FDA Final Guidance on QTc Information in Human Prescription Drug and Biological Product Labeling – What Manufacturer Need to Know

The FDA released the final “QTc Information in Human Prescription Drug and Biological Product Labeling Guidance for Industry” in December 2025. This document helps drug makers include clear QTc prolongation data in labels for non-antiarrhythmic drugs and biologics. It ensures prescribers and patients understand cardiac risks linked to QTc changes.

Scope of the Guidance

This guidance applies to:

Human prescription drug and biological products that are non-antiarrhythmic (i.e., not drugs whose primary indication is the treatment of arrhythmias) but which have systemic bioavailability

Products for which QTc-interval prolongation is relevant (either because of observed data or mechanistic risk)

Labeling changes for new approvals and updates to existing approved products.

It does not apply to antiarrhythmic drugs whose labeling already addresses QT/QTc risk in specialized ways.

What is QTc Prolongation?

Drugs can delay heart repolarization, shown as a longer QT interval on an ECG, corrected for heart rate as QTc. This delay raises the risk of torsade de pointes (TdP), a dangerous rhythm that may lead to sudden death. Patients with factors like low potassium, heart failure, or other QT-prolonging drugs face higher risks.​

The guidance builds on ICH E14 rules, which call for thorough QT (TQT) studies or alternatives like concentration-QTc modeling early in development. These tests check if a drug causes a mean QTc increase over 10 ms, a key concern threshold.

Clinical Pharmacology Section Details

Place QTc effect data under the “Cardiac Electrophysiology” heading in the Clinical Pharmacology section. Describe studied doses, exposure ranges, and any dose-response link to QTc changes. Use simple statements like: “At the maximum dose, no clinically significant QTc prolongation occurred,” if studies rule out a 10 ms mean increase.​

For positive findings, state: “The largest mean QTc increase was X ms (upper CI Y ms) at [dose].” Omit this for drugs like monoclonal antibodies that skip QTc assessments.

Drug Interactions Coverage

List QTc-related interactions in a dedicated Drug Interactions subsection. Warn against combining with other QT-prolonging drugs, advising ECG checks if unavoidable. Explain risks like bigger QTc jumps leading to TdP.​

For drugs where inhibitors boost levels and QTc effects, note: “Avoid strong CYP3A inhibitors as they raise drugozide-x exposure and QTc risks.” Always include mechanisms and management steps.

Warnings and Precautions Essentials

Include a warning if QTc prolongation links to serious events like TdP, ventricular tachycardia, or sudden death. Detail adverse reaction rates, like patients exceeding QTc >500 ms or >60 ms change from baseline. Advise baseline ECGs, electrolyte checks, and avoiding high-risk patients.​

Mitigate risks by monitoring ECGs periodically, correcting electrolytes, and adjusting doses for QTc rises. Cross-reference Dosage and Administration for specifics.

Boxed Warning Requirements

FDA recommends a Boxed Warning for causal links to cardiac death, TdP, polymorphic ventricular tachycardia, or life-threatening arrhythmias with QTc prolongation. Place it at label start with trial or post-marketing evidence; cross-reference other sections for monitoring.

Dosage and Administration Modifications

Detail QTc-based dosage changes, holds, or stops in Dosage and Administration. Specify monitoring like ECGs every few weeks, based on pharmacokinetics and patient needs. Create subsections such as “2.x Dosage Modifications for QTc Interval Prolongation.”