I’m extremely grateful for the many pharmacists who have stepped up and provided education on topics they are passionate about. I’ve touched on QT prolongation in the past, but Daniel Lieu, PharmD has taken it up a notch! He has provided some spot-on education below on QT Prolongation for Community Pharmacists that can be applied to virtually any clinical practice. Thanks Daniel for sharing this valuable resource!
Main points – QT Prolongation for Community Pharmacists
– Although QT prolongation can precipitate torsades and sudden cardiac death, it is fortunately very rare.
– When it does occur, it’s often due to two factors: high-risk patient receiving high-risk medications.
Implications
– Don’t contribute to alert fatigue by escalating low-risk situations to the provider. (Ex. Z-pack + short-course Zofran prn, 22-yo w/o risk factors)
– Instead, look for the “needle in the haystack.” (Ex. Clarithromycin in an 85-yo female on sotalol w/ heart failure, CKD, low K and Mg)
– Given the limitations inherent to most community pharmacies – namely lack of access to a medical chart – community pharmacists must get creative, especially when assessing a patient’s risk factors. At minimum, use this guide to efficiently direct your conversations with providers.
| High-Risk Patient | Details | Tips & Tricks |
| Advanced age | Over 65 yo | Easy to assess via basic profile, even without medical chart access |
| Female | 71% of torsades cases occur in females | |
| History of certain cardiac conditions | Bradycardia, coronary artery disease, heart failure, or congenital LQTS | Look for meds on profile which imply these conditions; may also directly ask the patient or provider |
| Electrolyte imbalances | Specifically, low K, Mg, or Ca – Can be chronic or precipitated by new diuretic use or recent vomiting | Look for K, Mg, or Ca rxs or OTCs on med profile; may also directly ask the patient or provider |
| Renal or liver dysfunction | May increase the half-life of QT-prolonging medications | Look for meds on profile which may imply renal or liver dysfunction, such as phosphate-binders (i.e. Renagel), EPO (i.e. Procrit), high-quantity lactulose, Xifaxin, etc.; may also directly ask the patient or provider |
| QTc > 500ms | 2- to 3-fold torsades risk increase when QTc > 500ms – Tough to assess in community setting w/o access to the medical chart | Ask provider if baseline EKG taken to assess QTc. Asking for providers to take baseline and follow-up EKGs may be a good way to “meet in the middle,” especially if the clinical situation dictates using a high-risk medication in a high-risk patient. Long QTc interval: > 470ms for males and > 480ms for females. |
| High-Risk Meds | Details | Tips & Tricks |
| See list of meds on “Crediblemeds.org” | In-depth resource specifically focused on QT-prolongation. Categorizes meds into one of four risk categories. | Bookmark this website on your work computer. Your work’s DUR software will often flag QT-prolonging agents, but will not stratify them by risk. Lots of resources on this website. Free registration required. Mobile app also available. |
| Dose and duration | Determines peak concentration and accumulation, which can be used as a proxy to determine risk. | Ex. Zofran 4mg BID prn, qty #5, will most likely be less risky than Zofran 8mg QID scheduled, qty #40. |
| Drug interactions | CYP-mediated interactions can increase drug concentrations of QT-prolonging medications. – “Double whammy” meds both inherently increase QT and cause DDIs to increase QT. | Biggest offenders in community settings include antifungal agents, macrolides (except azithromycin), and HIV meds interacting w/ amiodarone, disopyramide, dofetilide, or pimozide. Also antidepressants (bupropion, duloxetine, fluoxetine, paroxetine) interacting w/ flecainide, quinidine, or thioridazine. (from Tisdale) |
| Laxatives / diuretics | Low K and low Mg may increase the QT interval. | Potential cause of “electrolyte imbalances” (see “High-Risk Patient” section). |
Clinical Pearls
- Torsades – and subsequent cardiac death – often occurs quite suddenly. Therefore, consultation to watch for s/sx of torsades (palpitations, dizziness, lightheadedness, SOB, syncope) may provide little practical benefit to your patients.
- Medication specific: (from Pharmacist’s Letter)
- Citalopram limited to 20mg/day in patients >60 yo per FDA d/t risk of torsades. Lower risk with other SSRIs.
- Macrolides: azithromycin poses less torsades risk than clarithromycin or erythromycin.
- Aripiprazole, olanzapine, and lurasidone may pose relatively lower torsades risk vs other antipsychotics.
- Risperidone may pose more moderate risk vs higher-risk atypical antipsychotics.
- Quantification of risk using point-based systems also available
- MedSafety Scan (https://medsafetyscan.org) provides a decision support program
- Table 7 in the Tisdale article (see below) provides a risk score table for identifying patients at greatest risk of QT prolongation
Important points
- Since many medications outside cardiology cause QT prolongation, community pharmacists play a crucial role in seeing the big picture, parsing low from high-risk scenarios, alerting and educating non-cardiology providers only when necessary, and protecting high-risk patients.
- When calling a provider, make sure to prepare questions (based on this guide) and potential solutions, just like you would before making any other provider call. (Ex. Azithromycin + cefuroxime for pneumonia in a high-risk patient; suggest doxycycline to replace azithromycin).
- QT-prolongation a very nuanced topic, and this guide is quite cursory. For example, many drugs prolong the QT interval, but not all cause torsades. As such, spend time reading the references below, and other resources, for a fuller understanding of the topic.
This guest post has been provided by Daniel Lieu, PharmD. Version 1.1 May 2020.
The content of this guide is provided for educational and informational purposes only, and is not a substitute for advice, opinion or diagnosis of other trained medical professionals.
As I am also still learning, I am open to advice or correction ([email protected]).
References
- Tisdale JE. Drug-induced QT interval prolongation and torsades de pointes: Role of the pharmacist in risk assessment, prevention and management. Can Pharm J (Ott). 2016;149(3):139‐152. doi:10.1177/1715163516641136
- Article, Avoid QT-Prolonging Meds in High-Risk Patients, Pharmacist’s Letter, March 2017
- Continuing Education Article, Prevention and Management of Drug-Induced QT Prolongation, Pharmacist’s Letter, 2015.
Crediblemeds provides information that is related to QT prolongation and drugs. There is no cost to register.
https://www.crediblemeds.org/
Awesome advice!! Loved it! Thank you so much.
Please comment on the topical issue as regards the management of COVID-19 with high dose Chloroquine or Hydroxychloroquine especially when used in combination with Azithromycin due to the risk of prolongation of QT interval and associated sudden death.
Hi Larry,
Clinical context, medication-specific factors, and patient-specific factors help determine our handling of concurrent hydroxychloroquine + azithromycin prescriptions.
1. Clinical context
– If the practice setting is inpatient, then baseline and follow-up EKG monitoring is easy. Also, inpatient usage typically implies a sicker patient, which makes us more likely to use this combo, given the lack of other treatments available for COVID.
– If the practice setting is in the general community, then EKG monitoring becomes tougher, and we might lean more towards asking further questions before dispensing.
– What is the physician’s speciality? Infectious disease or internal medicine credentials would give us more assurance of appropriate prescribing.
2. Medication-specific factors
– Dose and duration come to mind first, as these two factors determine peak concentration and accumulation, which can be used as a proxy to determine risk.
– We want to ask the same questions as we do with all other prescriptions: Is the dose and duration within the standard of practice? Does the duration imply prophylaxis or treatment? For example, we’d feel much more comfortable dispensing a four-day course of hydroxychloroquine 200mg BID + azithromycin 500mg qday to a patient finishing a 5-day treatment course after one day of hospitalization, versus dispensing an rx written for quantity #200 of each med with directions “Take as directed.”
– Per the above chart, we’d also want to look at the patient’s medication profile, and consider the impact of other QT-prolonging medications, drug interactions, or presence of laxatives / diuretics.
3. Patient-specific factors
– Per the above chart, we’d want to look at the patient’s age, sex, hx of cardiac conditions, electrolyte imbalances, renal / liver dysfunction, and QTc. The less risk factors present, the more we’d lean towards dispensing.
In my opinion, the majority of short (i.e. five day) treatment courses of hydroxychloroquine + azithromycin for outpatient use following hospitalization should almost always be dispensed. This is due to the lack of other viable treatments for COVID, assumed EKG monitoring while hospitalized, and the short duration of therapy. However, prescriptions for longer duration of therapy, especially in patients with additional risk factors, should be timed out and discussed with the provider.
Hope this helps,
Daniel
This is very useful and extremely thorough Thank you for your time and effort!
From a functional therapy perspective, if the client has completed a 3-day course of Azithromycin (500mg p/d), how soon after completion would the client be able to resume other medications with similar possible side effects (QT-prolongation) – Or would the client have to wait for the duration of the completed half-life cycles to eliminate the antibiotic before resuming prior medication/supplementation?