Section 1: Introduction -- The Silent Risk on Every ECG

A 72-year-old man in Kingston is on haloperidol 5 mg twice daily, hydrochlorothiazide 25 mg daily, and ondansetron 8 mg as needed for nausea. He has been stable on this regimen for several months. He develops a chest infection and is prescribed azithromycin 500 mg daily for five days.

On day three he collapses. The rhythm on resuscitation is torsades de pointes -- a polymorphic ventricular tachycardia that can degenerate into ventricular fibrillation and cardiac death.

Each of his drugs prolongs the QT interval to some degree. Together, they have pushed his corrected QT interval beyond the threshold at which the myocardium becomes electrically unstable. The azithromycin was the final addition to a combination that was already dangerous.

QT prolongation is invisible until it kills. There is no warning symptom, no predictable dose threshold, and no reliable way to identify which patients will develop torsades de pointes. The only intervention is to avoid the combinations that create the risk.

1.1 What the QT interval represents

The QT interval on an electrocardiogram measures the time from the beginning of ventricular depolarisation (Q wave) to the end of repolarisation (T wave). It represents the electrical recovery phase of the cardiac cycle. When this phase is prolonged, there is a window during which a premature depolarisation can trigger a potentially fatal arrhythmia.

The corrected QT interval (QTc) adjusts for heart rate. Normal QTc: below 440 ms in men, below 460 ms in women. QTc above 500 ms is associated with significantly increased arrhythmia risk.

1.2 Why this matters in the Caribbean

Four features of Caribbean clinical practice converge to make QT prolongation a specific risk:

Formulary composition. First-generation antipsychotics (haloperidol, chlorpromazine), azithromycin, domperidone, ondansetron, chloroquine, and several other QT-prolonging drugs are on Caribbean essential medicines lists and are widely prescribed.

Polypharmacy. The Caribbean patient on multiple medications for hypertension, diabetes, and cardiac disease may already carry a significant QT burden before any new QT-prolonging drug is added.

Electrolyte disturbances. Thiazide and loop diuretics -- the most widely used antihypertensives and diuretics in the Caribbean -- cause hypokalaemia and hypomagnesaemia, both of which independently prolong the QT interval and amplify the effect of QT-prolonging drugs.

Limited ECG access. Baseline QTc measurement before initiating QT-prolonging drugs requires an ECG. In many Caribbean primary care settings, ECG access is limited. QT-prolonging drugs are frequently initiated without a baseline QTc.

Section 2: Drugs That Prolong the QT Interval

2.1 The highest-risk drugs in Caribbean formularies

2.2 The additive risk -- combinations to avoid

QT prolongation is additive. Each drug that prolongs the QT interval adds to the cumulative electrical burden. The combinations below represent the highest clinical risk in Caribbean practice:

Section 3: The Patient Factors That Amplify QT Risk

Drug-induced QT prolongation does not affect all patients equally. The following patient factors increase the risk of drug-induced torsades de pointes:

3.1 Electrolyte disturbances

Hypokalaemia is the most important modifiable risk factor. Potassium is required for normal cardiac repolarisation. When serum potassium falls -- from thiazides, loop diuretics, diarrhoea, vomiting, or poor intake -- the QT interval lengthens and the threshold for arrhythmia falls.

The clinical implication is that a patient on hydrochlorothiazide or furosemide who is prescribed a QT-prolonging drug (azithromycin, haloperidol, domperidone) requires potassium checking before and during the new prescription.

Hypomagnesaemia has the same effect and is often co-present with hypokalaemia in patients on diuretics. Magnesium is required for the normal function of potassium channels in cardiac muscle.

Hypocalcaemia also prolongs the QT interval and should be checked in patients with malabsorption, vitamin D deficiency, or recent parathyroid surgery.

3.2 Female sex

Women have a naturally longer QTc than men (normal upper limit: 460 ms vs 440 ms). Women are at 2-3 times higher risk of drug-induced torsades de pointes than men. This is a pharmacogenomic difference in cardiac ion channel expression.

3.3 Bradycardia

The QT interval lengthens at slower heart rates. Bradycardia -- from beta-blockers, non-dihydropyridine CCBs (verapamil, diltiazem), hypothyroidism, or athletic training -- increases the QT-related risk from concurrent QT-prolonging drugs.

3.4 Structural heart disease

Patients with heart failure, left ventricular hypertrophy, ischaemic heart disease, or myocarditis have inherently longer QTc intervals and greater vulnerability to drug-induced arrhythmia.

3.5 Hepatic impairment

Several QT-prolonging drugs are hepatically metabolised. In hepatic impairment (Report 2), drug accumulation increases QT prolongation risk. Haloperidol, domperidone, and ondansetron are all affected by hepatic dysfunction.

3.6 Genetic predisposition -- congenital long QT syndrome

Some patients have congenital long QT syndrome (LQTS) -- a genetic condition affecting cardiac ion channels. These patients are at extreme risk from any QT-prolonging drug. LQTS may be undiagnosed. A history of unexplained syncope, near-drowning events, or a family history of sudden cardiac death in a young person should prompt consideration of LQTS before any QT-prolonging drug is prescribed.

Section 4: Domperidone -- The Caribbean-Specific Concern

Domperidone is widely used in Caribbean practice as an antiemetic and as a galactagogue (to stimulate milk production in breastfeeding women). It is available over the counter in many Caribbean pharmacies.

In 2014, the EMA issued a revised benefit-risk assessment of domperidone, concluding that it carries a small but real risk of serious cardiac arrhythmias and cardiac death, particularly at doses above 30 mg/day and in patients aged over 60. It issued updated guidance recommending:

• Limit to the lowest effective dose
• Duration: maximum one week
• Contraindicated in patients with significant hepatic impairment
• Contraindicated in patients on CYP3A4 inhibitors (which increase domperidone levels)
• Not recommended in patients over 60

In Caribbean practice, domperidone is frequently used chronically, in older patients, and alongside CYP3A4 inhibitors (clarithromycin, itraconazole, grapefruit juice) -- each of which amplifies domperidone's QT effect.

The galactagogue use is off-label in most jurisdictions. The QT risk applies even at the low doses used for this indication, particularly in patients with pre-existing risk factors.

Section 5: Azithromycin -- The Commonly Missed Interaction

Azithromycin is one of the most commonly prescribed antibiotics in the Caribbean (Report 6). Its QT-prolonging effect is moderate but its ubiquity creates clinical risk: it is added to medication lists that already contain QT-prolonging drugs without systematic interaction checking.

A 2012 study published in the New England Journal of Medicine found that azithromycin was associated with a small but statistically significant increase in cardiovascular death compared with amoxicillin, particularly in patients with the highest baseline cardiovascular risk. The absolute risk is small, but the relative risk is real.

The highest-risk combinations in Caribbean practice: - Azithromycin + haloperidol (common in psychiatric patients with infections) - Azithromycin + amiodarone (cardiac patients prescribed antibiotics for intercurrent infections) - Azithromycin + chloroquine (in malaria-endemic Caribbean territories)

The correct approach is not to avoid azithromycin in all patients on QT-prolonging drugs, but to: 1. Check whether azithromycin is necessary (most community respiratory infections do not require it -- Report 6) 2. If it is necessary, check for concurrent QT-prolonging drugs and electrolyte status 3. Consider an alternative antibiotic (doxycycline, amoxicillin) if the QT risk is high

Section 6: A Clinical Framework for QT Risk Management

Before prescribing any QT-prolonging drug:

Step 1: Check the existing medication list for other QT-prolonging drugs. Two or more QT-prolonging drugs substantially increases risk.

Step 2: Check electrolytes -- potassium and magnesium. Correct hypokalaemia and hypomagnesaemia before initiating a QT-prolonging drug where possible.

Step 3: Consider patient risk factors -- female sex, bradycardia, structural heart disease, hepatic impairment, personal or family history of syncope or sudden cardiac death.

Step 4: Obtain an ECG if risk factors are present and the drug is to be used long-term. A QTc above 500 ms is a relative contraindication to most QT-prolonging drugs.

Step 5: Use the lowest effective dose for the shortest effective duration. QT prolongation is dose-dependent for most drugs.

Step 6: Monitor. If a QT-prolonging drug is continued long-term, periodic ECG monitoring should be considered.

What to do if QTc is already prolonged:

• QTc 440-500 ms: use QT-prolonging drugs with caution; minimise combinations; correct electrolytes; monitor
• QTc above 500 ms: avoid additional QT-prolonging drugs; review existing QT-prolonging drugs for necessity; correct electrolytes; cardiology referral if unexplained

Section 7: Quick-Reference QT Interaction Table

Section 8: About ElesRx

ElesRx flags QT-prolonging drug combinations automatically. When a clinician adds a drug with QT-prolonging potential to an existing medication list, the system identifies whether other QT-prolonging drugs are already present, checks for concurrent electrolyte-depleting agents (thiazides, loop diuretics), and generates an alert with the specific risk level of the combination.

The tool is available at elesrx.com. ElesRx is a product of PIPPS Smart Apps, a division of J.C. Epiphany Limited (Jamaica, est. 1998).

Section 9: Methodology and References

9.1 Data sources

QT prolongation data is drawn from the ElesRx clinical database, the Arizona CERT drug list (CredibleMeds -- used for reference only, not reproduced), DailyMed, the European Medicines Agency, and published clinical guidelines. Drug risk classifications reflect published consensus where available.

9.2 Limitations

QT prolongation risk is probabilistic, not deterministic. The absence of QTc measurement in many Caribbean primary care settings means that risk management relies on drug and patient factor assessment rather than measured QTc. This report provides a framework for risk reduction in the absence of routine ECG access.

9.3 Author and conflict of interest disclosure

This report was authored by Juliet Duncan, BPharm, founder of J.C. Epiphany Limited and developer of ElesRx. The author has a commercial interest in ElesRx. This report is published without an access gate as a contribution to Caribbean clinical education. No external funding was received.

9.4 Citation

Duncan J. The QT Report: Drugs That Prolong the QT Interval in Caribbean Practice. ElesRx Clinical Reports, Report 13. Published 2027 at elesrx.com/reports/qt-report/. J.C. Epiphany Limited, Jamaica.

References

1. Ray WA, Murray KT, Hall K, Arbogast PG, Stein CM. Azithromycin and the risk of cardiovascular death. N Engl J Med. 2012;366(20):1881-1890. doi:10.1056/NEJMoa1003833

2. Drew BJ, Ackerman MJ, Funk M, et al. Prevention of torsade de pointes in hospital settings: a scientific statement from the American Heart Association and the American College of Cardiology Foundation. Circulation. 2010;121(8):1047-1060. doi:10.1161/CIRCULATIONAHA.109.192704

3. European Medicines Agency. Assessment report on domperidone-containing medicinal products. EMA/291276/2014. 2014.

4. Tisdale JE, Wroblewski HA, Overholser BR. Prevalence of QT interval-prolonging drug combinations and risk for ventricular arrhythmia in a cardiovascular medical unit. Am J Cardiol. 2019;124(4):583-588. doi:10.1016/j.amjcard.2019.05.027

5. CredibleMeds/AZCERT QTDrugs List. Arizona CERT. Accessed 2027. crediblemeds.org