Hydroxychloroquine with Azithromycin Interaction Details

Brand Names Associated with Hydroxychloroquine

Brand Names Associated with Azithromycin

Medical Content Editor Dr. Brian Staiger, PharmD
Last updated Mar 04, 2024

Interaction Effect

Increased risk of QT-interval prolongation

Interaction Summary

Hydroxychloroquine has been associated with QT interval prolongation[1], ventricular premature contractions, and torsades de pointes [2]. Hydroxychloroquine is not recommended in patients taking other drugs that have the potential to prolong the QT interval [1] or are arrhythmogenic [1][3] as life-threatening additive effects on the QT interval, including torsades de pointes, has been reported [3]

Severity

Major

Onset

Unspecified

Evidence

Probable

How To Manage Interaction

Hydroxychloroquine has been associated with QT interval prolongation[1][4][2]. There may be an increased risk of inducing ventricular arrhythmias if hydroxychloroquine is used concomitantly with other arrhythmogenic drugs. Hydroxychloroquine is not recommended in patients taking other drugs that have the potential to prolong the QT interval or are arrhythmogenic [1].

Mechanism Of Interaction

Additive QT interval effects

Literature Reports

A) In an observational study in patients who were treated with hydroxychloroquine with or without azithromycin for COVID-19, those who received both medications had significantly larger increase in QTc (+23 msec) compared with those who received hydroxychloroquine only (+5.5 msec). One patient who received both hydroxychloroquine and azithromycin developed torsades de pointes. Patients who received hydroxychloroquine alone had significantly longer baseline QTc (474 msec) compared with those who received hydroxychloroquine and azithromycin (442 msec). The majority of patients had 1 or more cardiovascular comorbidities and were taking at least 2 concomitant QTc-prolonging agents. Note that COVID-19 itself may predispose patients to risk of myocarditis or cardiomyopathy [3].

B) In a case series of patients with COVID-19, patients who received hydroxychloroquine alone had significantly lower rate of QTc increase of 500 msec or greater (5%) compared with those who received hydroxychloroquine with azithromycin (33%). Half of the patients were also receiving other agents with potential to prolong QT interval. Overall, most patients had some increase in QTc during therapy; no arrhythmias or cases of torsades de pointes were reported [5].

C) Hydroxychloroquine-associated QT interval prolongation was reported in a 41-year-old woman with congestive heart failure with systolic left ventricular dysfunction. Her comorbidities included hypertension, systemic lupus erythematosus, and stage 5 chronic kidney disease. One week after reinitiation of hydroxychloroquine therapy, a significant prolongation of the QT interval (QTc 614 msec) was observed during a routine ECG. Following treatment discontinuation of hydroxychloroquine, serial ECGs demonstrated a shortening of the QTc interval. The patient's QTc was 473 msec at a follow up 1 year after discharge [4].

D) QT prolongation and refractory ventricular arrhythmia were reported with chronic hydroxychloroquine use in a 67-year-old woman with systemic lupus erythematosus. The patient had been receiving prednisolone, theophylline, and hydroxychloroquine 200 mg/day for 1 year. The patient had a medical history of cirrhosis, hepatitis B virus related hepatoma with protal vein thrombosis, and asthma. The patient experienced a sudden episode of unconsciousness and generalized rigidity while at home. Although the patient regained consciousness within minutes and had no complaints of chest pain, palpitation, limb weakness, incontinence, or confusion, the episode recurred several times. Upon admission the ECG showed multiple ventricular premature contractions, torsades de pointes, and prolongation of the QT interval. Treatment with hydroxychloroquine was discontinued. Following medical management, ventricular arrhythmia subsided after 4 days and the QT interval shortened [2].

References

1 ) Product Information: PLAQUENIL(R) oral tablets, hydroxychloroquine sulfate oral tablets. Concordia Pharmaceuticals Inc (per FDA), Kansas City, MO, 2021.

2 ) Chen CY, Wang FL, & Lin CC: Chronic hydroxychloroquine use associated with QT prolongation and refractory ventricular arrhythmia. Clin Toxicol (Phila) 2006; 44(2):173-175.PubMed Abstract: http://www.ncbi.nlm.nih.gov/...

3 ) Mercuro NJ, Yen CF, Shim DJ, et al: Risk of QT interval prolongation associated with use of hydroxychloroquine with or without concomitant azithromycin among hospitalized patients testing positive for coronavirus disease 2019 (COVID-19). JAMA Cardiol 2020; 5(9):1036-1041.PubMed Abstract: http://www.ncbi.nlm.nih.gov/...

4 ) Morgan ND, Patel SV, & Dvorkina O: Suspected hydroxychloroquine-associated QT-interval prolongation in a patient with systemic lupus erythematosus. J Clin Rheumatol 2013; 19(5):286-288.PubMed Abstract: http://www.ncbi.nlm.nih.gov/...

5 ) Bessiere F, Roccia H, Deliniere A, et al: Assessment of QT intervals in a case series of patients with coronavirus disease 2019 (COVID-19) infection treated with hydroxychloroquine alone or in combination with azithromycin in an intensive care unit. JAMA Cardiol 2020; 5(9):1067-1069.PubMed Abstract: http://www.ncbi.nlm.nih.gov/...

Hydroxychloroquine Overview

• Hydroxychloroquine is used to prevent and treat acute attacks of malaria in adults and children weighing more than 31 kg (68 lbs). It is also used to treat discoid lupus erythematosus (DLE; a chronic inflammatory condition of the skin) or systemic lupus erythematosus (SLE or lupus; an autoimmune disease in which the immune system attacks healthy parts of the body such as joints, skin, blood vessels, and organs) and rheumatoid arthritis. Hydroxychloroquine is in a class of drugs called antimalarials and is also an antirheumatic drug. It works by killing the organisms that cause malaria. Hydroxychloroquine may work to treat rheumatoid arthritis and systemic lupus erythematosus by decreasing the activity of the immune system.

Azithromycin Overview

• Azithromycin is used to treat certain bacterial infections, such as bronchitis; pneumonia; sexually transmitted diseases (STD); and infections of the ears, lungs, sinuses, skin, throat, and reproductive organs. Azithromycin also is used to treat or prevent disseminated Mycobacterium avium complex (MAC) infection [a type of lung infection that often affects people with human immunodeficiency virus (HIV)]. Azithromycin is in a class of medications called macrolide antibiotics. It works by stopping the growth of bacteria.

• Antibiotics such as azithromycin will not work for colds, flu, or other viral infections. Using antibiotics when they are not needed increases your risk of getting an infection later that resists antibiotic treatment.

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Definitions

Severity Categories

Contraindicated

These drugs, generally, should not be used together simultaneously due to the high risk of severe adverse effects. Combining these medications can lead to dangerous health outcomes and should be strictly avoided unless otherwise instructed by your provider.

Major

This interaction could result in very serious and potentially life-threatening consequences. If you are taking this drug combination, it is very important to be under close medical supervision to minimize severe side effects and ensure your safety. It may be necessary to change a medication or dosage to prevent harm.

Moderate

This interaction has the potential to worsen your medical condition or alter the effectiveness of your treatment. It's important that you are monitored closely and you potentially may need to make adjustments in your treatment plan or drug dosage to maintain optimal health.

Minor

While this interaction is unlikely to cause significant problems, it could intensify side effects or reduce the effectiveness of one or both medications. Monitoring for changes in symptoms and your condition is recommended, and adjustments may be made if needed to manage any increased or more pronounced side effects.

Onset

Rapid: Onset of drug interaction typically occurs within 24 hours of co-administration.

Delayed: Onset of drug interaction typically occurs more than 24 hours after co-administration.

Evidence

Level of documentation of the interaction.

Established: The interaction is documented and substantiated in peer-reviewed medical literature.

Theoretical: This interaction is not fully supported by current medical evidence or well-documented sources, but it is based on known drug mechanisms, drug effects, and other relevant information.

How To Manage The Interaction

Provides a detailed discussion on how patients and clinicians can approach the identified drug interaction as well as offers guidance on what to expect and strategies to potentially mitigate the effects of the interaction. This may include recommendations on adjusting medication dosages, altering the timing of drug administration, or closely monitoring for specific symptoms.

It's important to note that all medical situations are unique, and management approaches should be tailored to individual circumstances. Patients should always consult their healthcare provider for personalized advice and guidance on managing drug interactions effectively.

Mechanism Of Interaction

The theorized or clinically determined reason (i.e., mechanism) why the drug-drug interaction occurs.

Disclaimer: The information provided on this page is for informational purposes only and should not be considered medical advice. Always consult with a qualified healthcare professional regarding your specific circumstances and medical conditions.

Where Does Our Information Come From?

Information for our drug interactions is compiled from several drug compendia, including:

• Gold Standard Drug Database
• Micromedex
• Lexicomp
• DrugBank

The prescribing information for each drug, as published on DailyMED, is also used. 

Individual drug-drug interaction detail pages contain references specific to that interaction. You can click on the reference number within brackets '[]' to see what reference was utilized.

The information posted is fact-checked by HelloPharmacist clinicians and reviewed quarterly.