Bosulif (bosutinib) Tablets
Bosulif is indicated for the treatment of adult patients with chronic phase (CP), accelerated phase (AP), and blast phase (BP) Philadelphia chromosome positive chronic myelogenous leukaemia (Ph+ CML) previously treated with one or more tyrosine kinase inhibitor(s) and for whom imatinib, nilotinib and dasatinib are not considered appropriate treatment options.
WARNINGS AND PRECAUTIONS
- An on-treatment decline in estimated glomerular filtration rate (eGFR) has occurred in patients treated with BOSULIF. Table 2 identifies the shift from baseline to lowest observed estimated glomerular filtration rate (eGFR) during BOSULIF therapy for patients in the global Ph+ Leukemia studies. The median duration of therapy with BOSULIF was approximately 17 months (range, 0.03 to 95) for patients in these studies
Source : FDA (Dec 2014)
FDA - Iclusig (ponatinib) tablets
WARNING: VASCULAR OCCLUSION, HEART FAILURE, and HEPATOTOXICITY
- Arterial and venous thrombosis and occlusions have occurred in at least 27% of Iclusig treated patients, including fatal myocardial infarction, stroke, stenosis of large arterial vessels of the brain, severe peripheral vascular disease, and the need for urgent revascularization procedures. Patients with and without cardiovascular risk factors, including patients age 50 years or younger, experienced these events
- Monitor for evidence of thromboembolism and vascular occlusion. Interrupt or stop Iclusig immediately for vascular occlusion. A benefit risk consideration should guide a decision to restart Iclusig therapy
- Arterial and venous thrombosis and occlusions, including fatal myocardial infarction, stroke, stenosis of large arterial vessels of the brain, severe peripheral vascular disease, and the need for urgent revascularization procedures have occurred in at least 27% of Iclusig-treated patients from the phase 1 and phase 2 trials. Iclusig can cause fatal and life-threatening vascular occlusion within 2 weeks of starting treatment. Iclusig can also cause recurrent or multi-site vascular occlusion …
- Fatal and serious heart failure or left ventricular dysfunction occurred in 5% of Iclusig-treated patients (N =22). Eight percent of patients (N= 35) experienced any grade of heart failure or left ventricular dysfunction. Monitor patients for signs or symptoms consistent with heart failure and treat as clinically indicated, including interruption of Iclusig. Consider discontinuation of Iclusig in patients who develop serious heart failure
- Treatment-emergent hypertension occurred in 67% of patients (300/449). Eight patients (2%) treated with Iclusig in clinical trials experienced treatment-emergent symptomatic hypertension as a serious adverse reaction, including hypertensive crisis. Patients may require urgent clinical intervention for hypertension associated with confusion, headache, chest pain, or shortness of breath
- Peripheral and cranial neuropathy have occurred in Iclusig-treated patients. Overall, 13% (59/449) of Iclusig-treated patients experienced a peripheral neuropathy event of any grade (2%, grade 3/4). In clinical trials, the most common peripheral neuropathies reported were peripheral neuropathy (4%, 18/449), paresthesia (4%, 17/449), hypoesthesia (2%, 11/449), and hyperesthesia (1%, 5/449). Cranial neuropathy developed in 1% (6/449) of Iclusig-treated patients (<1% grade 3/4).
- Serious ocular toxicities leading to blindness or blurred vision have occurred in Iclusig-treated patients. Retinal toxicities including macular edema, retinal vein occlusion, and retinal hemorrhage occurred in 3% of Iclusig-treated patients. Conjunctival or corneal irritation, dry eye, or eye pain occurred in 13% of patients. Visual blurring occurred in 6% of the patients. Other ocular toxicities include cataracts, glaucoma, iritis, iridocyclitis, and ulcerative keratitis. Conduct comprehensive eye exams at baseline and periodically during treatment
Source : FDA (Dec 2013)
FDA Drug Safety Communication: FDA investigating leukemia drug Iclusig (ponatinib) after increased reports of serious blood clots in arteries and veins
The U.S. Food and Drug Administration (FDA) is investigating an increasing frequency of reports of serious and life-threatening blood clots and severe narrowing of blood vessels (arteries and veins) of patients taking the leukemia chemotherapy drug Iclusig (ponatinib).
Health care professionals should consider for each patient, whether the benefits of Iclusig treatment are likely to exceed the risks of treatment.
Patients taking Iclusig should seek immediate medical attention if they experience symptoms suggesting a heart attack such as chest pain or pressure, pain in their arms, back, neck or jaw, or shortness of breath; or symptoms of a stroke such as numbness or weakness on one side of the body, trouble talking, severe headache, or dizziness.
Iclusig is a prescription medicine used to treat adults diagnosed with chronic phase, accelerated phase, or blast phase chronic myeloid leukemia (CML) or Philadelphia chromosome-positive (Ph+) acute lymphoblastic leukemia (ALL), who are no longer benefiting from previous treatment or who did not tolerate other treatment.
At the time of Iclusig’s approval in December 2012, the drug label contained information about the risks of blood clots in the Boxed Warning and Warnings and Precautions sections. In clinical trials conducted before approval, serious arterial blood clots occurred in 8 percent of Iclusig-treated patients, and blood clots in the veins occurred in 3 percent of Iclusig-treated patients. In the most recent clinical trial data submitted by the manufacturer to FDA, at least 20 percent of all participants treated with Iclusig have developed blood clots or narrowing of blood vessels.
Data from clinical trials and postmarket adverse event reports show that serious adverse events have occurred in patients treated with Iclusig, including heart attacks resulting in death, worsening coronary artery disease, stroke, narrowing of large arteries of the brain, severe narrowing of blood vessels in the extremities, and the need for urgent surgical procedures to restore blood flow. Other problems occurring with the drug’s use include congestive heart failure (CHF) and loss of blood flow to extremities resulting in tissue death requiring amputation. Newly identified serious adverse reactions have also been reported involving the eyes, including decreased vision and clots in blood vessels of the eye. These adverse events were seen in all age groups treated and in those with and without cardiovascular risk factors.
FDA is providing this information to patients and health care professionals while it continues its investigation. We are actively working to further evaluate these adverse events and will notify the public when more information is available.
Source : FDA (Nov 2013)
Sprycel (dasatinib) and risk of pulmonary arterial hypertension
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.
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.
- 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 mm Hg) but elevated pulmonary artery (PA) pressure (mean PA pressure >25 mm Hg), 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.
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.
Facts about Sprycel
- 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
- 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.
Source : FDA
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