Interactions between Ibrutinib and Stiripentol

Ibrutinib has a moderate potential interaction with Bleeding Associated with Coagulation Defect.

Cases of bleeding (including bruising, petechia, intracranial hemorrhage [including subdural hematoma], gastrointestinal bleeding, hematuria, and postprocedural hemorrhage), including fatal bleeding events, have been reported in patients treated with ibrutinib. Risk of major hemorrhage is increased in patients receiving antiplatelet or anticoagulant therapy; these patients should be monitored for signs/symptoms of bleeding. It is recommended to consider the benefit-risk of withholding ibrutinib for at least 3 to 7 days pre- and post-surgery depending upon the type of surgery and the risk of bleeding.

Ibrutinib has a moderate potential interaction with Bone Marrow Depression/Low Blood Counts.

Cytopenias (including neutropenia, thrombocytopenia, and anemia) have been reported with use of ibrutinib. Care should be taken with patients at risk, and complete blood counts should be monitored monthly.

Stiripentol has a moderate potential interaction with Bone Marrow Depression/Low Blood Counts.

Stiripentol can cause a significant decline in neutrophil and platelet counts. Care should be exercised when prescribing this agent to immunosuppressed patients and those with bone marrow suppression. Hematologic testing should be obtained before starting treatment, and then every 6 months.

Stiripentol has a moderate potential interaction with Central Nervous System Disorders.

Stiripentol can cause somnolence. If somnolence occurs during coadministration with clobazam, an initial reduction of clobazam by 25% should be considered. If somnolence persists, further clobazam reduction by an additional 25% should be considered, as well as adjustment of the dosage of other concomitant anticonvulsant drugs with sedating properties. Caution should be exercised when prescribing this agent to patients with CNS disorders. Prescribers should monitor patients for somnolence and should caution patients against engaging in hazardous activities requiring mental alertness (e.g., operating dangerous machinery/motor vehicles) until they know how stiripentol affects them.

Stiripentol has a moderate potential interaction with Depression.

Antiepileptic drugs (AEDs) have been associated with an increased risk of suicidal thoughts or behavior in patients taking these drugs for any indication. Pooled analyses of 199 placebo-controlled clinical studies involving the use of 11 different AEDs showed that patients receiving AEDs had approximately twice the risk of suicidal thinking or behavior compared to patients receiving placebo. AEDs should be administered cautiously in patients with depression or other psychiatric disorders; phentermine-topiramate should be avoided in patients with history of suicidal attempts or active suicidal ideation. The risk of suicidal thoughts and behavior should be carefully assessed against the risk of untreated illness, bearing in mind that epilepsy and many other conditions for which AEDs are prescribed are themselves associated with morbidity and mortality and an increased risk of suicidal thoughts and behavior. Patients, caregivers, and families should be alert to the emergence or worsening of signs and symptoms of depression, any unusual changes in mood or behavior, or the emergence of suicidal thoughts or behavior. If patients have symptoms of suicidal ideation or behavior, a dosage reduction or treatment discontinuation should be considered.

Ibrutinib has a moderate potential interaction with Diabetes Mellitus.

Fatal and serious cardiac arrhythmias and cardiac failure have occurred with ibrutinib. These adverse reactions occurred in patients with and without preexisting hypertension or cardiac comorbidities; patients with cardiac comorbidities may be at greater risk of these events. Ventricular tachyarrhythmias, atrial fibrillation, and atrial flutter have occurred in patients treated with ibrutinib, especially in patients with acute infections or cardiac risk factors (including hypertension, diabetes mellitus, history of cardiac arrhythmia). Cardiac history and function should be evaluated at baseline, and patients should be monitored for cardiac arrhythmias and cardiac function. Further evaluation (e.g., ECG, echocardiogram) should be obtained as indicated for patients who develop symptoms of arrhythmia (e.g., palpitations, lightheadedness, syncope, chest pain), new onset dyspnea, or other cardiovascular concerns. Cardiac arrhythmias and cardiac failure should be managed appropriately, dosage modification guidelines should be followed, and the risks and benefits of continued ibrutinib treatment should be considered.

Stiripentol has a moderate potential interaction with Failure to Thrive.

Stiripentol can cause decreases in appetite and weight; nausea and vomiting also occurred more often in stiripentol-treated patients. The growth of pediatric patients should be carefully monitored. In some cases, decreasing the dose of concomitant valproate by 30% per week can reduce the decrease in appetite and weight. Caution should be exercised when prescribing this agent to patients at risk.

Ibrutinib has a moderate potential interaction with Heart Disease.

Fatal and serious cardiac arrhythmias and cardiac failure have occurred with ibrutinib. These adverse reactions occurred in patients with and without preexisting hypertension or cardiac comorbidities; patients with cardiac comorbidities may be at greater risk of these events. Ventricular tachyarrhythmias, atrial fibrillation, and atrial flutter have occurred in patients treated with ibrutinib, especially in patients with acute infections or cardiac risk factors (including hypertension, diabetes mellitus, history of cardiac arrhythmia). Cardiac history and function should be evaluated at baseline, and patients should be monitored for cardiac arrhythmias and cardiac function. Further evaluation (e.g., ECG, echocardiogram) should be obtained as indicated for patients who develop symptoms of arrhythmia (e.g., palpitations, lightheadedness, syncope, chest pain), new onset dyspnea, or other cardiovascular concerns. Cardiac arrhythmias and cardiac failure should be managed appropriately, dosage modification guidelines should be followed, and the risks and benefits of continued ibrutinib treatment should be considered.

Ibrutinib has a moderate potential interaction with High Blood Pressure.

Fatal and serious cardiac arrhythmias and cardiac failure have occurred with ibrutinib. These adverse reactions occurred in patients with and without preexisting hypertension or cardiac comorbidities; patients with cardiac comorbidities may be at greater risk of these events. Ventricular tachyarrhythmias, atrial fibrillation, and atrial flutter have occurred in patients treated with ibrutinib, especially in patients with acute infections or cardiac risk factors (including hypertension, diabetes mellitus, history of cardiac arrhythmia). Cardiac history and function should be evaluated at baseline, and patients should be monitored for cardiac arrhythmias and cardiac function. Further evaluation (e.g., ECG, echocardiogram) should be obtained as indicated for patients who develop symptoms of arrhythmia (e.g., palpitations, lightheadedness, syncope, chest pain), new onset dyspnea, or other cardiovascular concerns. Cardiac arrhythmias and cardiac failure should be managed appropriately, dosage modification guidelines should be followed, and the risks and benefits of continued ibrutinib treatment should be considered.

Ibrutinib has a moderate potential interaction with High Blood Pressure.

The use of ibrutinib may cause hypertension. Blood pressure should be monitored in patients treated with this drug. Antihypertensive medication should be started or adjusted throughout ibrutinib treatment as appropriate, and the dosage modification guidelines should be followed for grade 3 or higher hypertension.

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

Cases of bleeding (including bruising, petechia, intracranial hemorrhage [including subdural hematoma], gastrointestinal bleeding, hematuria, and postprocedural hemorrhage), including fatal bleeding events, have been reported in patients treated with ibrutinib. Risk of major hemorrhage is increased in patients receiving antiplatelet or anticoagulant therapy; these patients should be monitored for signs/symptoms of bleeding. It is recommended to consider the benefit-risk of withholding ibrutinib for at least 3 to 7 days pre- and post-surgery depending upon the type of surgery and the risk of bleeding.

Stiripentol has a moderate potential interaction with Immunodeficiency.

Stiripentol can cause a significant decline in neutrophil and platelet counts. Care should be exercised when prescribing this agent to immunosuppressed patients and those with bone marrow suppression. Hematologic testing should be obtained before starting treatment, and then every 6 months.

Ibrutinib has a moderate potential interaction with Infection.

Fatal and nonfatal infections (including bacterial, viral, or fungal) have occurred with ibrutinib therapy. Cases of progressive multifocal leukoencephalopathy (PML) and Pneumocystis jirovecii pneumonia (PJP) have been reported in patients treated with ibrutinib. Prophylaxis (according to standard of care) should be considered in patients at increased risk for opportunistic infections. Patients should be monitored and evaluated for fever and infections and treated appropriately.

Ibrutinib has a moderate potential interaction with Liver Disease.

Ibrutinib is metabolized in the liver. In patients with B-cell malignancies, ibrutinib should be avoided in those with severe liver dysfunction (Child-Pugh C). The recommended dosage should be reduced when administering ibrutinib to patients with mild or moderate liver dysfunction (Child-Pugh A and B); more frequent monitoring for ibrutinib adverse reactions is recommended for these patients.

In patients with chronic graft-versus-host disease, ibrutinib should be avoided in those with total bilirubin level greater than 3 times the upper limit of normal (3 x ULN), unless of nonhepatic origin or due to Gilbert's syndrome. The recommended dosage should be reduced when administering ibrutinib to patients with total bilirubin level greater than 1.5 to 3 x ULN, unless of nonhepatic origin or due to Gilbert's syndrome.

Stiripentol has a moderate potential interaction with Liver Disease.

Stiripentol is mainly metabolized by the liver. There has been no formal study of the pharmacokinetics of stiripentol in patients with liver dysfunction. Therefore, the administration of stiripentol to patients with moderate or severe liver dysfunction is not recommended.

Stiripentol has a moderate potential interaction with Malnourishment.

Stiripentol can cause decreases in appetite and weight; nausea and vomiting also occurred more often in stiripentol-treated patients. The growth of pediatric patients should be carefully monitored. In some cases, decreasing the dose of concomitant valproate by 30% per week can reduce the decrease in appetite and weight. Caution should be exercised when prescribing this agent to patients at risk.

Stiripentol has a moderate potential interaction with Phenylketonuria.

Stiripentol for oral suspension contains phenylalanine, a component of aspartame. Phenylalanine can be harmful to patients with phenylketonuria (PKU). Before prescribing stiripentol for oral suspension to a patient with PKU, it is recommended to consider the combined daily amount of phenylalanine from all sources (including this product). Stiripentol capsules do not contain phenylalanine.

Stiripentol has a moderate potential interaction with Psychosis.

Antiepileptic drugs (AEDs) have been associated with an increased risk of suicidal thoughts or behavior in patients taking these drugs for any indication. Pooled analyses of 199 placebo-controlled clinical studies involving the use of 11 different AEDs showed that patients receiving AEDs had approximately twice the risk of suicidal thinking or behavior compared to patients receiving placebo. AEDs should be administered cautiously in patients with depression or other psychiatric disorders; phentermine-topiramate should be avoided in patients with history of suicidal attempts or active suicidal ideation. The risk of suicidal thoughts and behavior should be carefully assessed against the risk of untreated illness, bearing in mind that epilepsy and many other conditions for which AEDs are prescribed are themselves associated with morbidity and mortality and an increased risk of suicidal thoughts and behavior. Patients, caregivers, and families should be alert to the emergence or worsening of signs and symptoms of depression, any unusual changes in mood or behavior, or the emergence of suicidal thoughts or behavior. If patients have symptoms of suicidal ideation or behavior, a dosage reduction or treatment discontinuation should be considered.

Ibrutinib has a moderate potential interaction with Renal Dysfunction.

The use of ibrutinib in patients with mild to moderate renal dysfunction (CrCl greater than 25 mL/min [as estimated by Cockcroft-Gault equation]) is not expected to influence on the exposure to ibrutinib. Caution and close monitoring are recommended in patients with severe renal dysfunction and in patients on dialysis as no data are available for these patients.

Stiripentol has a moderate potential interaction with Renal Dysfunction.

Stiripentol metabolites are eliminated mainly through the kidney. There is no formal study on the pharmacokinetics and metabolism of stiripentol in patients with renal dysfunction. Therefore, the administration of stiripentol to patients with moderate or severe renal dysfunction is not recommended.

Ibrutinib has a moderate potential interaction with Smoking.

Fatal and serious cardiac arrhythmias and cardiac failure have occurred with ibrutinib. These adverse reactions occurred in patients with and without preexisting hypertension or cardiac comorbidities; patients with cardiac comorbidities may be at greater risk of these events. Ventricular tachyarrhythmias, atrial fibrillation, and atrial flutter have occurred in patients treated with ibrutinib, especially in patients with acute infections or cardiac risk factors (including hypertension, diabetes mellitus, history of cardiac arrhythmia). Cardiac history and function should be evaluated at baseline, and patients should be monitored for cardiac arrhythmias and cardiac function. Further evaluation (e.g., ECG, echocardiogram) should be obtained as indicated for patients who develop symptoms of arrhythmia (e.g., palpitations, lightheadedness, syncope, chest pain), new onset dyspnea, or other cardiovascular concerns. Cardiac arrhythmias and cardiac failure should be managed appropriately, dosage modification guidelines should be followed, and the risks and benefits of continued ibrutinib treatment should be considered.

Ibrutinib has a moderate potential interaction with Tumor Lysis Syndrome.

Tumor lysis syndrome has been reported with ibrutinib therapy infrequently. The baseline risk (e.g., high tumor burden) should be assessed and appropriate precautions should be taken. Patients should be monitored closely and treated as appropriate.