Drug Interaction Report

Consumer information for this interaction is not currently available.

MONITOR: Coadministration with drugs that are inhibitors of CYP450 3A4 may increase the plasma concentrations of tolterodine, which is partially metabolized by the isoenzyme. Tolterodine is primarily metabolized by CYP450 2D6 in most patients (referred to as "extensive metabolizers" or "EMs") to an equipotent, active metabolite, 5-hydroxymethyl tolterodine (5-HMT). However, in patients who are CYP450 2D6-deficient, or so-called "poor metabolizers" or "PMs" of CYP450 2D6 (approximately 7% of Caucasians and less than 2% of Asians and individuals of African descent), tolterodine is primarily metabolized by CYP450 3A4 to N-dealkylated tolterodine. Coadministration of tolterodine with ketoconazole 200 mg daily, a potent CYP450 3A4 inhibitor, increased the tolterodine mean peak plasma concentration (Cmax) by 2-fold and the mean systemic concentrations (AUC) by 2.5-fold in PMs. Data are not available for coadministration of tolterodine with CYP450 3A4 inhibitors in EMs or less potent CYP450 3A4 inhibitors. As tolterodine causes concentration-dependent QT interval prolongation, an increase in its AUC could increase the possibility of experiencing this adverse effect. Likewise, this risk may be further increased if the CYP450 3A4 inhibitor being used also carries a risk of QT prolongation (e.g., asciminib, bepridil, ciprofloxacin, clofazimine, crizotinib, erythromycin, fluconazole, lapatinib, pazopanib, rucaparib).

MANAGEMENT: Caution is advised when tolterodine is used with CYP450 3A4 inhibitors. Clinical and laboratory monitoring, including QTc interval and serum electrolytes, is advised. Patients should have regular ECGs and be monitored for arrhythmias when the QTc interval is prolonged. If the QTc interval becomes markedly prolonged or symptoms of arrhythmia occur, drug discontinuation should be considered. 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. Patients should be advised to notify their physician if they experience new or worsening side effects of tolterodine including severe blurry vision, difficulty urinating, dry mouth, headache, drowsiness, dizziness, or GI upset.

Stiripentol should be taken during a meal to help with its absorption; however, it should not be taken with milk, dairy products (e.G., yogurt, soft cream cheese), fruit juice, or carbonated (fizzy) beverages. Also avoid or limit the use of alcohol because it can increase side effects of stiripentol such as dizziness and drowsiness. Patients should not engage in 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, since stiripentol may affect the clearance of these substances from the body. Some medications may also contain caffeine, so check product labels to verify the ingredients before taking, or ask a pharmacist or other healthcare provider for assistance. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medications without first talking to your doctor.