Special Alerts:

[Posted 10/21/2010] ISSUE: FDA notified healthcare professionals of new risk information added to the Warnings and Precautions, Contraindications, and Clinical Pharmacology sections of the antiviral drug saquinavir (Invirase), describing a potential change in the electrical activity of the heart when saquinavir is used with another antiviral medication, ritonavir (Norvir). Changes in the electrical activity of the heart may lead to abnormal heart rhythms, known as prolonged QT or PR intervals. A prolonged QT interval can lead to a serious abnormal rhythm called torsades de pointes, which can be fatal. A prolonged PR interval can lead to a serious abnormal rhythm called complete heart block. Torsades de pointes and complete heart block have been reported in patients taking saquinavir with ritonavir

BACKGROUND: The medications saquinavir and ritonavir are given together to treat HIV infection. Ritonavir must be given at a low dose with saquinavir in order to increase the level of saquinavir in the body. In February 2010, FDA announced it was reviewing clinical trial data about a potentially serious effect on the heart from the use of saquinavir in combination with ritonavir. This new information was derived from a clinical study designed to study a drug’s impact on the electrical activity of the heart.

RECOMMENDATION: Patients at particular risk are those with underlying heart conditions or those who have existing heart rate or rhythm problems. An electrocardiogram should be performed prior to initiation of treatment. Physicians consider whether ongoing EKG monitoring is appropriate for patients and when it should be done. The Data Summary in the Drug Safety Communication provides more details.

FDA will require that a Medication Guide be given to patients when picking up a prescription for Invirase. The Medication Guide will include information on the risk of abnormal heart rhythms. For more information visit the FDA website at: [Web] and [Web].

[Posted 02/23/2010] FDA notified healthcare professionals and patients that it is reviewing clinical trial data about a potentially serious effect on the heart from the use of saquinavir (Invirase) in combination with ritonavir (Norvir), antiviral medications given together to treat HIV infection.

The data suggest that together the two drugs may affect the electrical activity of the heart, known as prolonged QT or PR intervals. A prolonged QT interval can increase the risk for a serious abnormal rhythm called torsades de pointes. A prolonged PR interval can cause the electrical signal responsible for generating a heart beat to slow or even stop, known as heart block.

FDA's analysis of these data is ongoing. The agency will update the public as soon as this review is complete. However, healthcare professionals should be aware of this potential risk for changes to the electrical activity of the heart. Saquinavir and ritonavir should not be used in patients already taking medications known to cause QT interval prolongation such as Class IA (such as quinidine,) or Class III (such as amiodarone) antiarrhythmic drugs, or in patients with a history of QT interval prolongation.

Patients should not stop taking their prescribed antiviral medications. Patients who are concerned about possible risks associated with using saquinavir and ritonavir should talk to their healthcare professional.

Healthcare professionals and patients are encouraged to report adverse events or side effects related to the use of these products to the FDA's MedWatch Safety Information and Adverse Event Reporting Program:

• Online: [Web]
• Phone: 1-800-332-1088
• Mail: return the postage-paid FDA form 3500, which may be downloaded from the MedWatch “Download Forms” page ([Web]), to address on the pre-addressed form

REMS:

FDA approved a REMS for ritonavir to ensure that the benefits of a drug outweigh the risks. However, FDA later rescinded REMS requirements. See the FDA REMS page ([Web]) or the ASHP REMS Resource Center ([Web]).