Regions Guidelines for Managing Medications and QTc prolongation
Background:
Prolongation of QTc interval is linked with the development of potentially lifethreatening ventricular arrhythmias such as torsades de pointes (TDP). Per European
Committee for Proprietary Medicinal Products, the following are the ranges for normal,
borderline and prolonged QTc intervals (after correction with Bazett’s formula).
QTc Prolongation (msec)
1-15 years
Men
Female
<440
< 430
<450
Borderline
440-460
430-450
450-470
Abnormal
>460
> 450
> 470
Normal
QTc is considered prolonged if the values are greater than 450 msec in males and greater
than 470 msec in females. The clinical importance of QTc interval prolongation has
prompted FDA to implement rigorous guidelines for evaluating the proarrhythmic
potential of new drugs during the approval process. Based on FDA’s Clinical Evaluation
of QT/QTc Interval Prolongation and Proarrhythmic Potential for Non-Antiarrhythmic
Drugs document, an absolute QTc > 500 msec or a relative increase in the QTc interval
of ≥ 60 msec above baseline during drug administration has been a threshold of
particular concern.
Medications with risk of prolonging the QT interval were identified and stratified
according to a risk category based on FDA-approved product labeling and supporting
literature. High risk category constitutes medications that have a known potential to
prolong QT interval or carry a black box warning for potential to prolong QT interval and
cause TDP. Medium risk medications have potential for QT prolongation in
precautions/warnings section of product labeling or have been associated with welldefined cases of TDP reported in literature. Medications classified as low risk are
associated with minimal QTc prolongation.
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Antiarrhythmics:
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Phenothiazines:
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chlorpromazine
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fluphenazine
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mesoridazine
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perphenazine
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trifluoperazine
Atypicals
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clozapine
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paliperidone
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quetiapine
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risperidone
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ziprasidone
Others:
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haloperidol
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venlafaxine
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pimozide
Psychotropics:
TCAs
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amiodarone
disopyramide
dofetilide
ibutilide
procainamide
quinidine
sotalol
Psychotropics:
SSRIs:
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High Risk Medications
Miscellaneous:
citalopram
fluoxetine
paroxetine
sertraline
amitriptyline
clomipramine
desipramine
doxepin
imipramine
nortriptyline
protriptyline
trimipramine
arsenic
cisapride
droperidol
thioridazine
pentamidine
Medium Risk Medications
Antimicrobials:
Tyrosine kinase
inhibitors:
Quinolones
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moxifloxacin
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dasatinib
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levofloxacin
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lapatinib
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ofloxacin
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nilotinib
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sunitinib
Azoles:
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voriconazole
Antimalarials:
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chloroquine
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halofantrine
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mefloquine
Miscellaneous:
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alfuzosin
flecainide
fosphenytoin
indapamide
methadone
ranolazine
tacrolimus
vardenafil
Other Antibiotics:
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clarithromycin
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erythromycin
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telithromycin
Low Risk Medications
Antimicrobials:
Antiemetics:
Azoles:
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fluconazole
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itraconazole
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ketoconazole
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Miscellaneous:
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atazanavir
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azithromycin
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ciprofloxacin
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SMX/TMP
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dolasetron
palonosetron
ondansetron
granisetron
Miscellaneous:
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mexiletine
propafenone
solifenacin
Guidelines for QTc Prolongation Medication Monitoring
A. Monotherapy with any “High-Risk” Medication
1. Chronic stable patients:
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Obtain 12 lead ECG for patients chronically being administered “High-Risk” QTc prolonging
medication if ECG is not already available within last 30 days. (see attached list for “high risk
meds)
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Monitor serum drug levels when appropriate
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Consult pharmacy to adjust medication doses based on renal/hepatic function if necessary
2.
Initiation of Intravenous “High-Risk” drugs:

Obtain 12 lead ECG prior to initiation of “high- risk” QTc prolonging medications (see attached
list)
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Patient is required to have continuous telemetry monitoring during continuous intravenous
infusion of “High-Risk” QTc prolonging medications
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Document QTc every 8 hours while patient is receiving therapy
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Monitor serum drug levels when appropriate
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Consult pharmacy to adjust medication doses based on renal/hepatic function if necessary
3.
Initiation of PO scheduled “High-Risk” drugs:
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Obtain baseline 12-lead ECG
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Continuous telemetry or remote telemetry monitoring for the first 24 hours
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Document QTc every 8 hours for first 24 hours
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Then if QTc stable, 12 lead ECG daily to assess QTc for the next 48 hours, followed by QTc
once daily q72hours (or until steady state levels achieved)
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Monitor serum drug levels when appropriate
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Consult pharmacy to adjust medication doses based on renal/hepatic function if necessary
4.
For high risk PRN drug, e.g. droperidol:
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Obtain baseline 12-lead ECG
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Continuous telemetry or remote telemetry for first 24 hours
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Monitor QTc 3 hours after each dose for first 24 hours
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If continuing drug, monitor QTc once daily for next 48 hours (or until steady state levels
achieved)
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See above #3 for further guidance as appropriate
**Administer with caution the following PO medication in patients demonstrating a creatinine clearance <50
ml/min e.g. disopyramide, dofetilide, procainamide, quinidine, sotalol, droperidol, pentamidine**
B. Concurrent therapy of 2 or more agents that can prolong QTc interval
1. For all patients, pharmacist will verbally suggest monitoring QTc interval (see part D) with
prescriber in the following circumstances:
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If 2 or more high risk meds are prescribed concurrently
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If any high risk med is prescribed concurrently with any medium risk med
2.
Pharmacist will at minimum leave a Pharmacist to Prescriber communication note under
“Comments” in Epic to suggest monitoring QTc interval (see part D) in the following
circumstances*:
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If 2 or more medium risk meds are prescribed concurrently
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If any high risk med is prescribed concurrently with any low risk med
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If any medium risk med is prescribed concurrently with any low risk med
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If 2 or more low risk meds are prescribed
*call prescriber if unsure
3.
Pharmacists are to use clinical judgment when suggesting either decreasing the dose, or to
discontinue QTc prolonging drug and suggest alternative therapeutic options, e.g. alternative nonQTc prolonging antibiotics, when QTc is > 500 msec or if there is an increase of ≥ 60 msec over
baseline. Pharmacists are to document interventions as a progress note.
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C. Clinical Factors to Consider When Handling QTc Prolongation Drug Interactions
1. Does the patient have a history of cardiovascular disease, congenital long QT syndrome or
bradycardia or arrhythmias?
2. Is the patient currently monitored on telemetry or does the patient have regular EKG readings?
3. Is the baseline QTc interval prolonged (> 500 msec) or does the patient have a history of QTc
prolongation?
4. Are the interacting medications prescribed in high doses?
5. Is the patient hypokalemic or hypomagnesemic?
6. Is this a critically ill patient?
7. Does the patient have any liver dysfunction?
**Answering yes to any of the above questions should prompt pharmacist to verbally discuss and suggest
QTc monitoring instead of leaving a communication note in Epic.
D. Monitoring of patients on multiple medications that may prolong the QTc interval:
1. Recommend MD to place patient on telemetry unit or remote telemetry with specifications
for RN to monitor and document QTc for at least 24 hours
2. At minimum check QTc at baseline, then recheck subsequent QTc interval when drug
regimen (accounting for dose changes or interacting drugs) reaches steady state levels
3. Make sure magnesium and potassium levels are adequately replaced
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References:
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2003 United Hospital, St Paul, MN QTc prolongation Guidelines
www.torsades. Org accessed 4/2009
www.cmezone.com. “Drug Interactions and Drug-Induced QT Interval
Prolongation: The Role of Pharmacists”. Accessed 1/2008
Cubeddu LX. QT Prolongation and Fatal Arrhythmias: A Review of Clinical
Implications and Effects of Drugs. American Journal of Therapeutics 2003,10:
452-457
Gowda RM, et al. Torsade de pointes: the clinical considerations. International
Journal of Cardiology 2004, 96: 1-6
Owens Jr RC, et al. Antimicrobial-Associated QT Interval Prolongation: Pointes
of Interest. Clinical Infectious Diseases 2006; 43: 1603-1611
Al-Khatib SM, et al. What Clinicians Should Know About the QT Interval. JAMA
2003, 289 (16): 2120-2127
Yap YG, et al. Drug-Induced QT Prolongation and Torsades De Pointes. Heart
2003, 89: 1363-1372
Haddad PM, et al. Antipsychotic-Related QTc Prolongation, Torsades de Pointes
and Sudden Death. Drugs 2002, 62 (11): 1649
Glassman AH, et al. Antipsychotic Drugs: Prolonged QTc Interval, Torsades de
Pointes, and Sudden Death. Am J Psychiatry 2001, 158:1774-1782
Kao LW, et al. Drug-Induced Q-T Prolongation. Med Clin N Am 2005, 89: 11251144
Ng TMH, et al. Pharmacist Monitoring of QTc Interval-Prolonging Medications in
Critically Ill Medical Patients: A Pilot Study. Annals of Pharmacotherapy 2008,
42: 475-481
Zemrak WR, et al. Association of Antipsychotic and Antidepressant Drugs with
Q-T Interval Prolongation. American Journal of Health-System Pharmacy 2008,
65(11): 1029-1038
co-reviewed by Pam Triplett, RN-Cardiac Medicine Decentralized Nurse
Educator; Helen Sullinger; Uyen Dinh, PharmD; Hollie Lawrence, PharmD
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