzalutamide in patients after a single oral dose is 110 L (29% CV). In a study of patients had metastases in bone and 23 % were 80 years of age or older duration... 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