Posaconazole–digoxin drug–drug interaction mediated by inhibition of P-glycoprotein

2018 ◽  
Vol 25 (7) ◽  
pp. 1758-1761 ◽  
Author(s):  
Abby C Shumaker ◽  
Heather M Bullard ◽  
Jane Churpek ◽  
Randall W Knoebel
Keyword(s):  
Atrial Fibrillation ◽  
Drug Interactions ◽  
Antifungal Agents ◽  
Polymorphic Ventricular Tachycardia ◽  
Glycoprotein P ◽  
P Glycoprotein ◽  
Ventricular Response ◽  
Clinically Significant ◽  
P450 Isozymes ◽  
Cytochrome P450 Isozymes

Drug–drug interactions between digoxin and the triazole antifungal agents, mediated via various cytochrome P450 isozymes, have been described in the literature. Posaconazole is not extensively metabolized by these isozymes but is both a p-glycoprotein (P-gp) substrate and inhibitor. To our knowledge, there have been no published cases of clinically significant posaconazole-digoxin drug–drug interactions. We report an interaction between posaconazole (300 mg by mouth daily) and digoxin (0.25 mg by mouth daily, Monday through Friday) resulting in atrial fibrillation with slow ventricular response and degenerating into polymorphic ventricular tachycardia.

scholarly journals Drug – Drug Interactions Between Newer Anti- Retroviral Drugs And Anti Epileptics - A Review

2020 ◽  
Vol 11 (3) ◽  
pp. 2963-2967
Author(s):  
Vaishnavi S ◽  
Balaji S ◽  
Ramesh M ◽  
Mothi S N ◽  
Swamy V H T ◽  
...  
Keyword(s):  
Human Immunodeficiency Virus ◽  
Drug Resistance ◽  
Drug Interactions ◽  
Drug Toxicity ◽  
Glycoprotein P ◽  
P Glycoprotein ◽  
Immunodeficiency Virus ◽  
Pharmacokinetic Properties ◽  
Mechanism Of Interaction ◽  
Cyp 3A

Drug – Drug Interactions (DDIs) are the leading cause of drug toxicity and emergence of drug resistance, ultimately leading to increased burden in People Living with Human Immunodeficiency Virus (PLHIV). On an average 55 % of people on Anti Retroviral Therapy (ARVs) are co-administered with Anti Epileptic Drugs (AEDs). The introduction of newer anti-retroviral drugs such as dolutegravir, bictegravir, emtricitabine, doravirine are proven to have less side effects, high tolerability and effective decrease in the viral load, but the risk of DDIs still stands to be high. This review briefly describes about the pharmacokinetic properties of dolutegravir, bictegravir, emtricitabine, doravirine, mechanism of interaction between the above mentioned ARVs and AEDs, effect of DDIs on ARVs, effect of DDIs on interacting AEDs, outcome of DDIs and possible management of DDIs. The pharmacokinetic type of DDIs was observed between the ARVs and AEDs. The majority of DDIs were found affecting the metabolism and the absorption of the drugs. UGT1A1, CYP 3A are the two important classes of metabolic enzymes involved in the DDIs and p- glycoprotein (P-gp) is the transporter involved in the DDIs affecting the absorption. Significant interactions have been found in between the above mentioned newer ARV’s with carbamazepine, oxcarbazepine, phenytoin and phenobarbitol.

scholarly journals Potential clinically significant drug interactions of drugs with fruit and berry juices

2021 ◽  
Vol 31 (4) ◽  
pp. 44-51
Author(s):  
A.P. Pereverzev ◽  
O.D. Ostroumova
Keyword(s):  
Drug Interactions ◽  
Apple Juice ◽  
Grapefruit Juice ◽  
Grape Juice ◽  
Cyp1a2 Activity ◽  
P Glycoprotein ◽  
Presystemic Metabolism ◽  
Complex Chemical Composition ◽  
Rate Of Absorption ◽  
Clinically Significant

Any drug can potentially cause adverse drug reactions (ADRs), including serious and fatal. Some of them are caused by interactions with food, in particular, fruit and berry juices. Juices have a complex chemical composition and each of the chemicals can interact with drugs. Grapefruit juice is one of the most popular and well-studed in terms of potential drug interactions juices. Grapefruit juice is an inhibitor of CYP3A enzymes in the intestine involved in the presystemic metabolism of drug substrates. Therefore, it can increase their absorption. Apple juice at a concentration of 5% significantly reduces the activity of OATP, but not the activity of P-glycoprotein, which, for example, leads to a decrease in AUC and Cmax of fexofenadine to 30- 40% relative to the concentration of fexofenadine in patients drinking only water. Taking 200 ml of grape juice can reduce the concentration of phenacetin in blood plasma and increase the ratio of AUC of paracetamol to phenacetin due to the induction of CYP1A2 activity by grape juice flavonoids or by reducing the rate of absorption of phenacetin. To prevent ADRs, it is recommended to take drugs with water and and not consume simultaneously juices that are known to interact with drugs.

scholarly journals Drug–Drug Interactions of 257 Antineoplastic and Supportive Care Agents With 7 Anticoagulants: A Comprehensive Review of Interactions and Mechanisms

2020 ◽  
Vol 26 ◽  
pp. 107602962093632 ◽  
Author(s):  
Érique José F. Peixoto de Miranda ◽  
Thamy Takahashi ◽  
Felipe Iwamoto ◽  
Suzete Yamashiro ◽  
Eliana Samano ◽  
...  
Keyword(s):  
Tyrosine Kinase ◽  
Supportive Care ◽  
Drug Interactions ◽  
Tyrosine Kinase Inhibitors ◽  
Kinase Inhibitors ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
P Glycoprotein ◽  
Clinically Significant ◽  
Potentially Clinically Significant

Data on drug–drug interactions (DDI) of antineoplastic drugs with anticoagulants is scarce. We aim to evaluate factors associated with DDI of antineoplastic and supportive care drugs with anticoagulants resulting in modification of pharmacokinetics of these last mentioned. A literature review on DDI databases and summaries of products characteristics (SmPC) was done. Drug–drug interactions of 257 antineoplastic and supportive care drugs with direct oral anticoagulants (DOACs), warfarin, enoxaparin, or fondaparinux were categorized as no clinically significant expected DDI, potentially weak DDI, potentially clinically significant DDI, and recommendation against coadministration. Logistic regression models were performed to analyze the association between the dependent variable potentially clinically significant interaction/recommendation against coadministration and the mechanisms of DDI. Of the 1799 associations, 84.4% were absence of DDI, 3.6% potentially weak DDI, 10.2% potentially clinically relevant DDI, and 2.0% recommendation against coadministration. Warfarin has higher DDI potential than other anticoagulants. Enoxaparin and fondaparinux have fewer DDI than others. There was no difference between DOACs. Drug–drug interactions with apixaban and rivaroxaban was independently associated with the absence of CYP3A4 competition, P-glycoprotein inhibition, CYP3A4 induction, and drug class of tyrosine kinase inhibitors. Drug–drug interactions with dabigatran and edoxaban was associated with inhibition of P-glycoprotein and tyrosine kinase inhibitors. Warfarin, induction of CYP3A4, and inhibition of CYP2C9. Enoxaparin and fondaparinux, only tyrosine kinase inhibitors. Direct oral anticoagulants did not differ regarding DDI with antineoplastic agents. Warfarin presented more DDI than other anticoagulants. P-glycoprotein inhibition and CYP3A4 induction were independently associated with DDI of antineoplastic agents with DOACs.

Interactions between cardiology and oncology drugs in precision cardio-oncology

2021 ◽  
Vol 135 (11) ◽  
pp. 1333-1351
Author(s):  
Sailaja Kamaraju ◽  
Meera Mohan ◽  
Svetlana Zaharova ◽  
Brianna Wallace ◽  
Joseph McGraw ◽  
...  
Keyword(s):  
Drug Interactions ◽  
Treatment Approach ◽  
Interdisciplinary Collaboration ◽  
Multidisciplinary Treatment ◽  
Close Attention ◽  
Glycoprotein P ◽  
Patients With Cancer ◽  
P Glycoprotein ◽  
Cardiovascular Side Effects

Abstract Recent advances in treatment have transformed the management of cancer. Despite these advances, cardiovascular disease remains a leading cause of death in cancer survivors. Cardio-oncology has recently evolved as a subspecialty to prevent, diagnose, and manage cardiovascular side effects of antineoplastic therapy. An emphasis on optimal management of comorbidities and close attention to drug interactions are important in cardio-oncologic care. With interdisciplinary collaboration among oncologists, cardiologists, and pharmacists, there is potential to prevent and reduce drug-related toxicities of treatments. The cytochrome P450 (CYP450) family of enzymes and the P-glycoprotein (P-g) transporter play a crucial role in drug metabolism and drug resistance. Here we discuss the role of CYP450 and P-g in drug interactions in the field of cardio-oncology, provide an overview of the cardiotoxicity of a spectrum of cancer agents, highlight the role of precision medicine, and encourage a multidisciplinary treatment approach for patients with cancer.

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