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1.
Pharmacol Res Perspect ; 10(1): e00909, 2022 02.
Article in English | MEDLINE | ID: covidwho-1588891

ABSTRACT

The novel coronavirus disease 2019 (COVID-19) emerged in late December 2019 in china and has rapidly spread to many countries around the world. The effective pharmacotherapy can reduce the mortality of COVID-19. Antiviral medications are the candidate therapies for the management of COVID-19. Molnupiravir is an antiviral drug with anti-RNA polymerase activity and currently is under investigation for the treatment of patients with COVID-19. This review focuses on summarizing published literature for the mechanism of action, safety, efficacy, and clinical trials of molnupiravir in the treatment of COVID-19 patients.


Subject(s)
Antiviral Agents/therapeutic use , COVID-19/drug therapy , Cytidine/analogs & derivatives , Hydroxylamines/therapeutic use , COVID-19/virology , Clinical Trials as Topic , Cytidine/therapeutic use , Drug Interactions , Humans , SARS-CoV-2/isolation & purification
2.
Int J Environ Res Public Health ; 18(21)2021 11 08.
Article in English | MEDLINE | ID: covidwho-1512319

ABSTRACT

Pandemic of coronavirus disease (COVID-19) is still pressing the healthcare systems worldwide. Thus far, the lack of available COVID-19-targeted treatments has led scientists to look through drug repositioning practices and exploitation of available scientific evidence for potential efficient drugs that may block biological pathways of SARS-CoV-2. Till today, several molecules have emerged as promising pharmacological agents, and more than a few medication protocols are applied during hospitalization. On the other hand, given the criticality of the disease, it is important for healthcare providers, especially those in COVID-19 clinics (i.e., nursing personnel and treating physicians), to recognize potential drug interactions that may lead to adverse drug reactions that may negatively impact the therapeutic outcome. In this review, focusing on patients with respiratory diseases (i.e., asthma or chronic obstructive pulmonary disease) that are treated also for COVID-19, we discuss possible drug interactions, their underlying pharmacological mechanisms, and possible clinical signs that healthcare providers in COVID-19 clinics may need to acknowledge as adverse drug reactions due to drug-drug interactions.


Subject(s)
COVID-19 , Respiration Disorders , Drug Interactions , Humans , Pandemics , SARS-CoV-2
3.
Eur J Pharmacol ; 904: 174143, 2021 Aug 05.
Article in English | MEDLINE | ID: covidwho-1487708

ABSTRACT

Disulfiram (DSF) is a well-known anti-alcohol agent that inhibits aldehyde dehydrogenase and results in extreme 'hangover' symptoms when consumed with alcohol. This drug, however, has been suggested as useful in other forms of drug addiction due to its beneficial potential in both drug abuse reduction and withdrawal. However, among other drugs used in alcohol dependence, it carries the greatest risk of pharmacological interactions. Concomitant use of DSF and central nervous system stimulants usually leads to harmful, undesirable effects. To date, there is still limited data regarding the detailed safety profile of DSF as a concomitant drug. In this review article, we outline the current state of knowledge about DSF, its broad pharmacological action, as well as therapeutic effects, with a particular emphasis on the molecular understanding of its potential pharmacodynamic interactions with common addictive substances (e.g., alcohol, cocaine, cannabinoids, opioids) supported by relevant examples.


Subject(s)
Acetaldehyde Dehydrogenase Inhibitors/pharmacology , Acetaldehyde Dehydrogenase Inhibitors/therapeutic use , Disulfiram/pharmacology , Disulfiram/therapeutic use , Substance-Related Disorders/drug therapy , Alcohol Drinking/prevention & control , Alcoholism/drug therapy , Animals , Disulfiram/adverse effects , Drug Interactions , Humans
4.
Drug Saf ; 43(7): 657-660, 2020 07.
Article in English | MEDLINE | ID: covidwho-1482335

ABSTRACT

INTRODUCTION: Hydroxychloroquine was recently promoted in patients infected with COVID-19 infection. A recent experimental study has suggested an increased toxicity of hydroxychloroquine in association with metformin in mice. OBJECTIVE: The present study was undertaken to investigate the reality of this putative drug-drug interaction between hydroxychloroquine and metformin using pharmacovigilance data. METHODS: Using VigiBase®, the WHO pharmacovigilance database, we performed a disproportionality analysis (case/non-case study). Cases were reports of fatal outcomes with the drugs of interest and non-cases were all other reports for these drugs registered between 1 January 2000 and 31 December 2019. Data with hydroxychloroquine (or metformin) alone were compared with the association hydroxychloroquine + metformin. Results are reported as ROR (reporting odds ratio) with their 95% confidence interval. RESULTS: Of the 10,771 Individual Case Safety Reports (ICSR) involving hydroxychloroquine, 52 were recorded as 'fatal outcomes'. In comparison with hydroxychloroquine alone, hydroxychloroquine + metformin was associated with an ROR value of 57.7 (23.9-139.3). In comparison with metformin alone, hydroxychloroquine + metformin was associated with an ROR value of 6.0 (2.6-13.8). CONCLUSION: Our study identified a signal for the association hydroxychloroquine + metformin that appears to be more at risk of fatal outcomes (particularly by completed suicides) than one of the two drugs when given alone.


Subject(s)
Coronavirus Infections , Drug Interactions , Drug Therapy, Combination , Hydroxychloroquine , Metformin , Pandemics , Pneumonia, Viral , Adult , Adverse Drug Reaction Reporting Systems/statistics & numerical data , Betacoronavirus/isolation & purification , COVID-19 , Coronavirus Infections/diagnosis , Coronavirus Infections/drug therapy , Coronavirus Infections/epidemiology , Drug Therapy, Combination/adverse effects , Drug Therapy, Combination/mortality , Female , Humans , Hydroxychloroquine/pharmacokinetics , Hydroxychloroquine/therapeutic use , Hypoglycemic Agents/pharmacokinetics , Hypoglycemic Agents/therapeutic use , Male , Metformin/pharmacokinetics , Metformin/therapeutic use , Middle Aged , Pharmacovigilance , Pneumonia, Viral/diagnosis , Pneumonia, Viral/drug therapy , Pneumonia, Viral/epidemiology , SARS-CoV-2
5.
J Infect Dev Ctries ; 15(9): 1273-1276, 2021 09 30.
Article in English | MEDLINE | ID: covidwho-1478140

ABSTRACT

INTRODUCTION: An outbreak of coronavirus disease-19 (COVID-19) has occurred in different parts of the world. Although a large piece of information regarding the epidemiology, clinical features, and management of COVID-19 has been reported in the general population, there is very limited data regarding organ transplant recipients, particularly regarding the management of maintenance immunosuppressive agents during infection. METHODOLOGY: We described a case of kidney transplant recipient from Thailand who had COVID-19 pneumonia and severe acute kidney injury. RESULTS: The patient's serum creatinine peaked at 7.0 mg/dL on day 15 of illness and returned to baseline value of 2.0 mg/dL on day 26 of illness. We have shown how we modified tacrolimus, mycophenolate, and steroids in the patient who had received favipiravir and lopinavir/ritonavir for COVID-19 pneumonia. CONCLUSIONS: In this case, successful modification of this immunosuppressive regimen was accomplished to reduce drug interaction complications, aiming to avoid calcineurin inhibitor nephrotoxicity while maintaining appropriate levels of immunosuppression to prevent organ rejection and to promote the patient's recovery from infection.


Subject(s)
Acute Kidney Injury/virology , COVID-19/drug therapy , Immunosuppressive Agents/administration & dosage , Acute Kidney Injury/drug therapy , Adult , Amides/therapeutic use , Drug Combinations , Drug Interactions , Humans , Kidney Transplantation , Lopinavir/therapeutic use , Male , Mycophenolic Acid/administration & dosage , Pyrazines/therapeutic use , Ritonavir/therapeutic use , Steroids/administration & dosage , Tacrolimus/administration & dosage , Thailand , Transplant Recipients
6.
Ann Med ; 53(1): 1673-1675, 2021 12.
Article in English | MEDLINE | ID: covidwho-1437738

ABSTRACT

In the setting of the raging COVID-19 pandemic, the search for innovative therapeutics is desperately sought after. As we learn more about the characteristics and metabolic health of patients and as our understanding of COVID-19 pathophysiology and treatment progresses, so is our understanding of medication effects that might increase disease severity. As of late, ACE inhibitors have been under investigation for a potential increase in illness severity due to ACE2 upregulation. Given our knowledge of other nutrient-pharmaceutical interactions, could the ACE inhibitor impact on COVID be due to something else? In this paper, we discuss the possibility that ACE inhibitors might be affecting COVID-19 patients by causing zinc insufficiency.KEY MESSAGESZinc deficiency caused by chronic ACE inhibitor usage may exacerbate the pathogenicity of COVID-19 in susceptible patients.A multi-center study is needed to assess the zinc levels of patients with COVID-19 who are taking ACE inhibitors and other medications that may result in low zinc levels.


Subject(s)
Angiotensin-Converting Enzyme 2/metabolism , Angiotensin-Converting Enzyme Inhibitors/adverse effects , COVID-19/drug therapy , Zinc/deficiency , Angiotensin-Converting Enzyme 2/drug effects , Angiotensin-Converting Enzyme Inhibitors/administration & dosage , Angiotensin-Converting Enzyme Inhibitors/therapeutic use , COVID-19/diagnosis , COVID-19/epidemiology , COVID-19/virology , Drug Interactions , Female , Humans , Male , Nutritional Status/drug effects , Pharmaceutical Preparations , Risk Factors , SARS-CoV-2/genetics , Severity of Illness Index , Zinc/blood
7.
J Virol Methods ; 298: 114283, 2021 12.
Article in English | MEDLINE | ID: covidwho-1428226

ABSTRACT

The SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) is essential for virus replication, therefore it is a promising drug target. Here we present a surface plasmon resonance approach to study the interaction of RdRp with drugs in real time. We monitored the effect of favipiravir, ribavirin, sofosbuvir triphosphate PSI-7409 and suramin on RdRp binding to RNA immobilized on the chip. Suramin precluded interaction of RdRp with RNA and even displaced RdRp from RNA.


Subject(s)
COVID-19 , RNA-Dependent RNA Polymerase , Antiviral Agents/pharmacology , Drug Interactions , Humans , RNA, Viral , SARS-CoV-2 , Suramin/pharmacology , Surface Plasmon Resonance
8.
Proc Natl Acad Sci U S A ; 118(39)2021 09 28.
Article in English | MEDLINE | ID: covidwho-1412708

ABSTRACT

Effective treatments for COVID-19 are urgently needed. However, discovering single-agent therapies with activity against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been challenging. Combination therapies play an important role in antiviral therapies, due to their improved efficacy and reduced toxicity. Recent approaches have applied deep learning to identify synergistic drug combinations for diseases with vast preexisting datasets, but these are not applicable to new diseases with limited combination data, such as COVID-19. Given that drug synergy often occurs through inhibition of discrete biological targets, here we propose a neural network architecture that jointly learns drug-target interaction and drug-drug synergy. The model consists of two parts: a drug-target interaction module and a target-disease association module. This design enables the model to utilize drug-target interaction data and single-agent antiviral activity data, in addition to available drug-drug combination datasets, which may be small in nature. By incorporating additional biological information, our model performs significantly better in synergy prediction accuracy than previous methods with limited drug combination training data. We empirically validated our model predictions and discovered two drug combinations, remdesivir and reserpine as well as remdesivir and IQ-1S, which display strong antiviral SARS-CoV-2 synergy in vitro. Our approach, which was applied here to address the urgent threat of COVID-19, can be readily extended to other diseases for which a dearth of chemical-chemical combination data exists.


Subject(s)
Antiviral Agents/pharmacology , COVID-19/drug therapy , Deep Learning , Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , Cell Survival/drug effects , Drug Combinations , Drug Interactions , Drug Synergism , Humans , SARS-CoV-2
9.
Mol Pharmacol ; 100(6): 548-557, 2021 12.
Article in English | MEDLINE | ID: covidwho-1403004

ABSTRACT

Equilibrative nucleoside transporters (ENTs) are present at the blood-testis barrier (BTB), where they can facilitate antiviral drug disposition to eliminate a sanctuary site for viruses detectable in semen. The purpose of this study was to investigate ENT-drug interactions with three nucleoside analogs, remdesivir, molnupiravir, and molnupiravir's active metabolite, ß-d-N4-hydroxycytidine (EIDD-1931), and four non-nucleoside molecules repurposed as antivirals for coronavirus disease 2019 (COVID-19). The study used three-dimensional pharmacophores for ENT1 and ENT2 substrates and inhibitors and Bayesian machine learning models to identify potential interactions with these transporters. In vitro transport experiments demonstrated that remdesivir was the most potent inhibitor of ENT-mediated [3H]uridine uptake (ENT1 IC50: 39 µM; ENT2 IC50: 77 µM), followed by EIDD-1931 (ENT1 IC50: 259 µM; ENT2 IC50: 467 µM), whereas molnupiravir was a modest inhibitor (ENT1 IC50: 701 µM; ENT2 IC50: 851 µM). Other proposed antivirals failed to inhibit ENT-mediated [3H]uridine uptake below 1 mM. Remdesivir accumulation decreased in the presence of 6-S-[(4-nitrophenyl)methyl]-6-thioinosine (NBMPR) by 30% in ENT1 cells (P = 0.0248) and 27% in ENT2 cells (P = 0.0054). EIDD-1931 accumulation decreased in the presence of NBMPR by 77% in ENT1 cells (P = 0.0463) and by 64% in ENT2 cells (P = 0.0132), which supported computational predictions that both are ENT substrates that may be important for efficacy against COVID-19. NBMPR failed to decrease molnupiravir uptake, suggesting that ENT interaction is likely inhibitory. Our combined computational and in vitro data can be used to identify additional ENT-drug interactions to improve our understanding of drugs that can circumvent the BTB. SIGNIFICANCE STATEMENT: This study identified remdesivir and EIDD-1931 as substrates of equilibrative nucleoside transporters 1 and 2. This provides a potential mechanism for uptake of these drugs into cells and may be important for antiviral potential in the testes and other tissues expressing these transporters.


Subject(s)
Adenosine Monophosphate/analogs & derivatives , Alanine/analogs & derivatives , Antiviral Agents/metabolism , Cytidine/analogs & derivatives , Equilibrative Nucleoside Transporter 1/metabolism , Equilibrative-Nucleoside Transporter 2/metabolism , SARS-CoV-2/metabolism , Adenosine Monophosphate/administration & dosage , Adenosine Monophosphate/metabolism , Alanine/administration & dosage , Alanine/metabolism , Antiviral Agents/administration & dosage , COVID-19/drug therapy , COVID-19/metabolism , Cytidine/administration & dosage , Cytidine/metabolism , Dose-Response Relationship, Drug , Drug Interactions/physiology , HeLa Cells , Humans , Protein Binding/drug effects , Protein Binding/physiology , SARS-CoV-2/drug effects
11.
Int J Mol Sci ; 22(17)2021 Sep 03.
Article in English | MEDLINE | ID: covidwho-1390658

ABSTRACT

Anti-epileptic drugs (AEDs) are an important group of drugs of several generations, ranging from the oldest phenobarbital (1912) to the most recent cenobamate (2019). Cannabidiol (CBD) is increasingly used to treat epilepsy. The outbreak of the SARS-CoV-2 pandemic in 2019 created new challenges in the effective treatment of epilepsy in COVID-19 patients. The purpose of this review is to present data from the last few years on drug-drug interactions among of AEDs, as well as AEDs with other drugs, nutrients and food. Literature data was collected mainly in PubMed, as well as google base. The most important pharmacokinetic parameters of the chosen 29 AEDs, mechanism of action and clinical application, as well as their biotransformation, are presented. We pay a special attention to the new potential interactions of the applied first-generation AEDs (carbamazepine, oxcarbazepine, phenytoin, phenobarbital and primidone), on decreased concentration of some medications (atazanavir and remdesivir), or their compositions (darunavir/cobicistat and lopinavir/ritonavir) used in the treatment of COVID-19 patients. CBD interactions with AEDs are clearly defined. In addition, nutrients, as well as diet, cause changes in pharmacokinetics of some AEDs. The understanding of the pharmacokinetic interactions of the AEDs seems to be important in effective management of epilepsy.


Subject(s)
Anticonvulsants/therapeutic use , COVID-19/drug therapy , Cannabidiol/therapeutic use , Drug Interactions , Nutrients/metabolism , Anticonvulsants/chemistry , Anticonvulsants/pharmacokinetics , COVID-19/virology , Cannabidiol/chemistry , Cannabidiol/pharmacokinetics , Carbamazepine/chemistry , Carbamazepine/pharmacokinetics , Carbamazepine/therapeutic use , Clobazam/chemistry , Clobazam/pharmacokinetics , Clobazam/therapeutic use , Epilepsy/drug therapy , Epilepsy/pathology , Humans , SARS-CoV-2/isolation & purification
14.
BMJ Open Gastroenterol ; 8(1)2021 05.
Article in English | MEDLINE | ID: covidwho-1388491
15.
Eur J Clin Invest ; 51(7): e13604, 2021 Jul.
Article in English | MEDLINE | ID: covidwho-1388253

ABSTRACT

BACKGROUND: There is a concern that influenza vaccination may increase the incidence of immune-related adverse events in patients receiving immune checkpoint inhibitors (ICIs). The aim of this systematic review was to summarize the available data on the safety and efficacy of influenza vaccination in cancer patients receiving ICIs. METHODS: Studies reporting safety and efficacy outcomes of influenza vaccination in cancer patients receiving ICIs were included. Only descriptive statistics were conducted to obtain a pooled rate of immune-related adverse events in vaccinated patients. RESULTS: Ten studies assessing the safety and eight assessing the efficacy of influenza vaccination in cancer patients receiving ICIs were identified, for a total of 1124 and 986 vaccinated patients, respectively. Most patients had melanoma or lung cancer and received a single agent anti-PD-1, but also other tumour types and immunotherapy combinations were represented. No severe vaccination-related toxicities were reported. The pooled incidence of any grade immune checkpoint inhibitor-related adverse events was 28.9%. In the 6 studies specifying the incidence of grade 3-4 toxicities, the pooled incidence was 7.5%. No grade 5 toxicities were reported. No pooled descriptive analysis was conducted in studies reporting efficacy outcomes due to the heterogeneity of endpoints and data reporting. Nevertheless, among the eight studies included, seven reported positive efficacy outcomes of influenza vaccination. CONCLUSION: The results of this systematic review support the safety and efficacy of influenza vaccination in cancer patients receiving ICIs. These results are particularly relevant in the context of the SARS-CoV-2 pandemic.


Subject(s)
Immune Checkpoint Inhibitors/adverse effects , Influenza Vaccines/therapeutic use , Influenza, Human/prevention & control , Neoplasms/drug therapy , COVID-19 , Case-Control Studies , Drug Interactions , Humans , Immune Checkpoint Inhibitors/therapeutic use , Immunogenicity, Vaccine , Influenza, Human/epidemiology , SARS-CoV-2
17.
J Clin Pharmacol ; 61 Suppl 2: S129-S141, 2021 08.
Article in English | MEDLINE | ID: covidwho-1355875

ABSTRACT

Use of US Food and Drug Administration-approved substances of abuse has innate risks due to pharmacologic and pharmacokinetic properties of the medications, but the risk when using nonapproved drug products is much greater. Unbeknownst to the user, the dose of active ingredients in substances of abuse can vary substantially between different products because of manufacturing practices or improper storage. Even naturally occurring substances of abuse can have extensive dosage variability because of effects of the growing season and conditions, or differences in harvesting, storage, or manufacture of the finished products. Many illicit substances are adulterated, to make up for intentional underdosing or to enhance the effect of the intended active ingredient. These adulterants can be dangerous and produce direct cardiovascular, neurologic, hematologic, or dermatologic reactions or obscure adverse effects. Finally, an illicit substance can be contaminated or substituted for another one during its manufacture, leading to differences in adverse events, adverse event severity, or the drug interaction profile. Substances can be contaminated with microbes that induce infections or heavy metals that can damage organs or cause cancer. This milieu of undisclosed substances can also induce drug interactions. For reasons that are discussed, individuals who use substances of abuse are at increased risk of morbidity or mortality if they develop coronavirus disease 2019. Health professionals who treat patients with acute, urgent events associated with substances of abuse, or those treating the chronic manifestations of addiction, need to appreciate the complex and variable composition of substances of abuse and their potential health effects.


Subject(s)
Drug-Related Side Effects and Adverse Reactions/complications , Illicit Drugs/adverse effects , Substance-Related Disorders/complications , COVID-19/mortality , Drug Interactions/physiology , Drug-Related Side Effects and Adverse Reactions/mortality , Humans , Substance-Related Disorders/mortality , United States , United States Food and Drug Administration
18.
Expert Rev Hematol ; 14(9): 819-830, 2021 09.
Article in English | MEDLINE | ID: covidwho-1349725

ABSTRACT

INTRODUCTION: Ibrutinib is a highly effective drug for patients with chronic lymphocytic leukemia (CLL), and is well tolerated even by older patients and those unfit to receive conventional immuno-chemotherapy. AREAS COVERED: The occurrence of adverse events was revealed as a major cause of ibrutinib failure in the real-world. Ibrutinib-induced lymphocytosis carries the risk of an untimely interruption of therapy because it may be misinterpreted as disease progression. In addition, drug interactions can worsen ibrutinib-associated toxicities by increasing the plasma concentration of ibrutinib. In this review, we present a case of major hemorrhage and atrial fibrillation (AF) during ibrutinib use and summarize the adverse events associated with ibrutinib. Furthermore, the practical management of ibrutinib-associated toxicities was covered with reference to a drug interaction mechanism. EXPERT OPINION: Clinicians should examine the prescribed drugs prior to ibrutinib initiation and carefully monitor toxicities while taking ibrutinib. A reduced dose of ibrutinib with the concurrent use of CYP3A inhibitors such as antifungal agents could be an attractive strategy to reduce toxicities and may confer financial benefits. Reducing unexpected toxicities is as significant as achieving treatment response in the era of life-long therapy with ibrutinib in patients with CLL.


Subject(s)
Adenine/analogs & derivatives , Leukemia, Lymphocytic, Chronic, B-Cell/drug therapy , Piperidines/therapeutic use , Protein Kinase Inhibitors/therapeutic use , Adenine/adverse effects , Adenine/pharmacology , Adenine/therapeutic use , Aged , COVID-19/complications , Disease Management , Drug Interactions , Drug-Related Side Effects and Adverse Reactions/etiology , Drug-Related Side Effects and Adverse Reactions/therapy , Humans , Leukemia, Lymphocytic, Chronic, B-Cell/complications , Male , Piperidines/adverse effects , Piperidines/pharmacology , Protein Kinase Inhibitors/adverse effects , Protein Kinase Inhibitors/pharmacology
19.
Int J Clin Pract ; 75(11): e14710, 2021 Nov.
Article in English | MEDLINE | ID: covidwho-1348135

ABSTRACT

AIMS: Hydroxychloroquine (HCQ) is using as a repurposed drug in considerable proportion of COVID-19 patients. However, being a substrate of cytochrome P450 (CYP) enzymes of CYP3A4/5, CYP2C8 and CYP2D6, the safety and efficacy of this drug may be affected by the coadministration of respective CYP inhibitors, substrates or inducer drugs. It was aimed to identify potential clinically significant drug-drug interaction (DDI) pairs of HCQ. METHODS: Inhibitors, substrates and inducer drugs lists of CYP enzymes of interest from international well-recognised evidence-based drug interaction resources were used to identify potential clinically significant pharmacokinetic DDI pairs of HCQ. RESULTS: Among 329 identified interacting drugs that predicted to cause clinically significant DDIs of HCQ, 45 (13.7%), 43 (13.1%) and 123 (37.4%) unique DDI pairs were identified from the FDA, Stockley's and Flockhart lists, respectively. Of interest, 55 (16.7%) DDI pairs were recognised by all three resources. At least, 29 (8.8%) severe DDI pairs were identified predicted to cause severe toxicity of HCQ in patients with COVID-19. When comparing these interactions with Liverpool DDI lists, it was found that out of 423 total interactions, 238 (56.3%) and 94 (22.2%) unique DDI pairs were identified from all three resources and Liverpool DDI lists, respectively. Of interest, only three (0.7%) DDI pairs were recognised by both the three international resources and Liverpool DDI lists of HCQ. CONCLUSION: Using HCQ has clinical debate whether it should or should not continue in COVID-19 patients, however, potential clinically significant DDIs identified in this study may optimise safety or efficacy of HCQ in considerable proportion of patients.


Subject(s)
COVID-19 , Hydroxychloroquine , COVID-19/drug therapy , Drug Interactions , Humans , Hydroxychloroquine/adverse effects
20.
Eur Rev Med Pharmacol Sci ; 25(14): 4854-4867, 2021 07.
Article in English | MEDLINE | ID: covidwho-1335543

ABSTRACT

OBJECTIVE: The purpose of this narrative review is to discuss the available information regarding the currently utilized COVID-19 therapies (and the evidence level supporting them) and opioids for chronic pain with a focus on warnings of potential interactions between these two therapeutic approaches. MATERIALS AND METHODS: Papers were retrieved from a PubMed search, using different combinations of keywords [e.g., pain treatment AND COVID-19 AND drug-drug interaction (DDI)], without limitations in terms of publication date and language. RESULTS: Remdesivir is an inhibitor of CYP3A4 and may increase the plasma concentration of CYP3A4 substrates (e.g., fentanyl). Dexamethasone is an inducer of CYP3A4 and glycoprotein P, thus coadministration with drugs metabolized by this isoform will lead to their increased clearance. Dexamethasone may cause hypokalemia, thus potentiating the risk of ventricular arrhythmias if it is given with opioids able to prolong the QT interval, such as oxycodone and methadone. Finally, the existing differences among opioids with regard to their impact on immune responses should also be taken into account with only tapentadol and hydromorphone appearing neutral on both cytokine production and immune parameters. CONCLUSIONS: Clinicians should keep in mind the frequent DDIs with drugs extensively metabolized by the CYP450 system and prefer opioids undergoing a limited hepatic metabolism. Identification and management of DDIs and dissemination of the related knowledge should be a major goal in the delivery of chronic care to ensure optimized patient outcomes and facilitate updating recommendations for COVID-19 therapy in frail populations, namely comorbid, poly-medicated patients or individuals suffering from substance use disorder.


Subject(s)
Analgesics, Opioid/therapeutic use , COVID-19/drug therapy , Chronic Pain/drug therapy , SARS-CoV-2 , Adenosine Monophosphate/analogs & derivatives , Adenosine Monophosphate/therapeutic use , Alanine/analogs & derivatives , Alanine/therapeutic use , Anti-Inflammatory Agents/therapeutic use , Antiviral Agents/therapeutic use , Dexamethasone/therapeutic use , Drug Interactions , Humans
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