scholarly journals Potential clinically significant life-threatening drug–drug interactions of lopinavir and ritonavir used in the treatment of COVID-19

2020 ◽  
Vol 1 ◽  
Author(s):  
Mohitosh Biswas

AbstractPotential clinically significant life-threatening drug–drug interactions (DDIs) of lopinavir (LPV) and ritonavir (RTV) used in the treatment of COVID-19 is not systematically reviewed. It was aimed to identify severe DDI pairs of LPV/RTV from international resources predicted to cause life-threatening adverse drug reactions (ADRs). Severe DDI pairs predicted to cause life-threatening ADRs were identified from the FDA and Liverpool COVID-19 prescribing information of LPV/RTV. In total, 62 severe DDI pairs were identified from the FDA and Liverpool COVID-19 resources predicted to cause life-threatening ADRs in patients with COVID-19. Of these, seven unique DDI pairs (11.3%; 95% CI 3%–19%) were identified from the FDA only whereas 45 unique DDI pairs (72.6%; 95% CI 61%–84%) were identified from the Liverpool COVID-19 drug interactions resource. Of interest, only 10 DDI pairs (16.1%; 95% CI 7%–25%) were recognized by both of these drug interaction resources. Clinicians should not entirely rely on any individual DDI resource for checking life threatening ADRs of LPV/RTV in patients with COVID-19.

2016 ◽  
Vol 36 (suppl_1) ◽  
Author(s):  
Margaret McShane ◽  
Louis Radulovic ◽  
Charles L Bisgaier

Background: Gemcabene is a novel lipid-regulating compound being developed as an adjunct to diet and statin therapy for dyslipidemia treatment. Patients with dyslipidemia typically take many medications often including statins and it is essential to understand potential risk of drug-drug interactions (DDI) to minimize the risk of adverse drug reactions. In the best circumstances, drugs entering the market will provide metabolic or transport pathways that do not interfere with commonly co-administered drugs. The current studies provide the analysis of potential drug interactions with gemcabene both in vitro and in vivo . Methods: Caco-2 cells were used to assess the potential P-gp substrate and inhibitor interaction and the major drug-metabolizing CYP450 isozymes and FMO-3 were used to assess the potential CYP450 and FM0-3 metabolism interaction. The results from the in vitro P-gp and CYP450 studies was correlated with the results of three DDI clinical studies with digoxin, atorvastatin and simvastatin. Results: In an open-label, multiple-dose study in 12 healthy subjects, gemcabene (900 mg) did not significantly affect the exposure (Cmax and AUC 0-24 ) of digoxin (0.25 mg). Specifically, the 90% confidence interval for digoxin AUC (0-24) ratios were within the 80% to 125% range, thus confirming the in vitro results of no DDI with a P-gp substrate. In two open-label, multiple-dose studies in healthy volunteers, gemcabene (900 mg) did not significantly affect the exposure (Cmax and AUC 0-24 ) of atorvastatin (80 mg) or simvastatin (80 mg) thus confirming the in vitro results of no DDI with CYP450 (see Figure below). Conclusion: These results suggest gemcabene is unlikely to elicit a metabolic (i.e., CYP450 or FMO3) or P-gp-mediated drug interaction. Gemcabene (900 mg) was well-tolerated in combination with highest dose of atorvastatin and simvastatin. Clinical Implications: Understanding potential for drug interactions minimizes the risk of adverse drug reactions.


1979 ◽  
Vol 13 (12) ◽  
pp. 774-777 ◽  
Author(s):  
Jerry C. Hood ◽  
Jon R. Miller

Pharmacies currently using computers to detect drug-drug interactions may not be fully utilizing the computers' programs. Potential drug-disease interactions and some potential adverse drug reactions not traditionally defined as interactions can be detected by extending the basic concept of cross-referencing. For example, certain clinically important ADRs are readily detected by cross-referencing drugs which are often used to treat the results of specific ADRs with certain causative agents. The potential therapeutic implications of such a system when restricted to clinically significant ADRs can be readily appreciated, especially in situations where the pharmacist's time in patient-care areas is limited. This concept is currently being practiced at Bayfront Medical Center, and has added a new dimension to the clinical services provided by the pharmacy. It seems likely that detection of therapeutic situations in this manner may be appropriate in other hospital settings.


Author(s):  
Ms Sushmitha ◽  
Ms. Sowmya ◽  
Sushma Rao

<p>Polypharmacy, co-prescribing multiple medication, is implausibly common and infrequently ends up in drug interactions that may have adverse facet effects. Currently, to help doctors in prescribing treatments, clinical call systems fireplace alerts once drug mixtures area unit prescribed that have glorious reactions. Those alerts area unit supported drug interaction severity stored in databases like Lexi-Interact. However, Lexi-Interact severity, that is predicated on clinical trials and literature reviews, doesn't embrace all drug interactions tho' there are several prescribed drug mixtures that haven’t been lined by literature. This paper is enforced by coaching a model that has comparatively high accuracy and recall with glorious Lexi-Interact severity values, the goal would be to check it on drug interactions with glorious severity. Specifically, a drug combine would have a foreseen severity so a panel of clinical pharmacists, people acquainted with clinical outcomes of drug interactions, would rate the validity of that foreseen severity. We intend to realize such reactive medication and report them to the doctors.</p>


Author(s):  
Fivy Kurniawati ◽  
Nanang Munif Yasin ◽  
Amila Dina ◽  
Sanses Atana ◽  
Sarah Nabila Hakim

Adverse Drug Reactions (ADRs) is one of the causes of patient’s prolonged length of stay in the hospital and drug interactions can be included as one of the causes of the cause of ADRs. ADR related to drug interactions is a clinical problem that requires proper prevention. This study aimed to identify potential drug interactions also identify adverse drug reactions (ADRs) related to drug interactions in hospitalized patients at Universitas Gadjah Mada Teaching Hospital. This cross-sectional study used retrospective data collection through patient’s medical records from January to June 2018. Patients included in this study were all patients who received therapy more than two kind of drugs simultaneously treated in hospital wards of Universitas Gadjah Mada Teaching Hospital, Yogyakarta, Indonesia. The data collected were then analyzed descriptively. Drug interactions were analyzed using Drug Interaction Facts 2012 and Stockley. ADRs were analyzed by monitoring documented effects of patients with potential drug interaction. There were 115 of 362 patients (31.8%) with potential drug interactions. The total numbers of potential interactions that occur were 182 interactions. The most potential type of interaction was the interaction with moderate severity, with 115 interactions (63.2%). The majority of drug interactions occur through unknown mechanisms (54.4%). Actual ADR occurs in 3.3% patients who were 2 pediatric patients and 4 geriatric patients. This study can be a reference for drug interactions and ADRs as well as guide for pharmacist and healthcare in providing the right medication.


2019 ◽  
Vol 18 (23) ◽  
pp. 2042-2055 ◽  
Author(s):  
Neeraj Kumar ◽  
Heerak Chugh ◽  
Damini Sood ◽  
Snigdha Singh ◽  
Aarushi Singh ◽  
...  

Heme is central to functions of many biologically important enzymes (hemoproteins). It is an assembly of four porphyrin rings joined through methylene bridges with a central Fe (II). Heme is present in all cells, and its synthesis and degradation balance its amount in the cell. The deregulations of heme networks and incorporation in hemoproteins lead to pathogenic state. This article addresses the detailed structure, biosynthesis, degradation, and transportation associated afflictions to heme. The article is followed by its roles in various diseased conditions where it is produced mainly as the cause of increased hemolysis. It manifests the symptoms in diseases as it is a pro-oxidant, pro-inflammatory and pro-hemolytic agent. We have also discussed the genetic defects that tampered with the biosynthesis, degradation, and transportation of heme. In addition, a brief about the largest hemoprotein group of enzymes- Cytochrome P450 (CYP450) has been discussed with its roles in drug metabolism.


2020 ◽  
Vol 67 (4) ◽  
pp. S69-S78
Author(s):  
Amitesh Gupta ◽  
Vikas Kumar ◽  
Sekar Natarajan ◽  
Rupak Singla

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