QT time prolongation
Adverse drug events
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Explanations of the substances for patients
We have no additional warnings for the combination of abiraterone and febuxostat. Please also consult the relevant specialist information.
The changes in exposure mentioned relate to changes in the plasma concentration-time curve [AUC]. We do not expect any change in exposure for abiraterone, when combined with febuxostat (100%). We did not detect any change in exposure to febuxostat. We cannot currently estimate the influence of abiraterone.
The pharmacokinetic parameters of the average population are used as the starting point for calculating the individual changes in exposure due to the interactions.
Abiraterone has a mean oral bioavailability [ F ] of 50%, which is why the maximum plasma levels [Cmax] tend to change with an interaction. The terminal half-life [ t12 ] is 18 hours and constant plasma levels [ Css ] are reached after approximately 72 hours. The protein binding [ Pb ] is very strong at 99.8% and the volume of distribution [ Vd ] is very large at 2815 liters, The metabolism mainly takes place via CYP3A4.
The bioavailability of febuxostat is unknown. The terminal half-life [ t12 ] is 23.5 hours and constant plasma levels [ Css ] are reached after approximately 94 hours. Protein binding [Pb] is not known. The metabolism takes place via CYP1A2, CYP2C8 and CYP2C9, among others and the active transport takes place partly via UGT1A1, UGT1A9 and UGT2B7.
|Serotonergic Effects a||0||Ø||Ø|
Rating: According to our knowledge, neither abiraterone nor febuxostat increase serotonergic activity.
|Kiesel & Durán b||0||Ø||Ø|
Rating: According to our findings, neither abiraterone nor febuxostat increase anticholinergic activity.
QT time prolongation
Abiraterone can potentially increase QT time, but we do not know about torsades de pointes arrhythmias. We do not know of any QT-prolonging potential for febuxostat.
General adverse effects
|Side effects||∑ frequency||abi||feb|
|Peripheral edema||20.0 %||20.0||n.a.|
|Elevated ALT||15.6 %||13.0||3.0|
|Elevated AST||14.7 %||13.0||2.0|
|Urinary tract infection||10.0 %||10.0||n.a.|
|Atrial fibrillation||2.6 %||2.6||0.0|
|Angina pectoris||1.6 %||1.6||n.a.|
Nausea (1.2%): febuxostat
Stevens johnson syndrome: febuxostat
Toxic epidermal necrolysis: febuxostat
Cerebrovascular accident: febuxostat
Cardiac arrest: febuxostat
Diabetes mellitus: febuxostat
Based on your
Abstract: Three open-label, single-dose studies investigated the impact of hepatic or renal impairment on abiraterone acetate pharmacokinetics and safety/tolerability in non-cancer patients. Patients (n = 8 each group) with mild/moderate hepatic impairment or end-stage renal disease (ESRD), and age-, BMI-matched healthy controls received a single oral 1,000 mg abiraterone acetate (tablet dose); while patients (n = 8 each) with severe hepatic impairment and matched healthy controls received 125- and 2,000-mg abiraterone acetate (suspension doses), respectively (systemic exposure of abiraterone acetate suspension is approximately half to that of tablet formulation). Blood was sampled at specified timepoints up to 72 or 96 hours postdose to measure plasma abiraterone concentrations. Abiraterone exposure was comparable between healthy controls and patients with mild hepatic impairment or ESRD, but increased by 4-fold in patients with moderate hepatic impairment. Despite a 16-fold reduction in dose, abiraterone exposure in patients with severe hepatic impairment was about 22% and 44% of the Cmax and AUC∞ of healthy controls, respectively. These results suggest that abiraterone pharmacokinetics were not changed markedly in patients with ESRD or mild hepatic impairment. However, the capacity to eliminate abiraterone was substantially compromised in patients with moderate or severe hepatic impairment. A single-dose administration of abiraterone acetate was well-tolerated.
Abstract: Two novel oral drugs that target androgen signaling have recently become available for the treatment of metastatic castration-resistant prostate cancer (mCRPC). Abiraterone acetate inhibits the synthesis of the natural ligands of the androgen receptor, whereas enzalutamide directly inhibits the androgen receptor by several mechanisms. Abiraterone acetate and enzalutamide appear to be equally effective for patients with mCRPC pre- and postchemotherapy. Rational decision making for either one of these drugs is therefore potentially driven by individual patient characteristics. In this review, an overview of the pharmacokinetic characteristics is given for both drugs and potential and proven drug-drug interactions are presented. Additionally, the effect of patient-related factors on drug disposition are summarized and the limited data on the exposure-response relationships are described. The most important pharmacological feature of enzalutamide that needs to be recognized is its capacity to induce several key enzymes in drug metabolism. The potency to cause drug-drug interactions needs to be addressed in patients who are treated with multiple drugs simultaneously. Abiraterone has a much smaller drug-drug interaction potential; however, it is poorly absorbed, which is affected by food intake, and a large interpatient variability in drug exposure is observed. Dose reductions of abiraterone or, alternatively, the selection of enzalutamide, should be considered in patients with hepatic dysfunction. Understanding the pharmacological characteristics and challenges of both drugs could facilitate decision making for either one of the drugs.
Abstract: We present a case of a 77 year-old gentleman with previous coronary artery bypass grafting, admitted to hospital with recurrent torsades de pointes (TdP) due to abiraterone-induced hypokalaemia and prolonged QTc. The patient was on abiraterone and prednisone for metastatic prostate cancer. He required multiple defibrillations for recurrent TdP. Abiraterone is a relatively novel drug used in metastatic prostate cancer and we discuss this potential adverse effect and its management in this unusual presentation.