Review of Major Drug-Drug Interactions in Thoracic Transplantation

ABSTRACT Doravirine is a novel nonnucleoside reverse transcriptase inhibitor for the treatment of human immunodeficiency virus type 1 infection. In vitro studies were conducted to assess the potential for drug interactions with doravirine via major drug-metabolizing enzymes and transporters. Kinetic studies confirmed that cytochrome P450 3A (CYP3A) plays a major role in the metabolism of doravirine, with ∼20-fold-higher catalytic efficiency for CYP3A4 versus CYP3A5. Doravirine was not a substrate of breast cancer resistance protein (BCRP) and likely not a substrate of organic anion transporting polypeptide 1B1 (OATP1B1) or OATP1B3. Doravirine was not a reversible inhibitor of major CYP enzymes (CYP1A2, -2B6, -2C8, -2C9, -2C19, -2D6, and -3A4) or of UGT1A1, nor was it a time-dependent inhibitor of CYP3A4. No induction of CYP1A2 or -2B6 was observed in cultured human hepatocytes; small increases in CYP3A4 mRNA (≤20%) were reported at doravirine concentrations of ≥10 μM but with no corresponding increase in enzyme activity. In vitro transport studies indicated a low potential for interactions with substrates of BCRP, P-glycoprotein, OATP1B1 and OATP1B3, the bile salt extrusion pump (BSEP), organic anion transporter 1 (OAT1) and OAT3, organic cation transporter 2 (OCT2), and multidrug and toxin extrusion 1 (MATE1) and MATE2K proteins. In summary, these in vitro findings indicate that CYP3A4 and CYP3A5 mediate the metabolism of doravirine, although with different catalytic efficiencies. Clinical trials reported elsewhere confirm that doravirine is subject to drug-drug interactions (DDIs) via CYP3A inhibitors and inducers, but they support the notion that DDIs (either direction) are unlikely via other major drug-metabolizing enzymes and transporters.

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Use of pharmacist integration in oncology clinics to identify and resolve moderate to major drug-drug interactions.

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.31_suppl.71 ◽

2013 ◽

Vol 31 (31_suppl) ◽

pp. 71-71

Author(s):

Jack Toshimine Seki ◽

Matthew Hughsam ◽

Monika Krzyzanowska ◽

Aaron Lo ◽

Pamela Ng ◽

...

Keyword(s):

Drug Interactions ◽

Drug Effects ◽

Medical Problem ◽

Care Providers ◽

Level Of Evidence ◽

Wrong Drug ◽

Survey Results ◽

Major Drug

71 Background: Medication reconciliation (MR) in outpatient clinics has been under-evaluated. We postulated that cancer patients would benefit from MR done by a pharmacist as these patients have many care providers, many medications, and are at high risk of drug-drug interactions (DDIs). Hence, we conducted a quality initiative evaluating the role of a pharmacist in the ambulatory clinics. Methods: One pharmacist prospectively rotated amongst four oncology clinics four days a week from June 3 to September 18, 2008. The pharmacist performed MR, and as a consultant developed therapeutic plans related to drug therapeutic problems (DTPs) including adverse reactions and DDIs. Patient medication lists were retrospectively analyzed using Micromedex and DDIs were categorized by frequency, severity and evidence level. A monthly survey (Likert scale) evaluating pharmacist contributions to each clinic team was completed by physicians and nurses. Results: A total of 158 patients were seen in 227 patient visits. The pharmacist identified 141 DTPs in 60 patients across 74 visits. The most frequently observed were no drug for a medical problem (51.1%), dose too low (12.8%), wrong drug (9.9%), and adverse drug reactions (9.2%). In response, 174 therapeutic plans were made. The most frequently recommended actions were drug added (40.8%), dose changed (13.2%), drug discontinued (9.2%), and interval/duration changed (7.5%). A total of 414 DDIs were identified in 110 patients, across 149 patient visits. On average, 2.62 DDIs were reported per patient, and 1.82 DDIs per visit. By severity, 139 (33.6%) major, 258 (62.3%) moderate, 16 (3.9%) minor and 1 (0.2%) contraindicated DDIs were documented. By level of evidence, 46 (11.1%) DDIs were excellent, and 236 (57%) were good. Survey results showed that doctors and nurses agreed/strongly agreed that pharmacist presence was valuable. The most useful contributions identified were consultation regarding DDIs, adverse drug effects, and medication efficacy decisions. Conclusions: DDI rates are high and most are moderate or major in severity. There is a clear benefit from the integration of a pharmacist to the clinics with an improvement in patient safety and quality of care.

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High rate of major drug–drug interactions of lopinavir–ritonavir for COVID-19 treatment

Scientific Reports ◽

10.1038/s41598-020-78029-3 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Juan Macías ◽

Ana Pinilla ◽

Francisco A. Lao-Dominguez ◽

Anaïs Corma ◽

Enrique Contreras-Macias ◽

...

Keyword(s):

Infectious Diseases ◽

Drug Interactions ◽

High Frequency ◽

Cross Sectional Study ◽

Charlson Index ◽

High Rate ◽

Cross Sectional ◽

Concomitant Medications ◽

The Impact ◽

Major Drug

AbstractThe impact of drug–drug interactions (DDI) between ritonavir-boosted lopinavir (LPV-r) to treat patients with coronavirus disease 2019 (COVID-19) and commonly used drugs in clinical practice is not well-known. Thus, we evaluated the rate and severity of DDI between LPV-r for COVID-19 treatment and concomitant medications. This was a cross-sectional study including all individuals diagnosed of SARS-CoV-2 infection treated with LPV-r and attended at a single center in Southern Spain (March 1st to April 30th, 2020). The frequency [95% confidence interval (95% CI)] of potential and major DDI were calculated. Overall, 469 patients were diagnosed of COVID-19, 125 (27%) of them were prescribed LPV-r. LPV-r had potential DDI with concomitant medications in 97 (78%, 95% CI 69–85%) patients, and in 33 (26%, 95% CI 19–35%) individuals showed major DDI. Twelve (36%) patients with major DDI and 14 (15%) individuals without major DDI died (p = 0.010). After adjustment, only the Charlson index was independently associated with death [adjusted OR (95% CI) for Charlson index ≥ 5: 85 (10–731), p < 0.001]. LPV-r was discontinued due to side effects in 31 (25%) patients. Management by the Infectious Diseases Unit was associated with a lower likelihood of major DDI [adjusted odds ratio (95% CI): 0.14 (0.04–0.53), p = 0.003). In conclusion, a high frequency of DDI between LPV-r for treating COVID-19 and concomitant medications was found, including major DDI. Patients with major DDI showed worse outcomes, but this association was explained by the older age and comorbidities. Patients managed by the Infectious Diseases Unit had lower risk of major DDI.

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THE PREVALENCE OF DRUG–DRUG INTERACTIONS OF PRESCRIPTIONS DISPENSED IN COMMUNITY PHARMACIES IN NAJAF CITY-IRAQ

Asian Journal of Pharmaceutical and Clinical Research ◽

10.22159/ajpcr.2019.v12i9.32960 ◽

2019 ◽

pp. 202-204

Author(s):

SAMER NOORI HASHIM ◽

MOHAMMED JAWAD SALIH AL-HAIDAREY

Keyword(s):

Internal Medicine ◽

Drug Interactions ◽

General Practitioners ◽

Screening Program ◽

General Surgeon ◽

Community Pharmacies ◽

Vital Function ◽

Computerized Screening ◽

Major Drug

Objectives: The main objectives of this work were to estimate the frequency, type, and nature of possible drug–drug interactions in prescriptions dispensed from community pharmacies in Al-Najaf city, secondary objectives were the study of the association between specialty of physicians and the rate of recurrence of drug–drug interactions and to determine medication classes, which were involved in possible drug–drug interactions. Methods: To investigate this study, 211 prescriptions dispensed in three community pharmacies in Al-Najaf city were collected and by the computerized screening program to identify drug–drug interactions. Results: The results showed that the total number of interactions was recognized to be 41% of all prescriptions with the prevalence of major drug– drug interactions was 14%, minor was 16%, and moderate was 70%. Conclusions: This study concluded that most identified drug–drug interactions were recognized in prescriptions written by an internal medicine specialist, orthopedics, general practitioners, an ear-nose-throat specialist, and general surgeon. The ratio of drug–drug interactions/number of prescriptions increased with increasing the number of drugs prescribed per patient (r=0.93, regression p<0.05). This study suggested that the role of the pharmacist should be moved from medication-oriented to patient-oriented, and the clinical pharmacists should have a vital function in recognizing and avoiding drug–drug interactions in prescriptions dispensed to patients.

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Major drug interactions

The ESC Handbook on Cardiovascular Pharmacotherapy ◽

10.1093/med/9780198759935.003.0023 ◽

2019 ◽

pp. 387-410

Author(s):

Maja Hellfritzsch Poulsen ◽

Marlene Lunddal Krogh

Keyword(s):

Side Effects ◽

Drug Interactions ◽

Clinical Work ◽

Cardiovascular Drugs ◽

Close Monitoring ◽

Pharmacodynamic Interactions ◽

Vulnerable Patients ◽

Major Drug ◽

Important Drug ◽

Dose Reductions

Drug interactions are commonly present in our daily clinical work and have the ability to either enhance or reduce the effects of a drug, but also, just as importantly, decrease or increase the risk of side effects, thereby increasing the risk of toxicity. This chapter will focus on the clinically important drug–drug interactions with some of the most often used cardiovascular drugs and especially where there is a risk of causing harm to patients due to serious side effects. Both pharmacokinetic and pharmacodynamic interactions will be discussed, with focus on the most vulnerable patients. In some cases, drug combinations are contraindicated, whereas in other cases, the combinations can be used with, for example, close monitoring or dose reductions, but most importantly, the risk of interactions should be considered in order to take appropriate precautions upfront.

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ASSESSMENT OF DRUG USE FOR INPATIENTS WHO WERE PRESCRIBED CEFTAZIDIME: A RETROSPECTIVE CROSS-SECTIONAL STUDY IN A DISTRICT-LEVEL HOSPITAL

Tạp chí Y học Việt Nam ◽

10.51298/vmj.v506i1-2.977 ◽

2021 ◽

Vol 506 (1-2) ◽

Author(s):

Nguyen Thi Thanh Huong ◽

Dinh Xuan Dai

Keyword(s):

Drug Use ◽

Drug Interactions ◽

Medical Records ◽

Cross Sectional Study ◽

District Level ◽

Sectional Study ◽

Broad Spectrum Antibiotic ◽

Cross Sectional ◽

Level Hospital ◽

Major Drug

In health facilities, there is a lot of public concern about the irrational use of medications, especially antibiotic misuse. This retrospective cross-sectional study was conducted to assess the utilization of medicines for inpatients using ceftazidime in treatment in a district-level hospital in Vietnam, using 396 medical records. The results showed that there were approximately 6.7 kinds of drugs prescribed for each inpatient, including roughly 1.23 antibiotics. On average, 5.69 days of hospitalization cost an inpatient about 74.31USD, including more than 20USD for medicines (9.22USD for antibiotics) and 54.27USD for other expenses. There were 19.70% of medical records in which found at least one drug-drug interaction. Cardiovascular medicines, corticoids, fluoroquinolones and proton-pump inhibitors were medicine groups involving many found drug-drug interactions. For ceftazidime, indications of this antibiotic were inappropriate for nearly half of inpatients. For 199 inpatients whose indications’ ceftazidime were appropriate, the route of ceftazidime administration was appropriate but its dose per day and dose duration were inappropriate. More importantly, ceftazidime was used with a dosage lower than the recommended dosage (98.99%). In conclusion, there were several problems involving drug use that should be addressed, including curbing major drug-drug interactions and the irrational use of ceftazidime, a watch-group, broad-spectrum antibiotic.

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High rate of major drug-drug interactions of lopinavir-ritonavir for COVID-19 treatment

10.1101/2020.07.30.20165027 ◽

2020 ◽

Author(s):

Juan Macias ◽

Ana Pinilla ◽

Francisco A Lao-Dominguez ◽

Anais Corma ◽

Enrique Contreras-Macias ◽

...

Keyword(s):

Infectious Diseases ◽

Drug Interactions ◽

High Frequency ◽

Cross Sectional Study ◽

Charlson Index ◽

High Rate ◽

Cross Sectional ◽

Concomitant Medications ◽

The Impact ◽

Major Drug

The impact of drug-drug interactions (DDI) between ritonavir-boosted lopinavir (LPV-r) to treat patients with coronavirus disease 2019 (COVID-19) and commonly used drugs in clinical practice is not well-known. Thus, we evaluated the rate and severity of DDI between LPV-r for COVID-19 treatment and concomitant medications. This was a cross-sectional study including all individuals diagnosed of SARS-CoV-2 infection treated with LPV-r and attended at a single center in Southern Spain (March 1st to April 30th, 2020). The frequency [95% confidence interval (95% CI)] of potential and major DDI were calculated. Overall, 469 patients were diagnosed of COVID-19, 125 (27%) of them were prescribed LPV-r. LPV-r had potential DDI with concomitant medications in 97 (78%, 95% CI: 69%-85%) patients, and in 33 (26%, 95% CI: 19%-35%) individuals showed major DDI. Twelve (36%) patients with major DDI and 14 (15%) individuals without major DDI died (p=0.010). After adjustment, only the Charlson index was independently associated with death [adjusted OR (95% CI) for Charlson index ≥5: 85 (10-731), p <0.001]. LPV-r was discontinued due to side effects in 31 (25%) patients. Management by the Infectious Diseases Unit was associated with a lower likelihood of major DDI [adjusted odds ratio (95% CI): 0.14 (0.04-0.53), p=0.003). In conclusion, a high frequency of DDI between LPV-r for treating COVID-19 and concomitant medications was found, including major DDI. Patients with major DDI showed worse outcomes, but this association was explained by the older age and comorbidities. Patients managed by the Infectious Diseases Unit had lower risk of major DDI.

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Major drug interactions

The ESC Handbook on Cardiovascular Pharmacotherapy ◽

10.1093/med/9780198759935.003.0023_update_001 ◽

2019 ◽

pp. 387-410

Author(s):

Maja Hellfritzsch Poulsen ◽

Marlene Lunddal Krogh

Keyword(s):

Side Effects ◽

Drug Interactions ◽

Clinical Work ◽

Cardiovascular Drugs ◽

Close Monitoring ◽

Pharmacodynamic Interactions ◽

Vulnerable Patients ◽

Major Drug ◽

Important Drug ◽

Dose Reductions

Drug interactions are commonly present in our daily clinical work and have the ability to either enhance or reduce the effects of a drug, but also, just as importantly, decrease or increase the risk of side effects, thereby increasing the risk of toxicity. This chapter will focus on the clinically important drug–drug interactions with some of the most often used cardiovascular drugs and especially where there is a risk of causing harm to patients due to serious side effects. Both pharmacokinetic and pharmacodynamic interactions will be discussed, with focus on the most vulnerable patients. In some cases, drug combinations are contraindicated, whereas in other cases, the combinations can be used with, for example, close monitoring or dose reductions, but most importantly, the risk of interactions should be considered in order to take appropriate precautions upfront.

Download Full-text