Skip to Main Content
The first stop for professional medicines advice

Managing medicines associated with QT interval prolongation

Last updated See all updates
Topics: Adverse effectsCardiovascular system disordersInteractions

Guidance on patient assessment and management of medicines associated QT interval prolongation.

Contents

  1. Safety concerns
  2. Understanding QT interval
    1. Measurement
    2. QT interval prolongation
  4. Risk factors
    1. Patient risk factors
    2. Medicines risk factors
  6. Assessing and managing the risk in practice
    1. Assess patient risk factors
    2. Assess medicine risk
    3. Correct modifiable risk factors
    4. Check product licence restrictions
    5. Counsel on QT interval prolongation symptoms
    6. Monitor ECG
    7. Actions based on ECG findings
  8. Example medicines
  9. Update history

Safety concerns

The Medicines and Healthcare products Regulatory Agency (MHRA) has issued multiple safety communications highlighting the risk of QT interval prolongation with commonly used medicines.

A prolonged QT interval on an echocardiogram (ECG) increases the risk of life-threatening arrhythmias including torsade de pointes (TdP).

There is no exhaustive list of medicines prolonging QT interval.

Our step-wise approach supports the identification and management of medicines associated with QT interval prolongation.

Understanding QT interval

The QT interval represents the time from the start of ventricular depolarisation to the end of ventricular repolarisation. It reflects how long the ventricles take to activate and then recover electrically before the next beat.

Measurement

The QT interval is measured in milliseconds (ms), using an ECG.

The QT interval varies with heart rate. It is corrected and expressed as the QTc interval.

Normal ECG QTc intervals

  • Men: up to 450 ms
  • Children, adolescents and women: up to 460 ms
  • Full term neonates: up to 470 ms

QT interval prolongation

Symptoms

Many people with QT interval prolongation do not have any symptoms.

Some may present with palpitations, syncope or presyncope, angina.

Others may also present with symptoms of reduced cardiac output, such as cold and clammy extremities, fatigue, listlessness, poor effort tolerance, dizziness, and oliguria.

Any suspicion of QT interval prolongation should be confirmed with an ECG.

ECG QTc findings suggestive of QT interval prolongation

The following ECG QTc interval findings may indicate QT prolongation:

  • Indicative: an absolute increase of 20 to 60 ms from baseline
  • Men: between 450 to 500 ms
  • Children, adolescents and women: between 460 to 500 ms
  • Full term neonates: between 470 to 500 ms

High risk QTc readings

The following ECG findings are associated with an increased risk of TdP:

  • a QTc interval of more than 500 ms
  • an absolute QTc increase of greater than 60 ms from baseline

Risk factors

These can be divided into patient and medicine risk factors.

Patient risk factors

Categorised as modifiable and non-modifiable.

Most clinical cases of drug induced QT prolongation occur in the presence of at least one of these risk factors.

Non-modifiable risk factors

These could increase the risk of QT interval prolongation:

  • age over 65 years
  • congenital long QTc interval syndrome
  • family history of sudden death
  • female gender at birth
  • genetic variations affecting the medicine’s therapeutic or side effects
  • impaired liver or kidney function
  • nocturnal or undiagnosed hypoglycaemia in people with diabetes
  • structural or conduction related cardiac disease such as heart failure, myocardial infarction, recent conversion from atrial fibrillation, or ventricular hypertrophy
  • thyroid disease

Modifiable risk factors

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

  • bradycardia secondary to acute condition(s)
  • concurrent use of medicines that could induce QT interval prolongation
  • uncorrected electrolyte disturbances such as low potassium, calcium or magnesium levels

The list is non-exhaustive. A comprehensive list of risk factors is available at the credible meds website. 

Medicines risk factors

Several medicines can cause QT interval prolongation. They may act directly on cardiac ion channels, cause electrolyte disturbances, or result in pharmacodynamic interactions.

Direct effect on the heart

Medicines may exert a direct effect on cardiac ion channels, resulting in delayed cardiac repolarisation and QT interval prolongation.

The effects and associated risk are not confined to specific therapeutic classes and cannot be reliably predicted from pharmacological action alone. The degree of QT interval prolongation is also influenced by dose and systemic exposure.

The risk can be stratified according to the degree of QTc interval prolongation associated with the medicine(s).

  • low risk: less than 10 ms QTc increase from baseline
  • moderate risk: 10 to 20 ms QTc increase from baseline
  • high risk: more than 20 ms QTc increase from baseline

Electrolyte disturbances

Diuretics and chronic use of laxatives could contribute to excessive fluid and electrolytes losses, leading to hypokalaemia, hypomagnesia, and hypocalcaemia.

Pharmacodynamic interactions

Using two or more medicines which cause QT interval prolongation can have additive effects.

Several medicines can also inhibit the key metabolic enzymes involved in the breakdown of QT interval prolonging medicines. This increases and prolongs the QT interval prolonging effects.

For example, erythromycin and escitalopram can both prolong the QTc interval. In addition, erythromycin inhibits CYP3A4, which may increase escitalopram exposure and further increase the risk of QTc prolongation.

Assessing and managing the risk in practice

The following diagram and step-wise process advises on the assessment and management of medicine QT interval prolongation risk.

 

Flow chart of the step-wise process on the assessment and management of medicine QT interval prolongation risk. Flow chart is explained in writing underneath the image.

 

  1. Review the person’s modifiable and non-modifiable risk factors.

  2. Review whether the medicine carries a risk of causing QT interval prolongation.

    Use the following resources:

    Summary of Product Characteristics

    Where a medicine has QT interval prolongation properties, this should be listed in the manufacturer’s Summary of Product Characteristics (SmPC), available on the via electronic Medicines Compendium (EMC) and MHRA .

    The warning may be listed under contraindications (section 4.3), special warnings and precautions for use (section 4.4), interactions (section 4.5), undesirable effects (section 4.8) and pharmacodynamic properties (section 5.1).

    Also review the pharmacokinetics (section 5.2) for bioavailability information. The effect of QT interval prolongation often correlates to dose and bioavailability.

    Credible meds website

    The credible meds website is a US site that provides a free searchable database of medicines that cause a long QTc interval and induce TdP.

    Registration is required.

    British National Formulary

    The BNF and BNFc monographs provide information regarding QT interval prolongation in the contraindications, cautions, interactions or side effects sections.

    Stockley’s Drug Interactions

    Stockley’s Drug Interactions (Medicines Complete subscription required) identifies drug interactions that could lead to or have additive risks of QT interval prolongation. The resource also provides a table which outlines the degree of the QTc interval change.

  3. Address modifiable risk factors before initiating therapy, such as:

    • correcting electrolyte abnormalities
    • stopping or adjusting interacting medicines
    • treating underlying conditions contributing to QT interval prolongation

     

  4. Review the SmPC, available on the via EMC and MHRA. Decide if the QT interval prolonging medicine is contraindicated or cautioned in people with risk factors or when used with other QT interval prolonging medicines.

    If the medicine is contraindicated in combination with patient risk factors or other medicines, prescribe an alternative medicine whenever possible. If no suitable alternative exists, carry out a risk assessment, considering the medication’s bioavailability, dose and duration.

    If the risk remains high, seek specialist advice, such as a cardiology referral.

    If the medicine is cautioned but no alternative is available, document your decision clearly, and follow the next steps.

  5. Inform the person about the potential cardiac side effects of the medicine(s) and explain the symptoms that may indicate QT interval prolongation.

    Advise the person to seek medical attention promptly if these symptoms occur.

  6. Some manufacturers provide specific ECG monitoring recommendations in the SmPC.

    Specialist services that routinely prescribe QT interval prolonging medicines may also provide local monitoring guidelines.

    Follow these recommendations where available.

    In the absence of specific guidance, you will have to determine the need for ECG monitoring on a case-by-case basis, taking into account:

    • patient non-modifiable risk factors
    • medicine risks such as medicine dose and duration, degree of QTc prolongation
    • whether concurrent QT interval prolonging medicine is being prescribed

     

    The following approach based on QT interval prolongation risk may be used as a guide:

    Low risk medicines and no patient risk factors

    No ECG monitoring is required.

    Medicines with a risk and non-modifiable patient risk factors

    Take a baseline ECG and repeat when the new medicine reaches steady state. For most drugs, the time to reach steady-state is four to five half-lives. Half-lives data could be found in the SmPC.

    Using 2 medicines with a risk

    Take a baseline ECG and repeat when the new medicine reaches steady state.

    Long term use of medicines with a risk

    Repeat ECG when there is an increase in dosage in long term treatment.

    Symptoms suggestive of a risk

    Perform an ECG.

  7. Take the following suggested actions based on the ECG reading:

    Normal ECG

    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 QT interval prolongation long term.

    QTc increase of 20 to 60 ms from baseline

    Consider reducing the dose or switching to an alternative medicine.

    QTc above 450 ms (men) or 470 ms (women) but below 500 ms

    Consider reducing the dose or switching to an alternative medicine.

    QTc increase of more than 60 ms from baseline

    Stop the medicine associated with QT interval prolongation.

    Review and correct any other modifiable factors affecting the QTc interval.

    Arrange urgent referral to a cardiologist.

    QTc of 500 ms or above

    Stop the medicine associated with QT interval prolongation.

    Review and correct any other modifiable factors affecting the QTc interval.

    Arrange urgent referral to a cardiologist.

Example medicines

The following article discusses how to manage risks associated with medicines known to prolong the QT interval.

Commonly used medicines associated with QT interval prolongation

Examples of medicines known to prolong the QT interval. Medicines are grouped by therapeutic class and is not a exhaustive list.

Update history

  1. Republished
  2. Article expanded to include QT limits, a stepwise approach to patient and medicine risk assessment, and guidance on monitoring and risk management. A list of example medicines is provided in a separate article.
  1. Published