FDA Drug Safety Communication: Sprycel (dasatinib) and risk of pulmonary arterial hypertension

Safety Announcement
Additional Information for Patients
Additional Information for Healthcare Professionals
Data Summary

Safety Announcement

[10-11-2011] The U.S. Food and Drug Administration (FDA) is warning the public that the leukemia drug Sprycel (dasatinib) may increase the risk of a rare, but serious condition in which there is abnormally high blood pressure in the arteries of the lungs (pulmonary arterial hypertension [PAH]). Information about this risk has been added to the Warnings and Precautions section of the Sprycel drug label.

Facts about Sprycel (dasatinib)

Used to treat certain adult patients with Philadelphia chromosome-positive chronic myeloid leukemia (CML) or acute lymphoblastic leukemia (ALL).
Works by blocking the action of an abnormal protein that signals cancer cells to multiply.¹
The cumulative worldwide exposure to Sprycel is estimated to be 32,882 patients, based on the total sales volume between initial approval in June 2006 and June 2011

As a result of PAH, the heart must work harder to pump the blood into the lungs. Over time, the overworked heart muscle may become weak and lose its ability to pump enough blood through the lungs. Symptoms of PAH may include shortness of breath, fatigue, and swelling of the body (such as the ankles and legs).

In reported cases, patients developed PAH after starting Sprycel, including after more than one year of treatment (see Data Summary below). Patients with PAH during Sprycel treatment were often taking other medications at the same time or had other co-existing medical conditions. Other medical conditions may also cause symptoms similar to those seen with PAH. Therefore, in symptomatic patients, if other causes have been ruled out, a diagnosis of Sprycel-associated PAH should be considered. PAH may be reversible if Sprycel is discontinued.

Healthcare professionals should evaluate patients for signs and symptoms of underlying cardiopulmonary disease prior to starting Sprycel and also during treatment. If PAH is confirmed, Sprycel should be permanently discontinued (see Additional Information for Healthcare Professionals below).

Patients who develop symptoms of PAH while taking Sprycel should notify their healthcare professional right away.

Additional Information for Patients

Sprycel may increase the risk of developing a rare, but serious condition in which there is abnormally high blood pressure in the arteries of the lungs. This condition is called pulmonary arterial hypertension (PAH).
Symptoms of PAH include shortness of breath, fatigue, and swelling of the body (such as the ankles and legs). Patients who develop these symptoms should notify their healthcare professional right away.
Patients should talk to their healthcare professional if they have any questions or concerns about Sprycel.
Patients should report serious side effects from the use of Sprycel to the FDA MedWatch program, using the information in the "Contact Us" box at the bottom of this page.

Additional Information for Healthcare Professionals

Sprycel may increase the risk of pulmonary arterial hypertension (PAH) which may occur anytime after initiation, including after more than one year of treatment.
Patients should be evaluated for signs and symptoms of underlying cardiopulmonary disease prior to initiating Sprycel and during treatment.
Patients with PAH during Sprycel treatment were often taking concomitant medications or had co-morbidities.
Symptoms of PAH include dyspnea, fatigue, hypoxia, and fluid retention.
Before initiating invasive procedures, more common etiologies of dyspnea associated with Sprycel therapy should be excluded, including pleural effusion, pulmonary edema, anemia, and lung infiltration.
Since PAH may be reversible upon discontinuation of Sprycel, a diagnostic approach of interruption of Sprycel treatment may be considered to observe for improvement.
Right heart catheterization can confirm the diagnosis by showing normal pulmonary capillary wedge pressure (<15 mmHg) but elevated pulmonary artery (pa) pressure (mean pa pressure>25 mmHg), indicating that the hypertension is “pre-capillary” and is not a consequence of left heart failure or chronic lung disease.
If PAH is confirmed, Sprycel should be permanently discontinued.
Healthcare professionals should report adverse events involving Sprycel to the FDA MedWatch program using the information in the "Contact Us" box at the bottom of this page.

Data Summary

Sprycel (dasatinib) was initially approved in the United States in June 2006. Since approval, cases of pulmonary arterial hypertension have been identified in the manufacturer Bristol-Myers Squibb’s global pharmacovigilance database. No fatalities from the condition have been reported.

Twelve cases of pulmonary arterial hypertension (PAH) from the manufacturer’s database were confirmed by right heart catheterization, and Sprycel was identified as the most likely cause. In these cases, symptoms were reported and PAH diagnosed after initiation of Sprycel therapy. Patients developed PAH after receiving Sprycel therapy for various time intervals, including more than one year. Patients diagnosed with PAH during Sprycel therapy were often taking concomitant medications or had co-morbidities. There may be a combination of factors contributing to the development of PAH in patients taking Sprycel. In some cases, improvements in hemodynamic and clinical parameters were observed following discontinuation of Sprycel.

References

MedlinePlus [Internet]. Bethesda (MD): National Library of Medicine (US). Drug & Supplements Monograph: Dasatinib. Available from: http://www.nlm.nih.gov/medlineplus/druginfo/meds/a607063.html. Accessed September 23, 2011.

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