Drug Interaction Report

Lenvatinib has a moderate potential interaction with Arrhythmia.

The use of lenvatinib may cause QT/QTc interval prolongation. It is recommended to monitor and correct electrolyte abnormalities in all patients and to monitor electrocardiograms in patients with congenital long QT syndrome, congestive heart failure, bradyarrhythmias, or those who are taking drugs known to prolong the QT interval, including Class Ia and III antiarrhythmics. Withhold treatment with lenvatinib for the development of QTc interval prolongation greater than 500 ms. and resume treatment at a reduced dose when QTc prolongation resolves to baseline.

Lenvatinib has a moderate potential interaction with Bleeding Disorder.

Hemorrhagic events, including fatal hemorrhagic events have been reported with the use of lenvatinib. It is recommended to withhold treatment and to either resume at a reduced dose or discontinue treatment depending on the severity and persistence of hemorrhage. Discontinue therapy in patients who experience severe or fatal hemorrhagic events. Prior to initiating treatment, consider the risk of severe or fatal hemorrhage associated with tumor invasion/infiltration of major blood vessels (e.g. carotid artery).

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

Tolterodine is associated with anticholinergic central nervous system (CNS) effects. If a patient experiences anticholinergic CNS effects, dose reduction or drug discontinuation should be considered. Tolterodine should be used with caution in patients with Parkinson's disease and in patients with preexisting dementia treated with cholinesterase inhibitors due to the risk of aggravation of symptoms.

Tolterodine has a moderate potential interaction with Dementia.

Tolterodine is associated with anticholinergic central nervous system (CNS) effects. If a patient experiences anticholinergic CNS effects, dose reduction or drug discontinuation should be considered. Tolterodine should be used with caution in patients with Parkinson's disease and in patients with preexisting dementia treated with cholinesterase inhibitors due to the risk of aggravation of symptoms.

Lenvatinib has a moderate potential interaction with Diarrhea.

Cases of diarrhea have been reported with the use of lenvatinib, sometimes leading to interruption of therapy. It is recommended to initiate prompt medical management for the development of diarrhea and to monitor for dehydration. It might be necessary to interrupt treatment with lenvatinib or resume at a reduced dose or permanently discontinue treatment with lenvatinib if severe or fatal diarrhea persists despite medical management. Care and close monitoring is recommended when using this agent in patients presenting diarrhea or at risk of developing diarrhea.

Lenvatinib has a moderate potential interaction with Electrolyte Abnormalities.

The use of lenvatinib may cause QT/QTc interval prolongation. It is recommended to monitor and correct electrolyte abnormalities in all patients and to monitor electrocardiograms in patients with congenital long QT syndrome, congestive heart failure, bradyarrhythmias, or those who are taking drugs known to prolong the QT interval, including Class Ia and III antiarrhythmics. Withhold treatment with lenvatinib for the development of QTc interval prolongation greater than 500 ms. and resume treatment at a reduced dose when QTc prolongation resolves to baseline.

Tolterodine has a major potential interaction with Gastrointestinal Obstruction.

The use of tolterodine is contraindicated in patients with GI obstruction, ileus, or obstructive uropathy. Tolterodine exerts anticholinergic activity by competitive antagonism of muscarinic receptors.

Lenvatinib has a moderate potential interaction with Gastrointestinal Perforation.

Cases of gastrointestinal perforation or fistula have been reported with the use of lenvatinib. Discontinue the use of lenvatinib in patients who develop gastrointestinal perforation or life-threatening fistula. Close monitoring should be exercised when using this agent in patients at risk.

Tolterodine has a major potential interaction with Glaucoma/Intraocular Hypertension.

The use of tolterodine is contraindicated in patients with uncontrolled angle-closure (narrow angle) glaucoma. Tolterodine exerts anticholinergic activity and can result in increased intraocular pressure and loss of accommodation.

Lenvatinib has a moderate potential interaction with Heart Disease.

Cardiac dysfunctions, defined as decreased left or right ventricular function, cardiac failure, or pulmonary edema have been reported with the use of lenvatinib. It is recommended to monitor patients for clinical symptoms or signs of cardiac decompensation. Withhold lenvatinib therapy for development of Grade 3 cardiac dysfunction until improved and either resume at a reduced dose or discontinue its use depending on the severity and persistence of cardiac dysfunction. Discontinue lenvatinib for Grade 4 cardiac dysfunction.

Lenvatinib has a moderate potential interaction with High Blood Pressure.

The use of lenvatinib may cause hypertension. It is recommended to control blood pressure prior to treatment with lenvatinib and monitor blood pressure regularly during treatment as medically indicated. Withhold treatment with lenvatinib for Grade 3 hypertension despite optimal antihypertensive therapy. If clinically appropriate, resume at a reduced dose when hypertension is controlled and discontinue treatment for hypertension that becomes life-threatening. Care and close monitoring of blood pressure is recommended.

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

In clinical trials, arterial thromboembolic events were reported in patients treated with lenvatinib. It is recommended to discontinue lenvatinib following an arterial thrombotic event. Care should be exercised when resuming lenvatinib after an arterial thromboembolic event as its safety has not been established and its use has not been studied in patients who have had an arterial thromboembolic event within the previous 6 months.

Lenvatinib has a moderate potential interaction with Hypocalcemia.

Cases of hypocalcemia have been reported with the use of lenvatinib. It is recommended to monitor blood calcium levels at least monthly and replace calcium as necessary during treatment and to interrupt and adjust dosing as necessary depending on severity, presence of ECG changes, and persistence of hypocalcemia. Care should be exercised when using this agent in patients at risk.

Lenvatinib has a moderate potential interaction with Interstitial Lung Disease.

The use of certain multikinase inhibitors has been associated with pulmonary toxicity. Serious cases of interstitial lung disease (ILD), including fatal cases and interstitial pneumonitis or pulmonary fibrosis have been reported. Caution is recommended when using these agents in patients with a history of interstitial pneumonitis or pulmonary fibrosis or those patients presenting with acute onset of new or progressive unexplained pulmonary symptoms such as dyspnea, cough, and fever pending diagnostic evaluation. If ILD is confirmed, these agents should be permanently discontinued and appropriate measures should be instituted. Treatment should be immediately withheld in patients diagnosed with ILD/pneumonitis and permanently discontinued if no other potential causes of ILD/pneumonitis have been identified.

Lenvatinib has a moderate potential interaction with Liver Disease.

Hepatic failure, including fatal events have been reported with the use of lenvatinib. No dose adjustment is recommended in patients with mild or moderate hepatic impairment. Dose adjustment is needed in patients with severe hepatic impairment. It is recommended to monitor liver function before initiation of therapy with lenvatinib and regularly thereafter as clinically indicated. It might be necessary to temporarily withhold the use of lenvatinib and either resume at a reduced dose or discontinue treatment with lenvatinib depending on the severity and persistence of hepatic impairment. Discontinue treatment with lenvatinib for hepatic failure.

Tolterodine has a moderate potential interaction with Liver Disease.

Tolterodine undergoes biotransformation in the liver of extensive metabolizers to an active metabolite. Poor metabolizers have a greater concentration of active parent and less active metabolite, however the net activity of tolterodine is expected to be the same. The pharmacokinetic disposition of tolterodine can be significantly altered in patients with hepatic dysfunction. Therapy with tolterodine should be administered cautiously in patients with severe hepatic impairment and dosage should be reduced to no greater than 1 mg twice daily.

Tolterodine has a moderate potential interaction with Long QT Syndrome.

Tolterodine has been associated with QT prolongation. The effect on QT interval correlates with plasma concentration of tolterodine. Caution is recommended when prescribing this agent to patients with a known history of QT prolongation or to patients who are taking Class IA (e.g., quinidine, procainamide) or Class III (e.g., amiodarone, sotalol) antiarrhythmic medications.

Tolterodine has a moderate potential interaction with Myasthenia Gravis.

Tolterodine acts as a competitive antagonist of acetylcholine at postganglionic muscarinic receptors. Caution is recommended when using this agent in patients with myasthenia gravis, a disease characterized by decreased cholinergic activity at the neuromuscular junction.

Lenvatinib has a moderate potential interaction with Posterior Reversible Encephalopathy Syndrome.

The use of lenvatinib may cause reversible posterior leukoencephalopathy syndrome (RPLS). Consider this syndrome in any patient presenting with seizures, headache, visual disturbances, confusion or altered mental function. Confirm the diagnosis of RPLS with MRI and if positive, withhold therapy for RPLS until fully resolved. Upon resolution, resume at a reduced dose or discontinue treatment depending on the severity and persistence of neurologic symptoms and administer appropriate treatment as clinically indicated.

Lenvatinib has a moderate potential interaction with Proteinuria.

Proteinuria has been reported with the use of lenvatinib. It is recommended to monitor for proteinuria before initiation of, and periodically throughout treatment. Withhold lenvatinib for >=2 grams of proteinuria/24 hours and resume at a reduced dose when proteinuria is <2 gm/24 hours. Discontinue lenvatinib for nephrotic syndrome.

Lenvatinib has a moderate potential interaction with Pulmonary Edema.

Cardiac dysfunctions, defined as decreased left or right ventricular function, cardiac failure, or pulmonary edema have been reported with the use of lenvatinib. It is recommended to monitor patients for clinical symptoms or signs of cardiac decompensation. Withhold lenvatinib therapy for development of Grade 3 cardiac dysfunction until improved and either resume at a reduced dose or discontinue its use depending on the severity and persistence of cardiac dysfunction. Discontinue lenvatinib for Grade 4 cardiac dysfunction.

Lenvatinib has a moderate potential interaction with Pulmonary Impairment.

The use of certain multikinase inhibitors has been associated with pulmonary toxicity. Serious cases of interstitial lung disease (ILD), including fatal cases and interstitial pneumonitis or pulmonary fibrosis have been reported. Caution is recommended when using these agents in patients with a history of interstitial pneumonitis or pulmonary fibrosis or those patients presenting with acute onset of new or progressive unexplained pulmonary symptoms such as dyspnea, cough, and fever pending diagnostic evaluation. If ILD is confirmed, these agents should be permanently discontinued and appropriate measures should be instituted. Treatment should be immediately withheld in patients diagnosed with ILD/pneumonitis and permanently discontinued if no other potential causes of ILD/pneumonitis have been identified.

Lenvatinib has a moderate potential interaction with Renal Dysfunction.

Cases of renal impairment have been reported with the use of lenvatinib. No dose adjustment is recommended in patients with mild or moderate renal impairment. Dose adjustment is needed in patients with severe renal impairment. It might be necessary to temporarily withhold the use of lenvatinib and either resume at a reduced dose or discontinue treatment with lenvatinib depending on the severity and persistence of renal impairment. Care and close monitoring is recommended when using lenvatinib in patients with end stage renal disease as these patients have not been studied.

Tolterodine has a moderate potential interaction with Renal Dysfunction.

The renal elimination of tolterodine and active metabolite is limited and a prolonged half-life is not anticipated in patients with renal impairment. However, the pharmacokinetic disposition of tolterodine has not been evaluated in patients with renal impairment and it is recommended that tolterodine be administered cautiously in patients with compromised renal function.

Lenvatinib has a moderate potential interaction with Thrombotic/Thromboembolic Disorder.

In clinical trials, arterial thromboembolic events were reported in patients treated with lenvatinib. It is recommended to discontinue lenvatinib following an arterial thrombotic event. Care should be exercised when resuming lenvatinib after an arterial thromboembolic event as its safety has not been established and its use has not been studied in patients who have had an arterial thromboembolic event within the previous 6 months.

Lenvatinib has a moderate potential interaction with Underactive Thyroid.

The use of lenvatinib impairs exogenous thyroid suppression and may cause hypothyroidism. It is recommended to monitor thyroid function before initiation of, and at least monthly throughout, treatment with lenvatinib. Care should be taken when using this agent in patients with thyroid dysfunction and treatment of hypothyroidism should be made according to standard medical practice to maintain a euthyroid state.

Tolterodine has a major potential interaction with Urinary Retention.

The use of tolterodine is contraindicated in patients with GI obstruction, ileus, or obstructive uropathy. Tolterodine exerts anticholinergic activity by competitive antagonism of muscarinic receptors.