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 abarelix and chloroquine. Please also consult the relevant specialist information.
The reported changes in exposure correspond to the changes in the plasma concentration-time curve [ AUC ]. We do not expect any change in exposure for abarelix, when combined with chloroquine (100%). We do not expect any change in exposure for chloroquine, when combined with abarelix (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.
The bioavailability of abarelix is unknown. The terminal half-life [ t12 ] is rather long at 316.8 hours and constant plasma levels [ Css ] are only reached after more than 1267.2 hours. The protein binding [ Pb ] is 97.5% strong. The metabolism via cytochromes is currently still being worked on.
The bioavailability of chloroquine is unknown. The terminal half-life [ t12 ] is rather long at 1098 hours and constant plasma levels [ Css ] are only reached after more than 4392 hours. Protein binding [ Pb ] is not known. About 45.0% of an administered dose is excreted unchanged via the kidneys and this proportion is seldom changed by interactions. The metabolism takes place via CYP2C8, CYP2D6 and CYP3A4, among others and the active transport takes place in particular via PGP.
|Serotonergic Effects a||0||Ø||Ø|
Rating: According to our knowledge, neither abarelix nor chloroquine increase serotonergic activity.
|Kiesel & Durán b||0||Ø||Ø|
Rating: According to our knowledge, neither abarelix nor chloroquine increase anticholinergic activity.
QT time prolongation
Rating: In combination, abarelix and chloroquine can potentially trigger ventricular arrhythmias of the torsades de pointes type.
General adverse effects
|Side effects||∑ frequency||aba||chl|
|Atrioventricular block||0.0 %||n.a.||0.0|
|Heart failure||0.0 %||n.a.||0.0|
|Ventricular fibrillation||0.0 %||n.a.||0.0|
|Ventricular tachycardia||0.0 %||n.a.||0.0|
|Aplastic anemia||0.0 %||n.a.||0.0|
|Hemolytic anemia||0.0 %||n.a.||0.0|
|Hypersensitivity reaction||0.0 %||n.a.||0.0|
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: The hemodialysis blood clearance of chloroquine was studied in four patients with chronic renal failure undergoing chronic hemodialysis. The patients were administered chloroquine (600 mg base) orally after a light breakfast. Blood samples were then obtained from arterial blood entering and venous blood leaving the dialysis machine at 0.0, 0.5, 1.0, 2.0, 4.0, and 6.0 h, and at 24.0 and 48.0 h post dialysis. The blood flow rate varied between 200 and 275 ml/min, while the dialysate flow rate was maintained at 500 ml/min. The samples were analyzed for chloroquine by high pressure liquid chromatography, and the dialysis clearance was calculated utilizing the formula: ClD = QB[(CA - CV)/CA]. The mean extraction ratios for chloroquine were 0.238, 0.317, 0.207, and 0.216 in the four patients during the 6-h dialysis period. The calculated dialysis clearances were 57.2, 77.0, 56.1, and 48.3 ml/min. Chloroquine hemodialysis clearance was 14.5% of total body clearance in normal subjects and in patients with chronic renal failure not on hemodialysis.
Abstract: The pharmacokinetics of chloroquine and its desethyl metabolite were studied in six patients with chronic renal failure and compared with a control group of twelve patients with normal renal function. Chloroquine was given as a single oral dose of 600 mg and blood levels monitored for 144 h. Plasma chloroquine concentrations were determined using an HPLC method. The plasma half-life of chloroquine was significantly higher in renal patients than in controls. This finding suggests that extra caution should be exercised when prescribing chloroquine for prolonged use in patients with renal insufficiency.
Abstract: Chloroquine has been used for many decades in the prophylaxis and treatment of malaria. It is metabolized in humans through the N-dealkylation pathway, to desethylchloroquine (DCQ) and bisdesethylchloroquine (BDCQ), by cytochrome P450 (CYP). However, until recently, no data are available on the metabolic pathway of chloroquine. Therefore, the metabolic pathway of chloroquine was evaluated using human liver microsomes and cDNA-expressed CYPs. Chloroquine is mainly metabolized to DCQ, and its Eadie-Hofstee plots were biphasic, indicating the involvement of multiple enzymes, with apparent Km and Vmax values of 0.21 mM and 1.02 nmol/min/mg protein 3.43 mM and 10.47 nmol/min/mg protein for high and low affinity components, respectively. Of the cDNA-expressing CYPs examined, CYP1A2, 2C8, 2C19, 2D6 and 3A4/5 exhibited significant DCQ formation. A study using chemical inhibitors showed only quercetin (a CYP2C8 inhibitor) and ketoconazole (a CYP3A4/5 inhibitor) inhibited the DCQ formation. In addition, the DCQ formation significantly correlated with the CYP3A4/5-catalyzed midazolam 1-hydroxylation (r = 0.868) and CYP2C8-catalyzed paclitaxel 6alpha-hydroxylation (r = 0.900). In conclusion, the results of the present study demonstrated that CYP2C8 and CYP3A4/5 are the major enzymes responsible for the chloroquine N-deethylation to DCQ in human liver microsomes.
Abstract: A patient with polymorphic ventricular tachycardia, long QT interval and conduction disorders secondary to long-term treatment with chloroquine is presented.
Abstract: Malaria is an endemic and potentially lethal disease transmitted by the protozoan parasite Plasmodium. It is currently endemic in more than 100 countries, which are visited by 125 million international travellers every year. For dialysis and renal insufficiency patients it becomes increasingly easier to travel to these countries thanks to the recent advances in renal replacement therapy. However, the pharmacokinetics of some prophylactic agents in malaria are altered, which may modify the effectiveness and safety of such treatments and the way they should be prescribed. Clinicians should be aware of these alterations which require subsequent dosage adjustments. This review provides recommendations on the use of antimalarial drugs, alone or in combination, in patients with renal impairment. These recommendations depend on the prevalence of Plasmodium falciparum chloroquine resistance, as defined by the WHO. Furthermore, fixed-dose combinations cannot be used in patients with creatinine clearance below 60 mL/min since the tablets available do not allow appropriate dosage adjustment for each drug. Chloroquine and proguanil require dosage adjustments, while atovaquone, doxycycline and mefloquine do not.
Abstract: Transporters in proximal renal tubules contribute to the disposition of numerous drugs. Furthermore, the molecular mechanisms of tubular secretion have been progressively elucidated during the past decades. Organic anions tend to be secreted by the transport proteins OAT1, OAT3 and OATP4C1 on the basolateral side of tubular cells, and multidrug resistance protein (MRP) 2, MRP4, OATP1A2 and breast cancer resistance protein (BCRP) on the apical side. Organic cations are secreted by organic cation transporter (OCT) 2 on the basolateral side, and multidrug and toxic compound extrusion (MATE) proteins MATE1, MATE2/2-K, P-glycoprotein, organic cation and carnitine transporter (OCTN) 1 and OCTN2 on the apical side. Significant drug-drug interactions (DDIs) may affect any of these transporters, altering the clearance and, consequently, the efficacy and/or toxicity of substrate drugs. Interactions at the level of basolateral transporters typically decrease the clearance of the victim drug, causing higher systemic exposure. Interactions at the apical level can also lower drug clearance, but may be associated with higher renal toxicity, due to intracellular accumulation. Whereas the importance of glomerular filtration in drug disposition is largely appreciated among clinicians, DDIs involving renal transporters are less well recognized. This review summarizes current knowledge on the roles, quantitative importance and clinical relevance of these transporters in drug therapy. It proposes an approach based on substrate-inhibitor associations for predicting potential tubular-based DDIs and preventing their adverse consequences. We provide a comprehensive list of known drug interactions with renally-expressed transporters. While many of these interactions have limited clinical consequences, some involving high-risk drugs (e.g. methotrexate) definitely deserve the attention of prescribers.