FDA Adds Cardiac Warning to HIV Drug's Label
Combination of Saquinavir, Ritonavir Can Lead to Abnormal Heart Rhythm
By News Staff
The FDA is notifying the public and health care professionals about potentially life-threatening side effects when the HIV antiviral drug saquinavir, which is marketed as Invirase, is used in combination with another antiviral agent, ritonavir, which is marketed as Norvir.
The medications are given together to treat HIV infection. Low-dose ritonavir is given to boost the level of saquinavir in the body, lowering the number of saquinavir capsules or tablets that a patient needs to take each day.
However, the FDA said in an Oct. 21 safety announcement that when used together, the two drugs could cause prolongation of the QT and/or PR intervals. Each of these changes in the heart's normal electrical activity can be detected readily on an electrocardiogram, or EKG.
According to the agency, prolongation of the QT interval can precipitate torsades de pointes, a type of ventricular tachyarrhythmia that may be self-limited or progress to ventricular fibrillation. Prolongation of the PR interval can lead to heart block of varying degree (first, second or third). Recent data from the Framingham Heart Study indicate that even first-degree heart block, once considered largely benign, increases a patient's risk of developing atrial fibrillation, of needing a pacemaker inserted or of early death.
Patients with either type of prolongation may experience lightheadedness, fainting or heart palpitations. Those who have underlying heart conditions or existing heart rate or rhythm problems are at greater risk for these cardiovascular events.
Therefore, new risk information has been added to the warnings and precautions, contraindications, and clinical pharmacology sections of saquinavir's label, and the FDA is requiring a medication guide for patients that will describe the potential risks associated with the drug.
Edward Cox, M.D., M.P.H, director of the Office of Antimicrobial Products in the FDA's Center for Drug Evaluation and Research, said in a news release that patients should inform their doctors about other medications they may be taking -- including OTC medicines, vitamins and herbal supplements -- because certain drugs may interact with saquinavir and increase the risk of developing adverse effects.
Patients with HIV infection should not stop taking their antiviral medications without talking with their health care professional.
The agency issued the following recommendations for health care professionals.
However, the FDA said in an Oct. 21 safety announcement that when used together, the two drugs could cause prolongation of the QT and/or PR intervals. Each of these changes in the heart's normal electrical activity can be detected readily on an electrocardiogram, or EKG.
According to the agency, prolongation of the QT interval can precipitate torsades de pointes, a type of ventricular tachyarrhythmia that may be self-limited or progress to ventricular fibrillation. Prolongation of the PR interval can lead to heart block of varying degree (first, second or third). Recent data from the Framingham Heart Study indicate that even first-degree heart block, once considered largely benign, increases a patient's risk of developing atrial fibrillation, of needing a pacemaker inserted or of early death.
Patients with either type of prolongation may experience lightheadedness, fainting or heart palpitations. Those who have underlying heart conditions or existing heart rate or rhythm problems are at greater risk for these cardiovascular events.
Therefore, new risk information has been added to the warnings and precautions, contraindications, and clinical pharmacology sections of saquinavir's label, and the FDA is requiring a medication guide for patients that will describe the potential risks associated with the drug.
Edward Cox, M.D., M.P.H, director of the Office of Antimicrobial Products in the FDA's Center for Drug Evaluation and Research, said in a news release that patients should inform their doctors about other medications they may be taking -- including OTC medicines, vitamins and herbal supplements -- because certain drugs may interact with saquinavir and increase the risk of developing adverse effects.
Patients with HIV infection should not stop taking their antiviral medications without talking with their health care professional.
The agency issued the following recommendations for health care professionals.
- Read the new changes in saquinavir's label carefully if you are considering or currently prescribing the medication to patients. Note that the drug is contraindicated in certain patients.
- An EKG should be performed before initiating treatment. Physicians also should consider whether ongoing electrocardiographic monitoring is appropriate for patients and when it should be done. Patients with a QT interval greater than 450 milliseconds should not receive ritonavir-boosted saquinavir. For patients with a QT interval less than 450 milliseconds, an on-treatment EKG is suggested after three to four days of therapy. Patients with a QT interval greater than 480 milliseconds or with prolongation of more than 20 milliseconds higher than the pretreatment level should discontinue combination therapy.
- A cardiology consult to confirm the EKG findings is recommended if drug discontinuation or interruption is being considered on the basis of electrocardiographic assessment.
- Patients should be advised to contact a health care professional immediately if they experience symptoms of an abnormal heart rate or rhythm while taking saquinavir and ritonavir.
- Adverse events involving the drugs should be reported to the FDA's MedWatch program.
