Interactions between Calan and Ceritinib

The verapamil in Calan has a major potential interaction with Aortic Stenosis.

The use of some calcium channel blockers (CCBs) is contraindicated in patients with advanced aortic stenosis. CCBs whose pharmacologic effect is partially dependent on their ability to reduce afterload (e.g., diltiazem, nicardipine, nifedipine, verapamil) may be of less benefit in these patients due to a fixed impedance to flow across the aortic valve and may, in fact, worsen rather than improve myocardial oxygen balance. Rarely, heart failure has developed following the initiation of these CCBs, particularly in patients receiving concomitant beta-blocker therapy.

The verapamil in Calan 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.

Ceritinib has a moderate potential interaction with Diabetes Mellitus.

The use of ceritinib causes hyperglycemia. It is recommended to monitor fasting serum glucose prior to the start of therapy and periodically thereafter as clinically indicated. Initiate or optimize antihyperglycemic medications as clinically appropriate, and withhold therapy until hyperglycemia is adequately controlled, then resume at a reduced dose as clinically appropriate. If adequate hyperglycemic control cannot be achieved with optimal medical management, permanently discontinue treatment with ceritinib. Care should be exercised when using this agent in diabetic patients.

Ceritinib has a moderate potential interaction with Diarrhea.

Severe gastrointestinal toxicity has been reported in patients treated with ceritinib. It is recommended to monitor and manage patients using standards of care, or withhold ceritinib with resumption at a reduced dose as per clinical guidelines. Care and close monitoring is recommended in patients reporting diarrhea, vomiting, or abdominal pain.

Ceritinib has a major potential interaction with Electrolyte Abnormalities.

Ceritinib can cause dose dependent QT prolongation which may lead to an increased risk for ventricular arrhythmias, including Torsade de Pointes. When possible, avoid use of ceritinib in patients with congenital long QT syndrome. It is recommended to conduct periodic monitoring with electrocardiograms (ECGs) in patients with congestive heart failure, bradyarrhythmias, electrolyte abnormalities, or those who are taking medications that are known to prolong the QTc interval. Withhold ceritinib in patients who develop a QTc interval greater than 500 msec on at least 2 separate ECGs until the QTc interval is less than 481 msec or recovery to baseline if the QTc interval is greater than or equal to 481 msec, then resume therapy at a reduced dose as clinically indicated. Permanently discontinue ceritinib in patients who develop QTc interval prolongation in combination with Torsade de pointes or polymorphic ventricular tachycardia or signs/symptoms of serious arrhythmia. This drug should be used with caution in patients with a known history of QT prolongation or patients who are taking medications known to prolong the QT interval.

The verapamil in Calan has a moderate potential interaction with Gastrointestinal Obstruction.

The controlled-onset, extended-release formulation of verapamil (Covera-HS) contains a non-deformable material. There have been rare reports of obstructive symptoms in patients with known strictures following the ingestion of similar sustained-release products. Therapy with the controlled-onset, extended-release formulation of verapamil should be administered cautiously in patients with preexisting severe gastrointestinal narrowing or obstruction, whether pathologic or iatrogenic.

The verapamil in Calan has a major potential interaction with Heart Attack.

The use of verapamil is contraindicated in patients with severe left ventricular dysfunction (e.g., ejection fraction < 30%) or moderate to severe symptoms of cardiac failure and in patients with any degree of ventricular dysfunction if they are receiving a beta-adrenergic blocker. Likewise, verapamil 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. Verapamil has a negative inotropic effect, which in most patients is compensated by a simultaneous reduction in afterload (i.e. decreased systemic vascular resistance) without a net impairment of ventricular performance. However, congestive heart failure or pulmonary edema have developed in approximately 2% of patients treated with verapamil. Mild symptoms of cardiac failure should be under control, if possible, prior to initiating verapamil therapy.

The verapamil in Calan 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.

Ceritinib has a moderate potential interaction with Heart Block.

The use of ceritinib may cause bradycardia. It is recommended to monitor heart rate and blood pressure regularly and in cases of symptomatic bradycardia that is not life-threatening, withhold therapy until recovery and adjust the dose of ceritinib. It might be necessary to permanently discontinue ceritinib for life-threatening bradycardia if no contributing concomitant medication is identified; however, if associated with a concomitant medication known to cause bradycardia or hypotension, withhold therapy until recovery and resume therapy at a reduced dose with frequent monitoring. Care and close monitoring is recommended.

The verapamil in Calan has a major potential interaction with Heart Failure.

The use of verapamil is contraindicated in patients with severe left ventricular dysfunction (e.g., ejection fraction < 30%) or moderate to severe symptoms of cardiac failure and in patients with any degree of ventricular dysfunction if they are receiving a beta-adrenergic blocker. Likewise, verapamil 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. Verapamil has a negative inotropic effect, which in most patients is compensated by a simultaneous reduction in afterload (i.e. decreased systemic vascular resistance) without a net impairment of ventricular performance. However, congestive heart failure or pulmonary edema have developed in approximately 2% of patients treated with verapamil. Mild symptoms of cardiac failure should be under control, if possible, prior to initiating verapamil therapy.

The verapamil in Calan has a major potential interaction with Hypertrophic Cardiomyopathy.

The use of verapamil in patients with hypertrophic cardiomyopathy, or idiopathic hypertrophic subaortic stenosis, has been associated with serious side effects such as pulmonary edema, severe hypotension, sinus bradycardia, AV block, sinus arrest, and death. However, a causal relationship has not been established. Therapy with verapamil should be administered cautiously in patients with hypertrophic cardiomyopathy. Dosage reduction or drug discontinuation may be required if severe adverse effects occur.

The verapamil in Calan 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.

Ceritinib has a moderate potential interaction with Interstitial Lung Disease.

The use of certain multikinase inhibitors has been associated with pulmonary toxicity. Serious cases of interstitial lung disease (ILD), including fatal cases and interstitial pneumonitis or pulmonary fibrosis have been reported. Caution is recommended when using these agents in patients with a history of interstitial pneumonitis or pulmonary fibrosis or those patients presenting with acute onset of new or progressive unexplained pulmonary symptoms such as dyspnea, cough, and fever pending diagnostic evaluation. If ILD is confirmed, these agents should be permanently discontinued and appropriate measures should be instituted. Treatment should be immediately withheld in patients diagnosed with ILD/pneumonitis and permanently discontinued if no other potential causes of ILD/pneumonitis have been identified.

The verapamil in Calan has a major potential interaction with Ischemic Heart Disease.

Increased frequency, duration, and/or severity of angina, as well as acute myocardial infarction, have rarely developed during initiation or dosage increase of calcium channel blockers (CCBs), particularly in patients with severe obstructive coronary artery disease and those treated with immediate-release formulations. The mechanism of this effect is not established. Therapy with CCBs should be administered cautiously in patients with significant coronary artery disease.

The verapamil in Calan 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.

Ceritinib has a moderate potential interaction with Liver Disease.

Ceritinib is eliminated primarily via the liver. Patients with hepatic impairment may have increased exposure and drug-induced hepatotoxicity. Based on results of population pharmacokinetic analysis no dose adjustment is needed for patients with mild hepatic impairment. The pharmacokinetics of ceritinib has not been studied in patients with moderate to severe hepatic impairment; therefore, a recommended dose has not been determined for these patients. It is recommended to monitor liver function tests including ALT, AST, and total bilirubin once a month and as clinically indicated, with more frequent testing in patients who develop transaminase elevations. In some cases, it might be necessary to withhold ceritinib and resume therapy at a reduced dose, or permanently discontinue treatment.

Ceritinib has a major potential interaction with Long QT Syndrome.

Ceritinib can cause dose dependent QT prolongation which may lead to an increased risk for ventricular arrhythmias, including Torsade de Pointes. When possible, avoid use of ceritinib in patients with congenital long QT syndrome. It is recommended to conduct periodic monitoring with electrocardiograms (ECGs) in patients with congestive heart failure, bradyarrhythmias, electrolyte abnormalities, or those who are taking medications that are known to prolong the QTc interval. Withhold ceritinib in patients who develop a QTc interval greater than 500 msec on at least 2 separate ECGs until the QTc interval is less than 481 msec or recovery to baseline if the QTc interval is greater than or equal to 481 msec, then resume therapy at a reduced dose as clinically indicated. Permanently discontinue ceritinib in patients who develop QTc interval prolongation in combination with Torsade de pointes or polymorphic ventricular tachycardia or signs/symptoms of serious arrhythmia. This drug should be used with caution in patients with a known history of QT prolongation or patients who are taking medications known to prolong the QT interval.

The verapamil in Calan has a moderate potential interaction with Myoneural Disorder.

Verapamil has been reported to decrease neuromuscular transmission in patients with Duchenne's muscular dystrophy and to prolong recovery from the neuromuscular blocking agent, vecuronium. Therapy with verapamil should be administered cautiously in patients with attenuated neuromuscular transmission or myopathy, since these conditions may be exacerbated. A reduced dosage may be appropriate.

The verapamil in Calan has a moderate potential interaction with Myopathy.

Verapamil has been reported to decrease neuromuscular transmission in patients with Duchenne's muscular dystrophy and to prolong recovery from the neuromuscular blocking agent, vecuronium. Therapy with verapamil should be administered cautiously in patients with attenuated neuromuscular transmission or myopathy, since these conditions may be exacerbated. A reduced dosage may be appropriate.

Ceritinib has a moderate potential interaction with Pancreatitis.

Pancreatitis, including a fatal case has occurred in patients receiving ceritinib. It is recommended to monitor lipase and amylase prior to the start of therapy with ceritinib and periodically thereafter as clinically indicated. It might be necessary to withhold the dose of ceritinib based on the severity of the laboratory abnormalities and resume therapy at a reduced dose per clinical guidelines. Care is recommended when using this agent in patients at risk.

The verapamil in Calan has a major potential interaction with Preexcitation Syndrome.

The use of verapamil is contraindicated for the management of atrial flutter or fibrillation in patients with an accessory AV tract (e.g., those with Wolff-Parkinson-White or Lown-Ganong-Levine syndrome). Intravenous verapamil has been reported to cause ventricular fibrillation and cardiac arrest in such patients, the mechanism of which is related to the drug's ability to shorten the refractory period and accelerate antegrade conduction within the accessory pathway. Although these events have not been associated with chronic use of oral verapamil, a similar risk may exist.

Ceritinib has a moderate potential interaction with Pulmonary Impairment.

The use of certain multikinase inhibitors has been associated with pulmonary toxicity. Serious cases of interstitial lung disease (ILD), including fatal cases and interstitial pneumonitis or pulmonary fibrosis have been reported. Caution is recommended when using these agents in patients with a history of interstitial pneumonitis or pulmonary fibrosis or those patients presenting with acute onset of new or progressive unexplained pulmonary symptoms such as dyspnea, cough, and fever pending diagnostic evaluation. If ILD is confirmed, these agents should be permanently discontinued and appropriate measures should be instituted. Treatment should be immediately withheld in patients diagnosed with ILD/pneumonitis and permanently discontinued if no other potential causes of ILD/pneumonitis have been identified.

The verapamil in Calan has a moderate potential interaction with Renal Dysfunction.

Approximately 70% of an administered dose of verapamil is excreted as metabolites in the urine. The primary metabolite, norverapamil, has about 20% the cardiovascular activity and can reach steady-state plasma concentrations approaching those of the parent drug. Patients with impaired renal function may be at greater risk for adverse effects due to drug and metabolite accumulation. Therapy with verapamil should be administered cautiously in such patients, with appropriate monitoring for excessive pharmacologic effects (e.g., abnormal prolongation of PR interval) and the dosage adjusted accordingly as necessary.

Ceritinib has a moderate potential interaction with Renal Dysfunction.

Based on results of population pharmacokinetic analyses ceritinib exposures are similar between patients with mild to moderate renal impairment and patients with normal renal function. No dose adjustment is needed for these patients. Caution and monitoring is needed when using this agent in patients with severe renal impairment as no information is available.

The verapamil in Calan 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.

Ceritinib has a moderate potential interaction with Sinus Node Dysfunction.

The use of ceritinib may cause bradycardia. It is recommended to monitor heart rate and blood pressure regularly and in cases of symptomatic bradycardia that is not life-threatening, withhold therapy until recovery and adjust the dose of ceritinib. It might be necessary to permanently discontinue ceritinib for life-threatening bradycardia if no contributing concomitant medication is identified; however, if associated with a concomitant medication known to cause bradycardia or hypotension, withhold therapy until recovery and resume therapy at a reduced dose with frequent monitoring. Care and close monitoring is recommended.

The verapamil in Calan has a major potential interaction with Ventricular Arrhythmia.

The use of intravenous diltiazem or verapamil is contraindicated in patients with ventricular tachycardia. IV administration of a calcium channel blocker can precipitate cardiac arrest in such patients. Marked hemodynamic deterioration and ventricular fibrillation have occurred in patients with wide-complex ventricular tachycardia (QRS >= 0.12 seconds) treated with IV verapamil.

Ceritinib has a moderate potential interaction with Vomiting.

Severe gastrointestinal toxicity has been reported in patients treated with ceritinib. It is recommended to monitor and manage patients using standards of care, or withhold ceritinib with resumption at a reduced dose as per clinical guidelines. Care and close monitoring is recommended in patients reporting diarrhea, vomiting, or abdominal pain.