Drug Interaction Report

Bepridil has a major potential interaction with Abnormal Electrocardiogram.

The use of bepridil is contraindicated in patients with a history of serious ventricular arrhythmias; patients with congenital or acquired QT interval prolongation syndromes; and patients treated concomitantly with class IA or III antiarrhythmic drugs or other medications that are known to produce increases in the QT interval or cause torsade de pointes. Bepridil has class I antiarrhythmic properties and can induce new arrhythmias, including ventricular tachycardia and ventricular fibrillation. Patients with other severe arrhythmias may have increased susceptibility to the proarrhythmic effects of bepridil, but use in such patients has been limited. Bepridil can also cause torsade de pointes type ventricular tachycardia secondary to its ability to prolong the QT interval. In U.S. clinical trials, the mean prolongations of QTc and QT were 8% and 10%, respectively, but increases of 25% or more occurred in 5% of the studied population for QTc and 8.7% for QT. Although the absolute safe upper limit of QT is not known, the manufacturer recommends that the dosage be reduced in patients whose QT interval exceeds 0.52 seconds during treatment. If prolongation remains excessive, the drug should be discontinued.

Bepridil has a major potential interaction with Cardiogenic Shock.

In general, calcium channel blockers (CCBs) should not be used in patients with hypotension (systolic pressure < 90 mm Hg) or cardiogenic shock. Due to potential negative inotropic and peripheral vasodilating effects, the use of CCBs may further depress cardiac output and blood pressure, which can be detrimental in these patients. The use of verapamil and diltiazem is specifically contraindicated under these circumstances.

PAZOPanib has a moderate potential interaction with Cardiovascular Conditions and Disorders.

Patients should be carefully monitored for clinical signs or symptoms of congestive heart failure. Baseline and periodic evaluation of LVEF is recommended in patients at risk of cardiac dysfunction including previous anthracycline exposure.

Bepridil has a major potential interaction with Diarrhea.

Bepridil can cause torsade de pointes type ventricular tachycardia secondary to its ability to prolong the QT interval. In U.S. clinical trials, the mean prolongations of QTc and QT were 8% and 10%, respectively, but increases of 25% or more occurred in 5% of the studied population for QTc and 8.7% for QT. Electrolyte disturbances such as hypokalemia and hypomagnesemia may augment the prolongation effect of bepridil on the QT interval and should be corrected prior to institution of bepridil therapy. In addition, patients who experience frequent, severe, and/or prolonged diarrhea may be subject to electrolyte losses and should be followed closely and managed accordingly during therapy with bepridil.

Bepridil has a major potential interaction with Electrolyte Abnormalities.

Bepridil can cause torsade de pointes type ventricular tachycardia secondary to its ability to prolong the QT interval. In U.S. clinical trials, the mean prolongations of QTc and QT were 8% and 10%, respectively, but increases of 25% or more occurred in 5% of the studied population for QTc and 8.7% for QT. Electrolyte disturbances such as hypokalemia and hypomagnesemia may augment the prolongation effect of bepridil on the QT interval and should be corrected prior to institution of bepridil therapy. In addition, patients who experience frequent, severe, and/or prolonged diarrhea may be subject to electrolyte losses and should be followed closely and managed accordingly during therapy with bepridil.

PAZOPanib has a major potential interaction with Gastrointestinal Hemorrhage.

Pazopanib may increase the risk of bleeding. Patients who have a history of hemoptysis, cerebral hemorrhage or those who have experienced clinically significant gastrointestinal hemorrhage in the past 6 months should not use this agent.

PAZOPanib has a major potential interaction with Gastrointestinal Obstruction.

Inhibitors of vascular endothelial growth factor receptors (VEGFR) may cause gastrointestinal perforation and fistulae. Avoid use of these agents in patients with ovarian cancer who have evidence of recto-sigmoid involvement by pelvic examination or bowel involvement on CT scan or clinical symptoms of bowel obstruction. Permanently discontinue these agents in patients with gastrointestinal perforation.

PAZOPanib has a major potential interaction with Gastrointestinal Perforation.

Inhibitors of vascular endothelial growth factor receptors (VEGFR) may cause gastrointestinal perforation and fistulae. Avoid use of these agents in patients with ovarian cancer who have evidence of recto-sigmoid involvement by pelvic examination or bowel involvement on CT scan or clinical symptoms of bowel obstruction. Permanently discontinue these agents in patients with gastrointestinal perforation.

Bepridil has a major potential interaction with Heart Attack.

Bepridil has class I antiarrhythmic properties and can induce new arrhythmias, including ventricular tachycardia and ventricular fibrillation. In the National Heart, Lung, and Blood Institute's Cardiac Arrhythmia Suppression Trial involving patients with asymptomatic, non-life-threatening ventricular arrhythmias who have had myocardial infarctions for less than two years previously, an excess rate of mortality/nonfatal cardiac arrest was seen in patients treated with the class I antiarrhythmic agents, encainide and flecainide, compared with that seen in patients assigned to matched placebo-treated groups. Although the applicability of these results to other antiarrhythmic agents is uncertain, the manufacturer recommends generally avoiding the use of bepridil in the post-infarction period. There is also limited experience in the use of bepridil within three months following a myocardial infarction, since it was one of the exclusion criteria in U.S. clinical trials.

Bepridil has a major potential interaction with Heart Attack.

Bepridil may have a negative inotropic effect, particularly at high dosages. Congestive heart failure has been observed infrequently (approximately 1%) in U.S. controlled clinical trials. However, experience with the use of bepridil in the presence of significantly impaired ventricular function is limited, and there is little information on the effect of concomitant administration with digoxin. Therapy with bepridil should be administered cautiously in patients with congestive heart failure, especially if they have severe left ventricular dysfunction (e.g., ejection fraction < 30%) or if they are receiving a beta-adrenergic blocker. Likewise, bepridil should not be given to patients with acute myocardial infarction and pulmonary congestion documented by X-ray on admission, since associated heart failure may be acutely worsened. Mild symptoms of cardiac failure should be under control, if possible, prior to initiating bepridil therapy.

Bepridil has a major potential interaction with Heart Block.

The use of some calcium channel blockers (CCBs) is contraindicated in patients with severe bradyarrhythmia, sick sinus syndrome (unless a functioning pacemaker is present), or heart block greater than the first degree (unless a functioning pacemaker is present). CCBs like bepridil, diltiazem and verapamil have a negative effect on AV conduction and the SA node and may exacerbate these conditions.

Bepridil has a major potential interaction with Heart Failure.

Bepridil may have a negative inotropic effect, particularly at high dosages. Congestive heart failure has been observed infrequently (approximately 1%) in U.S. controlled clinical trials. However, experience with the use of bepridil in the presence of significantly impaired ventricular function is limited, and there is little information on the effect of concomitant administration with digoxin. Therapy with bepridil should be administered cautiously in patients with congestive heart failure, especially if they have severe left ventricular dysfunction (e.g., ejection fraction < 30%) or if they are receiving a beta-adrenergic blocker. Likewise, bepridil should not be given to patients with acute myocardial infarction and pulmonary congestion documented by X-ray on admission, since associated heart failure may be acutely worsened. Mild symptoms of cardiac failure should be under control, if possible, prior to initiating bepridil therapy.

PAZOPanib has a moderate potential interaction with Heart Failure.

Patients should be carefully monitored for clinical signs or symptoms of congestive heart failure. Baseline and periodic evaluation of LVEF is recommended in patients at risk of cardiac dysfunction including previous anthracycline exposure.

PAZOPanib has a major potential interaction with History, Radiation Therapy.

Inhibitors of vascular endothelial growth factor receptors (VEGFR) may cause gastrointestinal perforation and fistulae. Avoid use of these agents in patients with ovarian cancer who have evidence of recto-sigmoid involvement by pelvic examination or bowel involvement on CT scan or clinical symptoms of bowel obstruction. Permanently discontinue these agents in patients with gastrointestinal perforation.

PAZOPanib has a moderate potential interaction with History, Thrombotic/Thromboembolic Disorder.

Venous and arterial thromboembolic events (VTE and ATE), some fatal, have been reported with the use of inhibitors of vascular endothelial growth factor receptors (VEGFR). Caution is recommended when using these agents in patients with a reported history of VTE or ATE. These agents should be discontinued in patients with serious or life-threatening VTE or ATE, including pulmonary embolism.

Bepridil has a major potential interaction with History - Myocardial Infarction.

Bepridil has class I antiarrhythmic properties and can induce new arrhythmias, including ventricular tachycardia and ventricular fibrillation. In the National Heart, Lung, and Blood Institute's Cardiac Arrhythmia Suppression Trial involving patients with asymptomatic, non-life-threatening ventricular arrhythmias who have had myocardial infarctions for less than two years previously, an excess rate of mortality/nonfatal cardiac arrest was seen in patients treated with the class I antiarrhythmic agents, encainide and flecainide, compared with that seen in patients assigned to matched placebo-treated groups. Although the applicability of these results to other antiarrhythmic agents is uncertain, the manufacturer recommends generally avoiding the use of bepridil in the post-infarction period. There is also limited experience in the use of bepridil within three months following a myocardial infarction, since it was one of the exclusion criteria in U.S. clinical trials.

PAZOPanib has a moderate potential interaction with Hypertensive Encephalopathy.

Inhibitors of vascular endothelial growth factor receptors (VEGFR) have been associated with severe increases in blood pressure. Therapy with these agents should be administered cautiously in patients with preexisting hypertension. Blood pressure should be assessed prior to initiating treatment, regularly during treatment and after discontinuation in patients with bevacizumab -induced or -exacerbated hypertension. Temporarily suspend these agents in patients with severe hypertension that is not controlled with medical management. Discontinue these agents in patients with hypertensive crisis or hypertensive encephalopathy.

Bepridil has a major potential interaction with Hypokalemia.

Bepridil can cause torsade de pointes type ventricular tachycardia secondary to its ability to prolong the QT interval. In U.S. clinical trials, the mean prolongations of QTc and QT were 8% and 10%, respectively, but increases of 25% or more occurred in 5% of the studied population for QTc and 8.7% for QT. Electrolyte disturbances such as hypokalemia and hypomagnesemia may augment the prolongation effect of bepridil on the QT interval and should be corrected prior to institution of bepridil therapy. In addition, patients who experience frequent, severe, and/or prolonged diarrhea may be subject to electrolyte losses and should be followed closely and managed accordingly during therapy with bepridil.

Bepridil has a major potential interaction with Hypotension.

In general, calcium channel blockers (CCBs) should not be used in patients with hypotension (systolic pressure < 90 mm Hg) or cardiogenic shock. Due to potential negative inotropic and peripheral vasodilating effects, the use of CCBs may further depress cardiac output and blood pressure, which can be detrimental in these patients. The use of verapamil and diltiazem is specifically contraindicated under these circumstances.

PAZOPanib has a moderate potential interaction with Interstitial Lung Disease.

Interstitial Lung Disease (ILD)/Pneumonitis has been reported with the use of pazopanib. Monitor patients for pulmonary symptoms indicative of ILD/pneumonitis and discontinue pazopanib in patients developing ILD or pneumonitis.

Bepridil has a major potential interaction with Liver Disease.

Calcium channel blockers (CCBs) are extensively metabolized by the liver. The half-lives of CCBs may be prolonged substantially in patients with severe hepatic impairment, with the potential for significant drug accumulation. In addition, the use of some CCBs has been associated with elevations in serum transaminases, both with and without concomitant elevations in alkaline phosphatase and bilirubin. While these effects may be transient and reversible, some patients have developed cholestasis or hepatocellular injury. Therapy with CCBs should be administered cautiously and often at reduced dosages in patients with significantly impaired hepatic function. Periodic monitoring of liver function is advised.

PAZOPanib has a major potential interaction with Liver Disease.

Severe and fatal hepatotoxicity has been observed with the use of pazopanib. No dose adjustment is required in patients with mild hepatic impairment. Pazopanib dose should be reduced to 200 mg per day in patients with moderate hepatic impairment. Pazopanib is not recommended in patients with severe hepatic impairment. It is recommended to monitor serum liver tests before starting treatment with pazopanib and at weeks 3, 5, 7, and 9. Thereafter, monitor at month 3 and at month 4, and as clinically indicated; periodic monitoring should then continue monthly. The use of this agent should be interrupted in patients presenting significant hepatic dysfunction and restart therapy only if clinically necessary and according to clinical recommendations.

PAZOPanib has a moderate potential interaction with Long QT Syndrome.

Pazopanib can cause QT prolongation which may lead to an increased risk for ventricular arrhythmias, including Torsade de Pointes. This agent should be administered with caution in patients with a history of QT interval prolongation, in patients taking antiarrhythmics or other medications that may prolong QT interval. Serum electrolytes should be corrected before initiating therapy with this agent. Periodic monitoring of ECGs and electrolytes is recommended in these patients.

Bepridil has a major potential interaction with Magnesium Imbalance.

Bepridil can cause torsade de pointes type ventricular tachycardia secondary to its ability to prolong the QT interval. In U.S. clinical trials, the mean prolongations of QTc and QT were 8% and 10%, respectively, but increases of 25% or more occurred in 5% of the studied population for QTc and 8.7% for QT. Electrolyte disturbances such as hypokalemia and hypomagnesemia may augment the prolongation effect of bepridil on the QT interval and should be corrected prior to institution of bepridil therapy. In addition, patients who experience frequent, severe, and/or prolonged diarrhea may be subject to electrolyte losses and should be followed closely and managed accordingly during therapy with bepridil.

Bepridil has a major potential interaction with Neutropenia.

According to the manufacturer, there have been two cases of marked leukopenia and neutropenia reported in U.S. clinical trials of over 800 patients treated with bepridil for up to five years. Both involved diabetic and elderly patients, with one case resulting in death and the other recovering after discontinuation of the drug. In a postmarketing report, a 72-year-old man with severe angina pectoris developed fever and chills associated with an absolute neutrophil count of 35/mm3 six weeks after switching from diltiazem and nitrates to bepridil and nitrates. A bone marrow biopsy revealed profound myeloid hypoplasia. The patient recovered after discontinuation of bepridil and institution of granulocyte colony-stimulating factor and broad-spectrum antibiotics. Therapy with bepridil should be administered cautiously in patients with preexisting neutropenia or agranulocytosis. The drug should be withdrawn promptly if these conditions develop during therapy.

PAZOPanib has a moderate potential interaction with Posterior Reversible Encephalopathy Syndrome.

Posterior Reversible Encephalopathy Syndrome (PRES) has been reported with the use of inhibitors of vascular endothelial growth factor receptors (VEGFR) in clinical studies. PRES is a neurological disorder which can present with headache, seizure, lethargy, confusion, blindness and other visual and neurologic disturbances. It is recommended to discontinue these agents in patients developing PRES. The safety of restarting therapy is not known. Cation is recommended if therapy is reinitiating in patients previously experiencing PRES.

Bepridil has a major potential interaction with Post MI Syndrome.

Bepridil has class I antiarrhythmic properties and can induce new arrhythmias, including ventricular tachycardia and ventricular fibrillation. In the National Heart, Lung, and Blood Institute's Cardiac Arrhythmia Suppression Trial involving patients with asymptomatic, non-life-threatening ventricular arrhythmias who have had myocardial infarctions for less than two years previously, an excess rate of mortality/nonfatal cardiac arrest was seen in patients treated with the class I antiarrhythmic agents, encainide and flecainide, compared with that seen in patients assigned to matched placebo-treated groups. Although the applicability of these results to other antiarrhythmic agents is uncertain, the manufacturer recommends generally avoiding the use of bepridil in the post-infarction period. There is also limited experience in the use of bepridil within three months following a myocardial infarction, since it was one of the exclusion criteria in U.S. clinical trials.

PAZOPanib has a moderate potential interaction with Proteinuria.

The incidence and severity of proteinuria is increased in patients taking inhibitors of vascular endothelial growth factor receptors (VEGFR). Therapy with these agents should be administered cautiously in patients with renal dysfunction. Monitoring for proteinuria and hematuria is recommended and perform baseline and periodic urinalyses during treatment, with follow up measurement as clinically indicated. It is recommended to temporarily suspend these agents in patients with moderate to severe proteinuria and to discontinue therapy in patients with nephrotic syndrome.

PAZOPanib has a moderate potential interaction with Pulmonary Embolism.

Venous and arterial thromboembolic events (VTE and ATE), some fatal, have been reported with the use of inhibitors of vascular endothelial growth factor receptors (VEGFR). Caution is recommended when using these agents in patients with a reported history of VTE or ATE. These agents should be discontinued in patients with serious or life-threatening VTE or ATE, including pulmonary embolism.

PAZOPanib has a moderate potential interaction with Pulmonary Impairment.

Interstitial Lung Disease (ILD)/Pneumonitis has been reported with the use of pazopanib. Monitor patients for pulmonary symptoms indicative of ILD/pneumonitis and discontinue pazopanib in patients developing ILD or pneumonitis.

PAZOPanib has a moderate potential interaction with Renal Dysfunction.

The incidence and severity of proteinuria is increased in patients taking inhibitors of vascular endothelial growth factor receptors (VEGFR). Therapy with these agents should be administered cautiously in patients with renal dysfunction. Monitoring for proteinuria and hematuria is recommended and perform baseline and periodic urinalyses during treatment, with follow up measurement as clinically indicated. It is recommended to temporarily suspend these agents in patients with moderate to severe proteinuria and to discontinue therapy in patients with nephrotic syndrome.

Bepridil has a major potential interaction with Sinus Node Dysfunction.

The use of some calcium channel blockers (CCBs) is contraindicated in patients with severe bradyarrhythmia, sick sinus syndrome (unless a functioning pacemaker is present), or heart block greater than the first degree (unless a functioning pacemaker is present). CCBs like bepridil, diltiazem and verapamil have a negative effect on AV conduction and the SA node and may exacerbate these conditions.

Bepridil has a major potential interaction with Tachyarrhythmia.

The use of bepridil is contraindicated in patients with a history of serious ventricular arrhythmias; patients with congenital or acquired QT interval prolongation syndromes; and patients treated concomitantly with class IA or III antiarrhythmic drugs or other medications that are known to produce increases in the QT interval or cause torsade de pointes. Bepridil has class I antiarrhythmic properties and can induce new arrhythmias, including ventricular tachycardia and ventricular fibrillation. Patients with other severe arrhythmias may have increased susceptibility to the proarrhythmic effects of bepridil, but use in such patients has been limited. Bepridil can also cause torsade de pointes type ventricular tachycardia secondary to its ability to prolong the QT interval. In U.S. clinical trials, the mean prolongations of QTc and QT were 8% and 10%, respectively, but increases of 25% or more occurred in 5% of the studied population for QTc and 8.7% for QT. Although the absolute safe upper limit of QT is not known, the manufacturer recommends that the dosage be reduced in patients whose QT interval exceeds 0.52 seconds during treatment. If prolongation remains excessive, the drug should be discontinued.

PAZOPanib has a moderate potential interaction with Thrombotic/Thromboembolic Disorder.

Venous and arterial thromboembolic events (VTE and ATE), some fatal, have been reported with the use of inhibitors of vascular endothelial growth factor receptors (VEGFR). Caution is recommended when using these agents in patients with a reported history of VTE or ATE. These agents should be discontinued in patients with serious or life-threatening VTE or ATE, including pulmonary embolism.

PAZOPanib has a moderate potential interaction with Underactive Thyroid.

Hypothyroidism has been reported in patients taking pazopanib. Therapy with pazopanib should be administered cautiously to patients with thyroid dysfunction. Baseline laboratory measurement of thyroid function is recommended and if appropriate, treatment per standard medical practice should be given prior to initiation of therapy. Clinical monitoring of thyroid function is recommended during therapy.