Interactions between Stiripentol and Ziftomenib
1 drug interaction and 17 additional warnings found for the following 2 drugs:
- stiripentol
- ziftomenib
Drug interactions
Major drug interactions
Major:
stiripentol ziftomenib
Applies to: stiripentol and ziftomenib
Monitor closely
Coadministration with potent or moderate inhibitors of CYP450 3A4 may increase the plasma concentrations and effects of ziftomenib, which is primarily metabolized by the isoenzyme. Based on clinical studies, the potent CYP450 3A4 inhibitors itraconazole, voriconazole, and posaconazole are estimated to increase the systemic exposure (AUC) and peak plasma concentration (Cmax) of ziftomenib by up to 3-fold and 2-fold, respectively. The moderate CYP450 3A4 inhibitors erythromycin, fluconazole, and isavuconazole are estimated to increase the AUC and Cmax of ziftomenib by up to 2-fold. Additionally, ziftomenib is associated with concentration-dependent prolongation of the QT interval and increased levels may potentiate the risk of ventricular arrhythmias such as torsade de pointes. In general, the risk of an individual agent or a combination of agents causing ventricular arrhythmia in association with QT prolongation is largely unpredictable but may be increased by certain underlying risk factors such as congenital long QT syndrome, cardiac disease, and electrolyte disturbances (e.g., hypokalemia, hypomagnesemia, hypocalcemia).
Management
Caution is recommended if ziftomenib is used concomitantly with potent or moderate CYP450 3A4 inhibitors. If coadministration is required, patient tolerability should be assessed throughout treatment, and for those experiencing certain serious adverse effects (e.g., QT prolongation and torsade de pointes arrhythmia, differentiation syndrome, leukocytosis), ziftomenib treatment should be interrupted and/or the dose should be reduced in accordance with product labeling. Additional adverse effects to closely monitor for include diarrhea, nausea, fever, or infection. Ziftomenib should not be started if baseline QTc is greater than 480 msec. Likewise, treatment should be interrupted and adjusted in accordance with the product labeling in patients who develop QTc prolongation greater than 500 msec or have a greater than 60 msec increase in QTc from baseline. Patients should be advised to seek prompt medical attention if they experience symptoms that could indicate the occurrence of torsade de pointes such as dizziness, lightheadedness, fainting, palpitation, irregular heart rhythm, shortness of breath, or syncope. Additional consultation with individual product labeling may be advisable for further guidance.
References (1)
- (2025) "Product Information. Komzifti (ziftomenib)." Kura Oncology, Inc
Food/lifestyle interactions
Major food/lifestyle interactions
Major:
ziftomenib Food/Lifestyle
Applies to: ziftomenib
Adjust dosing interval
Food may significantly increase the oral bioavailability and plasma concentrations of ziftomenib. When ziftomenib was administered with a high-fat meal (approximately 1,000 kcal, 60% fat, 25% carbohydrate, 15% protein), the systemic exposure (AUC) and peak plasma concentration (Cmax) increased 4-fold compared with the fasted state.
Monitor closely
Grapefruit, grapefruit juice, grapefruit hybrids, pomelos, star-fruit, and Seville oranges may increase the plasma concentrations of ziftomenib. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. The extent and clinical significance are unknown. Based on clinical studies, the potent CYP450 3A4 inhibitors itraconazole, voriconazole, and posaconazole are estimated to increase the systemic exposure (AUC) and peak plasma concentration (Cmax) of ziftomenib by up to 3-fold and 2-fold, respectively. The moderate CYP450 3A4 inhibitors erythromycin, fluconazole, and isavuconazole are estimated to increase the AUC and Cmax of ziftomenib by up to 2-fold. In general, the effect of grapefruit juice is concentration-, dose- and preparation-dependent, and can vary widely among brands. Certain preparations of grapefruit juice (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition. Moreover, pharmacokinetic alterations associated with interactions involving grapefruit juice are often subject to a high degree of interpatient variability. Increased exposure to ziftomenib may increase the risk and severity of serious adverse effects, including QT interval prolongation, which has been associated with ventricular arrhythmias including torsade de pointes and sudden death.
Management
Due to the impact of high fat content meals on ziftomenib absorption and exposure, it is recommended that ziftomenib be administered on an empty stomach, at least 1 hour before or 2 hours after a meal. In addition, if grapefruit, grapefruit juice, grapefruit hybrids, pomelos, star-fruit, or Seville oranges are consumed during treatment with ziftomenib, assess patient tolerability and monitor for serious adverse effects (e.g., QT prolongation and torsade de pointes arrhythmia, differentiation syndrome, leukocytosis, infection).
References (1)
- (2025) "Product Information. Komzifti (ziftomenib)." Kura Oncology, Inc
Moderate food/lifestyle interactions
Moderate:
stiripentol Food/Lifestyle
Applies to: stiripentol
Generally avoid
Taking stiripentol on an empty stomach may reduce its oral bioavailability. Stiripentol degrades rapidly when exposed to gastric acid in an empty stomach.
Generally avoid
Alcohol may potentiate the depressant effects of stiripentol on the central nervous system. Concomitant use may result in increased sedation and dizziness as well as impairment of psychomotor skills.
Generally avoid
It is not known whether stiripentol may reduce theophylline and caffeine metabolism, as data on the potential for inhibition of CYP450 1A2 are limited. Consumption of foods and nutritional products such as cola drinks (which contain significant quantities of caffeine) and chocolate (which contains caffeine and trace amounts of theophylline) may be unsafe during treatment with stiripentol, particularly in children.
Management
Stiripentol should be taken during a meal for optimal absorption; however, it should not be taken with milk, dairy products (e.g., yogurt, soft cream cheese), fruit juice, or carbonated beverages. Patients should be advised to avoid or limit consumption of alcohol and to avoid activities requiring mental alertness such as driving or operating hazardous machinery until they know how the medication affects them. Food and beverages that may contain caffeine or theophylline such as colas, chocolate, coffee, tea, or energy drinks should also be avoided during treatment with stiripentol.
References (3)
- Canadian Pharmacists Association (2006) e-CPS. http://www.pharmacists.ca/function/Subscriptions/ecps.cfm?link=eCPS_quikLink
- EMEA. European Medicines Agency (2007) EPARs. European Union Public Assessment Reports. http://www.ema.europa.eu/ema/index.jsp?curl=pages/includes/medicines/medicines_landingpage.jsp&mid
- (2018) "Product Information. Diacomit (stiripentol)." Biocodex USA
Disease interactions
15 potential interactions Applies to: 13 conditions, including Depression, Heart Failure, Psychosis, Liver Disease, and Long QT Syndrome.
Bone Marrow Depression/Low Blood Counts
Moderate:
stiripentol
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.
Central Nervous System Disorders
Moderate:
stiripentol
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.
Depression
Moderate:
stiripentol
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.
Electrolyte Abnormalities
Moderate:
ziftomenib
Ziftomenib has a moderate potential interaction with Electrolyte Abnormalities.
Ziftomenib can cause QT (QTc) interval prolongation. Patients with congenital long QTc syndrome, congestive heart failure, electrolyte abnormalities, or who are taking medications known to prolong the QTc interval may require more frequent ECG monitoring. Perform an ECG and correct electrolyte abnormalities prior to starting treatment; do not initiate if QTcF is greater than 480 msec. Monitor ECG at least once weekly for the first 4 weeks of therapy, and at least monthly thereafter.
Failure to Thrive
Moderate:
stiripentol
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.
Heart Failure
Moderate:
ziftomenib
Ziftomenib has a moderate potential interaction with Heart Failure.
Ziftomenib can cause QT (QTc) interval prolongation. Patients with congenital long QTc syndrome, congestive heart failure, electrolyte abnormalities, or who are taking medications known to prolong the QTc interval may require more frequent ECG monitoring. Perform an ECG and correct electrolyte abnormalities prior to starting treatment; do not initiate if QTcF is greater than 480 msec. Monitor ECG at least once weekly for the first 4 weeks of therapy, and at least monthly thereafter.
Immunodeficiency
Moderate:
stiripentol
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.
Liver Disease
Moderate:
stiripentol
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.
Moderate:
ziftomenib
Ziftomenib has a moderate potential interaction with Liver Disease.
The pharmacokinetics of ziftomenib have not been studied in patients with severe liver dysfunction. No adjustment recommended in patients with mild to moderate liver dysfunction.
Long QT Syndrome
Moderate:
ziftomenib
Ziftomenib has a moderate potential interaction with Long QT Syndrome.
Ziftomenib can cause QT (QTc) interval prolongation. Patients with congenital long QTc syndrome, congestive heart failure, electrolyte abnormalities, or who are taking medications known to prolong the QTc interval may require more frequent ECG monitoring. Perform an ECG and correct electrolyte abnormalities prior to starting treatment; do not initiate if QTcF is greater than 480 msec. Monitor ECG at least once weekly for the first 4 weeks of therapy, and at least monthly thereafter.
Malnourishment
Moderate:
stiripentol
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.
Phenylketonuria
Moderate:
stiripentol
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.
Psychosis
Moderate:
stiripentol
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.
Renal Dysfunction
Moderate:
stiripentol
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.
Moderate:
ziftomenib
Ziftomenib has a moderate potential interaction with Renal Dysfunction.
The pharmacokinetics of ziftomenib have not been studied in patients with severe renal dysfunction. No adjustment recommended in patients with mild to moderate renal dysfunction.
Report options
More resources
stiripentol
A total of 649 drugs are known to interact with stiripentol.
- Stiripentol is in the drug class gamma-aminobutyric acid reuptake inhibitors.
- Stiripentol is used to treat Dravet Syndrome.
ziftomenib
A total of 613 drugs are known to interact with ziftomenib.
- Ziftomenib is in the drug class miscellaneous antineoplastics.
- Ziftomenib is used to treat Acute Myeloid Leukemia.
Drug Interaction Classification
| Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit. | |
| Moderately clinically significant. Usually avoid combinations; use it only under special circumstances. | |
| Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan. | |
| No interaction information available. |
Further information
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