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 anagrelide and abiraterone. Please also consult the relevant specialist information.
The reported changes in exposure correspond to the changes in the plasma concentration-time curve [ AUC ]. We did not detect any change in exposure to anagrelide. We currently cannot estimate the influence of abiraterone. We do not expect any change in exposure for abiraterone, when combined with anagrelide (100%).
The pharmacokinetic parameters of the average population are used as the starting point for calculating the individual changes in exposure due to the interactions.
Anagrelide has a mean oral bioavailability [ F ] of 70%, which is why the maximum plasma levels [Cmax] tend to change with an interaction. The terminal half-life [ t12 ] is rather short at 1.3 hours and constant plasma levels [ Css ] are reached quickly. Protein binding [ Pb ] is not known and the volume of distribution [ Vd ] is very large at 840 liters. The metabolism mainly takes place via CYP1A2.
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.
|Serotonergic Effects a||0||Ø||Ø|
Rating: According to our knowledge, neither anagrelide nor abiraterone increase serotonergic activity.
|Kiesel & Durán b||0||Ø||Ø|
Rating: According to our knowledge, neither anagrelide nor abiraterone increase anticholinergic activity.
QT time prolongation
Rating: In combination, anagrelide and abiraterone can potentially trigger ventricular arrhythmias of the torsades de pointes type.
General adverse effects
|Side effects||∑ frequency||ana||abi|
|Peripheral edema||36.8 %||21.0||20.0|
|Abdominal pain||16.0 %||16.0||n.a.|
Elevated ALT (13%): abiraterone
Elevated AST (13%): abiraterone
Dyspnea (12%): anagrelide
Cough (6%): anagrelide
Interstitial lung disease: anagrelide
Urinary tract infection (10%): abiraterone
Flatulence (10%): anagrelide
Vomiting (10%): anagrelide
Loss of appetite (8%): anagrelide
Dyspepsis (5%): anagrelide
Fever (9%): anagrelide
Malaise (6%): anagrelide
Chest pain (8%): anagrelide
Tachycardia (8%): anagrelide
Atrial fibrillation (2.6%): abiraterone
Angina pectoris (1.6%): abiraterone
Ventricular tachycardia: anagrelide
Rash (8%): anagrelide
Pruritus (6%): anagrelide
Backache (6%): anagrelide
Sepsis (5.5%): abiraterone
Hemorrhage (3%): anagrelide
Based on your answers and scientific information, we assess the individual risk of undesirable side effects. These recommendations are intended to advise professionals and are not a substitute for consultation with a doctor. In the restricted test version (alpha), the risk of all substances has not yet been conclusively assessed.
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.