Drug Interaction Report

Consumer information for this interaction is not currently available.

MONITOR: Coadministration with drugs that are inhibitors of CYP450 2D6 may increase the plasma concentrations of tolterodine, which is primarily metabolized by this isoenzyme in most patients (referred to as "extensive metabolizers") to an active metabolite, 5-hydroxymethyl tolterodine (5-HMT), that is equipotent to tolterodine. A subset of the population (about 7%) is devoid of CYP450 2D6 (referred to as "poor metabolizers") and uses CYP450 3A4 to metabolize tolterodine to an inactive metabolite instead. In a study to assess this interaction, fluoxetine (a potent CYP450 2D6 inhibitor) was administered concurrently with immediate release tolterodine. It was observed that fluoxetine significantly inhibited the metabolism of tolterodine immediate release in extensive metabolizers, resulting in a 4.8-fold increase in tolterodine systemic exposure (AUC). There was a 52% decrease in the peak plasma concentration (Cmax) and a 20% decrease in the AUC of tolterodine's active metabolite. During this interaction the sums of unbound serum concentrations of tolterodine and 5-HMT are about 25% higher, meaning little alteration in the overall pharmacological activity of tolterodine is expected. Therefore, some authorities suggest that the interaction is not clinically significant. However, increased plasma concentrations may increase the risk of anticholinergic adverse effects associated with tolterodine. Additionally, since 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 2D6 inhibitor being used also carries a risk of QT prolongation (e.g., fluoxetine, ranolazine, certain phenothiazines such as chlorpromazine). Data are not available for less potent CYP450 2D6 inhibitors.

MANAGEMENT: During concomitant therapy with drugs that inhibit CYP450 2D6 activity, the possibility of prolonged and/or increased pharmacologic effects of tolterodine should be considered. Increased monitoring may be particularly important when the CYP450 2D6 inhibitor has a similar adverse effect profile to that of tolterodine or when its inhibitory effects are long lasting (e.g., rolapitant can increase the plasma concentrations and risk of adverse effects of CYP450 2D6 substrates for at least 28 days). 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.

Information for this minor interaction is available on the professional version.

Do not use alcohol or medications that contain alcohol while you are receiving treatment with propoxyphene. This may increase nervous system side effects such as drowsiness, dizziness, lightheadedness, difficulty concentrating, and impairment in thinking and judgment. In severe cases, low blood pressure, respiratory distress, fainting, coma, or even death may occur. Do not use more than the recommended dose of propoxyphene, and avoid activities requiring mental alertness such as driving or operating hazardous machinery until you know how the medication affects you. It is important to tell your doctor about all other medications you use, including vitamins and herbs. Do not stop using any medication without first talking to your doctor.

Ask your doctor before using acetaminophen together with ethanol (alcohol). This can cause serious side effects that affect your liver. Call your doctor immediately if you experience a fever, chills, joint pain or swelling, excessive tiredness or weakness, unusual bleeding or bruising, skin rash or itching, loss of appetite, nausea, vomiting, or yellowing of the skin or the whites of your eyes. If your doctor does prescribe these medications together, you may need a dose adjustment or special tests to safely take 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.

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.