CredibleMeds

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CredibleMeds is an online database launched in 2009 of information regarding serious drug-drug interactions associated with QT prolongation or the potentially lethal arrhythmia, torsades de pointes (TdP). [1] [2] [3] [4] [5] [6] It also assists with measurement of the quality of healthcare delivery for the Centers for Medicare and Medicaid Services, and aids in the management of patients with inherited channelopathies. [7] [8]

Contents

The overall goal of CredibleMeds is to support efforts to improve the safe use of medicines.

History

The Arizona Center for Education and Research on Therapeutics (AZCERT) maintains the CredibleMeds database. Founded in 2000 at the University of Arizona as part of a network of 14 federally-funded CERTs, [9] AZCERT became a separate non-profit corporation in 2012 funded by the US Food and Drug Administration (FDA), research grants, and charitable contributions. AZCERT focuses on drugs and drug–drug interactions, especially those that cause QT prolongation and Torsades de Pointes (TdP) arrhythmia, and provides its research and its lists of drugs [10] free of charge to the public, healthcare providers, and researchers for personal, professional, and non-commercial purposes. To maintain the independence of its work, AZCERT does not receive funding from companies that have a commercial interest in medications.

Adverse drug event analysis

AZCERT developed the Adverse Drug Event Causality Analysis (ADECA) to evaluate drugs for their risk of causing QT prolongation and TdP. [11] As part of its ADECA reviews, AZCERT includes drugs marketed outside the United States, especially in Europe, Japan, and Canada. In addition to their use to inform healthcare decision-making, CredibleMeds’ lists of drugs have been used in research published in more than 50 scientific articles. [12] [13] [14] [15]

Related Research Articles

<span class="mw-page-title-main">Clarithromycin</span> Antibiotic medication

Clarithromycin, sold under the brand name Biaxin among others, is an antibiotic used to treat various bacterial infections. This includes strep throat, pneumonia, skin infections, H. pylori infection, and Lyme disease, among others. Clarithromycin can be taken by mouth as a pill or liquid.

<span class="mw-page-title-main">Pimozide</span> Chemical compound

Pimozide is an antipsychotic drug of the diphenylbutylpiperidine class. It was discovered at Janssen Pharmaceutica in 1963. It has a high potency compared to chlorpromazine. On a weight basis it is even more potent than haloperidol. It also has special neurologic indications for Tourette syndrome and resistant tics. The side effects include akathisia, tardive dyskinesia, and, more rarely, neuroleptic malignant syndrome and prolongation of the QT interval.

<span class="mw-page-title-main">Long QT syndrome</span> Medical condition

Long QT syndrome (LQTS) is a condition affecting repolarization (relaxing) of the heart after a heartbeat, giving rise to an abnormally lengthy QT interval. It results in an increased risk of an irregular heartbeat which can result in fainting, drowning, seizures, or sudden death. These episodes can be triggered by exercise or stress. Some rare forms of LQTS are associated with other symptoms and signs including deafness and periods of muscle weakness.


Antiarrhythmic agents, also known as cardiac dysrhythmia medications, are a group of pharmaceuticals that are used to suppress abnormally fast rhythms (tachycardias), such as atrial fibrillation, supraventricular tachycardia and ventricular tachycardia.

<span class="mw-page-title-main">Dofetilide</span> Antiarrhythmic medication

Dofetilide is a class III antiarrhythmic agent. It is marketed under the trade name Tikosyn by Pfizer, and is available in the United States in capsules containing 125, 250, and 500 µg of dofetilide. It is not available in Europe or Australia.

<span class="mw-page-title-main">Torsades de pointes</span> Type of abnormal heart rhythm

Torsades de pointes, torsade de pointes or torsades des pointes (TdP) is a specific type of abnormal heart rhythm that can lead to sudden cardiac death. It is a polymorphic ventricular tachycardia that exhibits distinct characteristics on the electrocardiogram (ECG). It was described by French physician François Dessertenne in 1966. Prolongation of the QT interval can increase a person's risk of developing this abnormal heart rhythm, occurring in between 1% and 10% of patients who receive QT-prolonging antiarrhythmic drugs.

<span class="mw-page-title-main">Flecainide</span> Antiarrhythmic medication used to prevent and treat tachyarrhythmias

Flecainide is a medication used to prevent and treat abnormally fast heart rates. This includes ventricular and supraventricular tachycardias. Its use is only recommended in those with dangerous arrhythmias or when significant symptoms cannot be managed with other treatments. Its use does not decrease a person's risk of death. It is taken by mouth or injection into a vein.

<span class="mw-page-title-main">QT interval</span> Measurement made on an electrocardiogram

The QT interval is a measurement made on an electrocardiogram used to assess some of the electrical properties of the heart. It is calculated as the time from the start of the Q wave to the end of the T wave, and approximates to the time taken from when the cardiac ventricles start to contract to when they finish relaxing. An abnormally long or abnormally short QT interval is associated with an increased risk of developing abnormal heart rhythms and sudden cardiac death. Abnormalities in the QT interval can be caused by genetic conditions such as long QT syndrome, by certain medications such as sotalol or pitolisant, by disturbances in the concentrations of certain salts within the blood such as hypokalaemia, or by hormonal imbalances such as hypothyroidism.

<span class="mw-page-title-main">Fluconazole</span> Antifungal medication

Fluconazole is an antifungal medication used for a number of fungal infections. This includes candidiasis, blastomycosis, coccidioidomycosis, cryptococcosis, histoplasmosis, dermatophytosis, and tinea versicolor. It is also used to prevent candidiasis in those who are at high risk such as following organ transplantation, low birth weight babies, and those with low blood neutrophil counts. It is given either by mouth or by injection into a vein.

<span class="mw-page-title-main">Sotalol</span> Medication

Sotalol, sold under the brand name Betapace among others, is a medication used to treat and prevent abnormal heart rhythms. Evidence does not support a decreased risk of death with long term use. It is taken by mouth or given by injection into a vein.

<span class="mw-page-title-main">Romano–Ward syndrome</span> Medical condition

Romano–Ward syndrome is the most common form of congenital Long QT syndrome (LQTS), a genetic heart condition that affects the electrical properties of heart muscle cells. Those affected are at risk of abnormal heart rhythms which can lead to fainting, seizures, or sudden death. Romano–Ward syndrome can be distinguished clinically from other forms of inherited LQTS as it affects only the electrical properties of the heart, while other forms of LQTS can also affect other parts of the body.

hERG Mammalian protein found in humans

hERG is a gene that codes for a protein known as Kv11.1, the alpha subunit of a potassium ion channel. This ion channel is best known for its contribution to the electrical activity of the heart: the hERG channel mediates the repolarizing IKr current in the cardiac action potential, which helps coordinate the heart's beating.

<span class="mw-page-title-main">Azimilide</span> Chemical compound

Azimilide is a class ΙΙΙ antiarrhythmic drug. The agents from this heterogeneous group have an effect on the repolarization, they prolong the duration of the action potential and the refractory period. Also they slow down the spontaneous discharge frequency of automatic pacemakers by depressing the slope of diastolic depolarization. They shift the threshold towards zero or hyperpolarize the membrane potential. Although each agent has its own properties and will have thus a different function.

<span class="mw-page-title-main">Droperidol</span> Antidopaminergic drug

Droperidol is an antidopaminergic drug used as an antiemetic and as an antipsychotic. Droperidol is also often used as a rapid sedative in intensive-care treatment, and where "agitation aggression or violent behavior" are present.

<span class="mw-page-title-main">Dronedarone</span> Drug

Dronedarone, sold under the brand name Multaq, is a medication by Sanofi-Aventis, mainly for the indication of cardiac arrhythmias. It was approved by the FDA on July 2, 2009. It was recommended as an alternative to amiodarone for the treatment of atrial fibrillation and atrial flutter in people whose hearts have either returned to normal rhythm or who undergo drug therapy or electric shock treatment i.e. direct current cardioversion (DCCV) to maintain normal rhythm. It is a class III antiarrhythmic drug. In the United States, the FDA approved label includes a claim for reducing hospitalization, but not for reducing mortality, as a reduction in mortality was not demonstrated in the clinical development program. A trial of the drug in heart failure was stopped as an interim analysis showed a possible increase in heart failure deaths, in patients with moderate to severe CHF.

<span class="mw-page-title-main">Ranolazine</span> Drug used to treat angina

Ranolazine, sold under the brand name Ranexa among others, is a medication used to treat heart related chest pain. Typically it is used together with other medications when those are insufficient. Benefits appear smaller in women than men. It is taken by mouth.

Raymond L. Woosley is an American pharmacologist who is the founding president and chairman of the board for AZCERT, a not-for-profit organization dedicated to improved outcomes from the use of medications. Prior to leading AZCERT, he was founder and President of Critical Path Institute (C-Path). C-Path is an independent, non-profit organization created by the U.S. Food and Drug Administration (FDA) and the University of Arizona to help launch the critical path initiative. Previously, he has served as Vice-President for Health Sciences and Dean of the College of Medicine at the University of Arizona. He is Professor of Medicine and Biomedical Informatics in the University of Arizona College of Medicine - Phoenix, Arizona.

<span class="mw-page-title-main">AZD1305</span> Chemical compound

AZD1305 is an experimental drug candidate that is under investigation for the management and reversal of cardiac arrhythmias, specifically atrial fibrillation and flutter. In vitro studies have shown that this combined-ion channel blocker inhibits rapidly the activating delayed-rectifier potassium current (IKr), L-type calcium current, and inward sodium current (INa).

QT prolongation is a measure of delayed ventricular repolarisation, which means the heart muscle takes longer than normal to recharge between beats. It is an electrical disturbance which can be seen on an electrocardiogram (ECG). Excessive QT prolongation can trigger tachycardias such as torsades de pointes (TdP). QT prolongation is an established side effect of antiarrhythmics, but can also be caused by a wide range of non-cardiac medicines, including antibiotics, antidepressants, antihistamines, opioids, and complementary medicines. On an ECG, the QT interval represents the summation of action potentials in cardiac muscle cells, which can be caused by an increase in inward current through sodium or calcium channels, or a decrease in outward current through potassium channels. By binding to and inhibiting the “rapid” delayed rectifier potassium current protein, certain drugs are able to decrease the outward flow of potassium ions and extend the length of phase 3 myocardial repolarization, resulting in QT prolongation.

<span class="mw-page-title-main">Pharmacological cardiotoxicity</span>

Pharmacological cardiotoxicity is a cardiac damage under the action of drugs and it can occur both affecting the performances of the cardiac muscle and by altering the ion channels/currents of the functional cardiac cells, named the cardiomyocytes.

References

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  2. Schepker K. “CredibleMeds” – New Private-Public Project Aims to Reduce Antibiotic Side-Effects. Holistic Primary Care-News for Health & Healing. Published 19 October 2016. https://holisticprimarycare.net/topics/topics-h-n/holistech/1837-crediblemeds-new-private-public-collaboration-aims-to-reduce-inappropriate-antibiotic-use.html (accessed 18 June 2019).
  3. Poluzzi E, Raschi E, Diemberger I, De Ponti F. Drug-Induced Arrhythmia: Bridging the Gap Between Pathophysiological Knowledge and Clinical Practice. Drug Safety. 2017;40:461-4.
  4. CredibleMeds. The Journal of QT informatics. http://qtinformatics.com/crediblemeds/ Archived 2019-06-16 at the Wayback Machine (accessed 18 June 2019).
  5. CredibleMeds Filtered QTDrug List. Continuing Pharmacy Professional Development. The University of British Columbia Faculty of Pharmaceutical Sciences. https://cpd.pharmacy.ubc.ca/sites/cpd.pharmacy.ubc.ca/files/uploads/Update_2016/DLi_WS4_Drug_Interact/CredibleMeds%20Filtered%20QTDrug%20List%20Feb%2021%2C%202016.pdf (accessed 18 June 2019).
  6. Drugs That Prolong the QT Interval and/or Induce Torsades de Pointes. Sudden Arrhythmia Death Syndromes (SADS) Foundation. https://www.sads.org/living-with-sads/Drugs-to-Avoid#.XQZzNY97nIU (accessed 18 June 2019).
  7. Al-Khatib SM, LaPointe NM, Kramer JM, Califf, RM. What Clinicians Should Know About the QT Interval. Journal of American Medicine Association. 2003;289:2120-7.
  8. LaPointe NM, Al-Khatib SM, Kramer JM, Califf RM. Knowledge Deficits Related to the QT Interval Could Affect Patient Safety. Annals of Noninvasive Electrocardiology. 2003;8:157-60.
  9. Reidenberg MM. Centers for Education and Research in Therapeutics. Clinical Pharmacology and Therapeutics (2000) 68:109-10.
  10. QTdrugs.org
  11. Schwartz PJ, Woosley RL. Predicting the Unpredictable: Drug-Induced QT Prolongation and Torsades de Pointes. Journal of the American College of Cardiology (2016) 67.13:1639-1650.
  12. Yap YG, Camm AJ. Drug induced QT prolongation and torsades de pointes. Heart. 2003;89(11):1363–1372. doi:10.1136/heart.89.11.1363
  13. Miranda DG, McMain CL, Smith AJ. Medication-induced QT-interval prolongation and torsades de pointes. US Pharm. 2011;36(2):HS-2-HS-8.
  14. Krantz MJ, Martin J, Stimmel B, Mehta D, Haigney MC. QTc interval screening in methadone treatment. Annals of Internal Medicine. 2009;150:387–395. doi: 10.7326/0003-4819-150-6-200903170-00103
  15. Medsafe. Drug-induced QT prolongation and torsades de pointes - the facts. Prescriber Update 2010;31(4): 27-29. https://www.medsafe.govt.nz/profs/PUArticles/PDF/Prescriber%20Update%20Dec%202010.pdf (accessed 18 June 2019).