Drug Interactions between ephedrine / hydroxyzine / theophylline and sebetralstat

Consumer information for this interaction is not currently available.

GENERALLY AVOID: Coadministration with grapefruit juice may increase the plasma concentrations of sebetralstat. The mechanism is decreased clearance of sebetralstat due to inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruits. The interaction has not been studied with grapefruit juice but has been reported for the potent CYP450 3A4 inhibitor, itraconazole. In a clinical study, sebetralstat peak plasma concentration (Cmax) and systemic exposure (AUC) increased by 2.4-fold and 5.2-fold, respectively, following concomitant administration of the potent CYP450 3A4 inhibitor, itraconazole (200 mg once daily for 6 days). 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. Increased exposure to sebetralstat may increase the risk and/or severity of adverse effects such as headache and QT prolongation. The use of sebetralstat alone at doses 2.5 times the maximum recommended dose has been associated with a mean increase in corrected QT (QTc) interval of 10.4 msec. Although clinical data are lacking for sebetralstat, in general, prolongation of the QT interval may increase the risk of ventricular arrhythmias such as ventricular tachycardia and torsade de pointes.

MANAGEMENT: Consumption of food or drinks containing grapefruit should generally be avoided during treatment with sebetralstat.

Both smoking and excessive caffeine consumption can alter the blood levels of theophylline, which may affect the dosing. Tobacco and marijuana smoke (including secondhand exposure) generally reduces, while caffeine increases, blood levels. In addition, caffeine is a stimulant and may add to the side effects of theophylline such as headache, insomnia, and increases in blood pressure and heart rate. It is best to avoid smoking and to limit caffeine consumption during theophylline therapy. Talk to a healthcare professional if you have any questions or concerns. If you start smoking or undergo smoking cessation, your doctor may need to monitor your blood levels more closely to determine if you need a dose adjustment of theophylline. You should stop taking theophylline and seek medical attention if you experience potential signs and symptoms of excessive drug levels such as nausea, vomiting, persistent headache, insomnia, and rapid heartbeat. 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.

When theophylline is given with enteral (tube) feedings, blood levels may be decreased due to interference with its absorption. This may reduce the effectiveness of the medication. To minimize potential for interaction, you may interrupt the feeding for one hour before and one hour after the theophylline dose. You may need more frequent blood tests to monitor theophylline levels.

Alcohol can increase the nervous system side effects of hydrOXYzine such as dizziness, drowsiness, and difficulty concentrating. Some people may also experience impairment in thinking and judgment. You should avoid or limit the use of alcohol while being treated with hydrOXYzine. Do not use more than the recommended dose of hydrOXYzine, and avoid activities requiring mental alertness such as driving or operating hazardous machinery until you know how the medication affects you. Talk to your doctor or pharmacist if you have any questions or concerns.

Ask your doctor before using theophylline together with caffeine. Using these medications together may increase some of the side effects of theophylline. This can cause nausea, vomiting, insomnia, tremors, restlessness, uneven heartbeats, and seizure (convulsions). Avoid drinks or foods that contain caffeine, such as coffee, tea, cola, and chocolate. You may need a dose adjustment or special test if you use both medications. 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.

Both ePHEDrine and caffeine can increase blood pressure and heart rate, and combining them may enhance these effects. Talk to your doctor before using these medications, especially if you have a history of high blood pressure or heart disease. You may need a dose adjustment or more frequent monitoring by your doctor to safely use both medications. Contact your doctor if your condition changes or you experience increased side effects. 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.

Consumer information for this interaction is not currently available.

MONITOR: Smoking cessation may lead to elevated plasma concentrations and enhanced pharmacologic effects of drugs that are substrates of CYP450 1A2 (and possibly CYP450 1A1) and/or certain drugs with a narrow therapeutic index (e.g., flecainide, pentazocine). One proposed mechanism is related to the loss of CYP450 1A2 and 1A1 induction by polycyclic aromatic hydrocarbons in tobacco smoke; when smoking cessation agents are initiated and smoking stops, the metabolism of certain drugs may decrease leading to increased plasma concentrations. The mechanism by which smoking cessation affects narrow therapeutic index drugs that are not known substrates of CYP450 1A2 or 1A1 is unknown. The clinical significance of this interaction is unknown as clinical data are lacking.

MANAGEMENT: Until more information is available, caution is advisable if smoking cessation agents are used concomitantly with drugs that are substrates of CYP450 1A2 or 1A1 and/or those with a narrow therapeutic range. Patients receiving smoking cessation agents may require periodic dose adjustments and closer clinical and laboratory monitoring of medications that are substrates of CYP450 1A2 or 1A1.