Warnings and Precautions Seizure In Study 1, conducted in patients with metastatic castration-resistant prostate cancer CRPC who ly received docetaxel, seizure occurred in 0. There is no clinical trial experience re-administering XTANDI to patients who experienced a seizure, and limited safety data are available in patients with predisposing factors for seizure. Study 1 excluded the use of concomitant medications that may lower threshold; Study 2 permitted the use of these medications.
Because of the risk of seizure associated with XTANDI use, patients should be advised of the risk of engaging in any activity during which sudden loss of consciousness could cause serious harm to themselves or others.
PRES is a neurological disorder which can present with rapidly evolving symptoms including seizure, headache, lethargy, confusion, blindness, and other visual and neurological disturbances, with or without associated hypertension. To learn more, please visit XtandiHCP. In Study 2, 1 patient in each treatment group 0.
Falls were not associated with loss of consciousness or seizure. Fall-related injuries were more severe in XTANDI patients, and included non-pathologic fractures, t injuries, and hematomas. No patients experienced hypertensive crisis.
Medical history of hypertension was balanced between arms. All rights reserved. All patients continued on GnRH therapy. Enzalutamide in metastatic prostate cancer before chemotherapy. N Engl J Med. Please see the package insert for full prescribing information.
If this drug is used during pregnancy, or if the patient becomes pregnant while taking this drug, apprise the patient of the potential hazard to the fetus and the potential risk for pregnancy loss. In Study 2, 1 of 0. Patients experiencing seizure were permanently discontinued from therapy and all seizure events resolved.
Limited safety data are available in patients with predisposing factors for seizure because these patients were generally excluded from the trials. These exclusion criteria included a history of seizure, underlying brain injury with loss of consciousness, transient ischemic attack within the past 12 months, cerebral vascular accident, brain metastases, and brain arteriovenous malformation.
Study 1 excluded the use of concomitant medications that may lower the seizure threshold, whereas Study 2 permitted the use of these medications. Because of the risk of seizure associated with XTANDI use, patients should be advised of the risk of engaging in any activity where sudden loss of consciousness could cause serious harm to themselves or others.
Two randomized clinical trials enrolled patients with metastatic prostate cancer that has progressed on androgen deprivation therapy GnRH therapy or bilateral orchiectomya disease setting that is also defined as metastatic CRPC. In both studies, patients received XTANDI mg orally once daily in the active treatment arm or placebo in the control arm.
All patients continued androgen deprivation therapy. Patients were allowed, but not required, to take glucocorticoids. The median duration of treatment was 8.
The most common adverse reaction leading to treatment discontinuation was seizure, which occurred in 0. Table 1. Adverse Reactions in Study 1 cont. Study 2: Chemotherapy-naive Metastatic Castration- Resistant Prostate Cancer Study 2 enrolled patients with metastatic CRPC who had not received prior cytotoxic chemotherapy, of whom received at least one dose of study drug.
The median duration of treatment was Table 2. Adverse Reactions in Study 2 cont. Fall-related injuries were more severe in patients treated with XTANDI and included non-pathologic fractures, t injuries, and hematomas. Because these reactions were 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. Co-administration of strong CYP3A4 inducers e. St John s wort may decrease enzalutamide exposure and should be avoided.
If co-administration with warfarin cannot be avoided, conduct additional INR monitoring. Risk Summary XTANDI can cause fetal harm when administered to a pregnant woman based on its mechanism of action and findings in animals. While there are no human data on the use of XTANDI in pregnancy and XTANDI is not indicated for use in women, it is important to know that maternal use of an androgen receptor inhibitor could affect development of the fetus.
Enzalutamide caused embryofetal toxicity in mice at exposures that were lower than in patients receiving the recommended dose. It is not known if enzalutamide is excreted in human milk. Because many drugs are excreted in human milk, and because of the potential for serious adverse reactions in nursing infants from XTANDI, a decision should be made to either discontinue nursing, or discontinue the drug taking into the importance of the drug to the mother.
No overall differences in safety or effectiveness were observed between these patients and younger patients. Other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. No initial dosage adjustment is necessary for patients with mild to moderate renal impairment. Patients with Hepatic Impairment Dedicated hepatic impairment trials compared the composite systemic exposure of enzalutamide plus N-desmethyl enzalutamide in volunteers with baseline mild, moderate, or severe hepatic impairment Child- Pugh Class A, B, or C, respectively versus healthy controls with normal hepatic function.
The composite AUC of enzalutamide plus N-desmethyl enzalutamide was similar in volunteers with mild, moderate, or severe baseline hepatic impairment compared to volunteers with normal hepatic function. No initial dosage adjustment is necessary for patients with baseline mild, moderate, or severe hepatic impairment.
In a dose escalation study, no seizures were reported at mg daily, whereas 3 seizures were reported, 1 each at mg, mg, and mg daily. Patients may be at increased risk of seizure following an overdose. 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.
Based on nonclinical findings in repeat-dose toxicology studies, which were consistent with the pharmacological activity of enzalutamide, male fertility may be impaired by treatment with XTANDI. Myrbetriq can increase blood pressure. Periodic blood pressure determinations are recommended, especially in hypertensive patients.
Urinary retention in patients with bladder outlet obstruction BOO and in patients taking antimuscarinic medications for the treatment of OAB has been reported in postmarketing experience in patients taking mirabegron. A controlled clinical safety study in patients with BOO did not demonstrate increased urinary retention in Myrbetriq patients; however, Myrbetriq should be administered with caution to patients with clinically ificant BOO. Myrbetriq should also be administered with caution to patients taking antimuscarinic medications for the treatment of OAB.
In some cases angioedema occurred after the first dose. Cases of angioedema have been reported to occur hours after.
Angioedema associated with upper airway swelling may be life threatening. Therefore, appropriate monitoring and dose adjustment may be necessary, especially with narrow therapeutic index drugs metabolized by CYP2D6, such as thioridazine, flecainide, and propafenone. Reference: 1. Myrbetriq [Prescribing Information]. See full prescribing information for Myrbetriq. Gastrointestinal disorders: dyspepsia, gastritis, abdominal distension In contrast, in OAB patients in clinical trials, the mean increase in systolic and diastolic blood pressure at the maximum recommended dose of 50 mg was approximately mmhg greater than placebo.
Worsening of pre-existing hypertension was reported infrequently in Myrbetriq patients. Infections and Infestations: sinusitis, rhinitis Investigations: GGT increased, AST increased, ALT increased, LDH increased Renal and urinary disorders: nephrolithiasis, bladder pain Urinary Retention in Patients with Bladder Outlet Obstruction and in Patients Taking Antimuscarinic Reproductive system and breast disorders: vulvovaginal pruritus, vaginal infection Medications for OAB Skin and subcutaneous tissue disorders: urticaria, leukocytoclastic vasculitis, rash, pruritus, purpura, lip edema Urinary retention in patients with bladder outlet obstruction BOO and in patients taking antimuscarinic Table 2 lists the rates of the most commonly reported adverse reactions, derived from all adverse events in medications for the treatment of OAB has been reported in postmarketing experience in patients taking patients treated with Myrbetriq 50 mg for up to 52 weeks in Study 4.
The most commonly reported adverse mirabegron.
Myrbetriq should also be administered with caution to patients taking antimuscarinic medications for the treatment of OAB [see Clinical Pharmacology Cases of angioedema have been reported to occur hours after the first dose or after multiple doses.
Therefore, appropriate Back Pain monitoring and dose adjustment may be necessary, especially with narrow therapeutic index drugs metabolized by CYP2D6, such as thioridazine, flecainide, and propafenone [see Drug Interactions 7. In three, 12 week, double-blind, placebo-controlled, safety and efficacy studies in patients with overactive Dry Mouth Dizziness Sinusitis Influenza Arthralgia Cystitis bladder Studies 1, 2, and 3Myrbetriq was evaluated for safety in patients, [see Clinical Studies 14 ]. Study 1 also included an active control.
For the combined Studies 1, 2, and 3, patients received Myrbetriq 25 mg, received Myrbetriq 50 mg, and received Myrbetriq mg once daily. In Study 4, in patients treated with Myrbetriq 50 mg once daily, adverse reactions leading to discontinuation reported by more than 2 patients and at a rate greater than active control included: constipation 0.
Serious adverse events reported by at least 2 patients and exceeding active control included cerebrovascular accident 0. Of these patients, received Myrbetriq in a 12 week study. In Study 4, patients received Myrbetriq continuously for at least 6 months, patients received Myrbetriq for at least 9 months, and patients received Myrbetriq for at least 1 year.
The most frequent adverse events 0. Atrial fibrillation 0.