Safety concerns

The Medicines and Healthcare products Regulatory Agency (MHRA) have issued safety alerts warning of the risk of a long QT interval with several medicines. For example: erythromycin, citalopram and ondansetron.

MHRA recommendations include:

• stating the effect of the medicine on QT interval in the contraindications and cautions section of the Summary of Product Characteristics (SmPC)
• limiting the maximum doses of some medicines for safe use such as 100mg daily for hydroxyzine.

Impact of a long QT interval

Changes in the QT interval can have a significant impact on heart rhythm. A long QT interval can lead to torsades de pointes, a life-threatening ventricular arrhythmia, and sudden cardiac death.

The QT interval represents the heart ventricles contracting and relaxing. It varies with heart rate. Formulas are used to correct the QT interval for heart rate and the data is reported as a QTc interval.

Detection and diagnosis

An electrocardiogram (ECG) can identify changes in the QT interval. A suitably trained healthcare professional can interpret an ECG and detect any problems with the heart rate or rhythm.

A normal QTc interval is considered as 450 milliseconds and a QTc interval of 500 milliseconds or longer increases the risk of torsades de pointes.

Some people with a long QT interval may experience palpitations, blackouts, or seizures; others may have no effects.

Risk factors

Risk factors which affect a QT interval can be predisposing or modifiable.

Predisposing risk factors

Take the following predisposing risk factors into account before starting a medicine known to cause a long QT interval:

• female gender
• age over 65 years
• structural or conduction related cardiac disease (e.g. heart failure, ventricular hypertrophy, myocardial infarction, recent conversion from atrial fibrillation)
• impaired liver or kidney function
• thyroid disease (more common with hypothyroidism and usually normalises with treatment)
• congenital long QT syndrome 
• family history of sudden death
• genetic variations affecting the medicine’s therapeutic or adverse effects
• diabetes

Modifiable risk factors

The following modifiable risk factors can increase the risk of a long QT interval:

• electrolyte disturbances (low potassium, calcium or magnesium levels)
• bradycardia
• medicine factors

Correct electrolyte disturbance or bradycardia prior to starting a medicine with risk of long QT interval.

Medicine risk factors

Several medicines can increase the risk of a long QT interval. Examples of medicines which can cause a long QT interval are amiodarone, citalopram, clarithromycin, and fluconazole. This list is not exhaustive.

Due to the predisposing factors impacting on risk, it is not possible to quantify the likelihood of long QT interval. The resources below will support weighing the risks from a medicine vs the benefits. Determine the action to take on a case-by-case basis taking the considerations into account.

Medicine interactions

Medicines can impact the QT interval by causing electrolyte disturbance, inhibiting the breakdown of a medicine known to cause long QT interval or by additive effects on the QT interval.

Electrolyte disturbance

Most cases of hypokalaemia are due to diuretics or loss of gastrointestinal fluids through persistent vomiting, chronic diarrhoea, or laxative abuse.

Using inhaled salbutamol is unlikely to cause low potassium levels at standard doses when given with clarithromycin. In practice this combination is usually uneventful. Correct electrolytes if necessary.

Inhibiting breakdown of medicines

Several medicines can inhibit the key enzymes involved in the breakdown of medicines. Erythromycin is an example of a medicine which inhibits CYP3A4 and can increase the QT interval directly.

Additive effect

Giving two or more medicines which cause a long QT interval can lead to additive effects. An example of this interaction is starting domperidone for nausea and vomiting in a person who takes citalopram. Avoid this combination and select an alternative medicine such as cyclizine for a short duration.

Strategies for risk minimisation

Review people on a case-by-case basis to minimise the risk of a long QT interval.

Reviewing the person

Assess the person’s predisposing and modifiable risk factors for a long QT interval:

• review and correct any modifiable risk factors
• consider carrying out a baseline ECG in people with unmodifiable risk factors
• counsel the person to report symptoms such as palpitations, light-headedness and dizziness to the GP

Initiating a new medicine

Check if the medicine can impact the QT interval:

• consider the risks and benefits of using the medicine causing a long QT interval
• review the intended duration, dose, and frequency of the medicine
• check for medicine interactions
• avoid two or more medicines which can cause a long QT interval especially if the person has unmodifiable risk factors. Prescribe an alternative medicine which does not affect the QT interval.
• carry out ECG monitoring if recommended by the manufacturer
• consider repeating the ECG once stable on the medicine known to cause long QT interval or with dose changes

Managing ECG changes

Take the following suggested actions based on the ECG reading:

• no action is required for a normal ECG. Consider repeating the ECG annually if the person has risk factors and are taking a medicine known to cause a long QT interval long term
• reduce the dose or switch to an alternative medicine if the ECG shows a QTc interval of between 450 to 500 milliseconds
• stop the medicine associated with a long QT interval if the QTc interval is more than 500 milliseconds. Review other factors affecting the QT interval. Carry out an urgent referral to a cardiologist

Useful resources

The following resources can identify medicines which can affect the QT interval:

• CredibleMeds (access is free but users must be registered) is a US site that provides a searchable database of medicines that cause a long QT interval and/or induce torsades de pointes
• British National Formulary has information in the contraindications, cautions, interactions or side effects sections of the medicine monograph
• electronic Medicines Compendium (eMC) and MHRA are sources of SmPC. They list interactions with other medicinal products and other forms of interaction in section 4.5. Other useful sections include contraindications (4.3), special warnings and precautions for use (4.4) and undesirable effects (4.8)
• Stockley’s Drug Interactions (subscription required) can identify medicine interactions and indicate medicines which can affect the QT interval

If the information is not available in the information resources listed, or if your clinical scenario is complex, you can seek further advice from our Medicines Advice service.