Drug Interaction Report

Vemurafenib has a moderate potential interaction with Arrhythmia.

Vemurafenib can cause dose dependent QT prolongation which may lead to an increased risk for ventricular arrhythmias, including Torsade de Pointes. It is recommended not to start treatment in patients with uncorrectable electrolyte abnormalities, QTc > 500 ms, or long QT syndrome, or in patients who are taking medicinal products known to prolong the QT interval. Evaluate patients prior to and following treatment initiation or after dose modification for QTc prolongation, evaluate ECG and electrolytes (including potassium, magnesium, and calcium) periodically, and thereafter as clinically indicated. Vemurafenib should be withhold in patients who develop QTc > 500 ms. Upon recovery to QTc <= 500 ms, restart at a reduced dose and it should be permanently discontinued if the QTc interval remains > 500 ms and increased > 60 ms from pre-treatment values after controlling cardiac risk factors for QT prolongation (e.g., electrolyte abnormalities, congestive heart failure, and bradyarrhythmias).

Vemurafenib has a moderate potential interaction with Dermatitis, Drug-Induced.

Severe dermatologic reactions, including Stevens-Johnson syndrome, toxic epidermal necrolysis, and mild to severe photosensitivity can occur in patients treated with vemurafenib. Consider dose modifications for intolerable >= Grade 2 photosensitivity. It is recommended to advise patients to avoid sun exposure, wear protective clothing and use a broad-spectrum UVA/UVB sunscreen and a suitable lip balm when outdoors while on vemurafenib treatment. Permanently discontinue vemurafenib in patients who experience a severe dermatologic reaction.

Levalbuterol has a moderate potential interaction with Diabetes Mellitus.

Adrenergic bronchodilators may cause increases in blood glucose concentrations. These effects are usually transient and slight, but may be significant with dosages higher than those normally recommended. Large doses of IV albuterol (not commercially available in the U.S.) and terbutaline sulfate have been reported to cause exacerbation of preexisting diabetes mellitus and ketoacidosis. Therapy with adrenergic bronchodilators should be administered cautiously in patients with diabetes mellitus. Closer monitoring of blood glucose concentrations may be appropriate. Systemic adverse effects are minimized, but not abolished, by administration of these agents via oral inhalation.

Vemurafenib has a moderate potential interaction with Electrolyte Abnormalities.

Vemurafenib can cause dose dependent QT prolongation which may lead to an increased risk for ventricular arrhythmias, including Torsade de Pointes. It is recommended not to start treatment in patients with uncorrectable electrolyte abnormalities, QTc > 500 ms, or long QT syndrome, or in patients who are taking medicinal products known to prolong the QT interval. Evaluate patients prior to and following treatment initiation or after dose modification for QTc prolongation, evaluate ECG and electrolytes (including potassium, magnesium, and calcium) periodically, and thereafter as clinically indicated. Vemurafenib should be withhold in patients who develop QTc > 500 ms. Upon recovery to QTc <= 500 ms, restart at a reduced dose and it should be permanently discontinued if the QTc interval remains > 500 ms and increased > 60 ms from pre-treatment values after controlling cardiac risk factors for QT prolongation (e.g., electrolyte abnormalities, congestive heart failure, and bradyarrhythmias).

Levalbuterol has a moderate potential interaction with Heart Disease.

Adrenergic bronchodilators can stimulate cardiovascular beta- 1 and beta- 2 receptors, resulting in adverse effects such as tachycardia, palpitation, peripheral vasodilation, blood pressure changes, and ECG changes (e.g., flattening of the T wave; prolongation of the QT interval; ST segment depression). Direct stimulation of cardiac tissues is mediated by beta- 1 receptors and thus less likely to occur with beta-2-selective agents such as albuterol. However, beta-2-selectivity is not absolute and can be lost with larger doses. High dosages of these agents have been associated with precipitation or aggravation of angina, myocardial ischemia, and cardiac arrhythmias. Therapy with adrenergic bronchodilators should be administered cautiously in patients with sensitivity to sympathomimetic amines, hyperthyroidism, and/or underlying cardiovascular disorders such as coronary insufficiency, cardiac arrhythmias, or hypertension. The recommended dosages should not be exceeded.

Levalbuterol has a moderate potential interaction with High Blood Pressure.

Adrenergic bronchodilators can stimulate cardiovascular beta- 1 and beta- 2 receptors, resulting in adverse effects such as tachycardia, palpitation, peripheral vasodilation, blood pressure changes, and ECG changes (e.g., flattening of the T wave; prolongation of the QT interval; ST segment depression). Direct stimulation of cardiac tissues is mediated by beta- 1 receptors and thus less likely to occur with beta-2-selective agents such as albuterol. However, beta-2-selectivity is not absolute and can be lost with larger doses. High dosages of these agents have been associated with precipitation or aggravation of angina, myocardial ischemia, and cardiac arrhythmias. Therapy with adrenergic bronchodilators should be administered cautiously in patients with sensitivity to sympathomimetic amines, hyperthyroidism, and/or underlying cardiovascular disorders such as coronary insufficiency, cardiac arrhythmias, or hypertension. The recommended dosages should not be exceeded.

Vemurafenib has a moderate potential interaction with History, Skin Cancer.

Cutaneous squamous cell carcinoma, keratoacanthoma, and melanoma occurred at a higher incidence in patients receiving vemurafenib. Potential risk factors associated included age (> 65 years), prior skin cancer, and chronic sun exposure. It is recommended to perform dermatologic evaluations prior to initiation of therapy and periodically thereafter as clinically indicated. Consider dermatologic monitoring for 6 months following discontinuation of vemurafenib.

Levalbuterol has a moderate potential interaction with Hyperthyroidism.

Adrenergic bronchodilators can stimulate cardiovascular beta- 1 and beta- 2 receptors, resulting in adverse effects such as tachycardia, palpitation, peripheral vasodilation, blood pressure changes, and ECG changes (e.g., flattening of the T wave; prolongation of the QT interval; ST segment depression). Direct stimulation of cardiac tissues is mediated by beta- 1 receptors and thus less likely to occur with beta-2-selective agents such as albuterol. However, beta-2-selectivity is not absolute and can be lost with larger doses. High dosages of these agents have been associated with precipitation or aggravation of angina, myocardial ischemia, and cardiac arrhythmias. Therapy with adrenergic bronchodilators should be administered cautiously in patients with sensitivity to sympathomimetic amines, hyperthyroidism, and/or underlying cardiovascular disorders such as coronary insufficiency, cardiac arrhythmias, or hypertension. The recommended dosages should not be exceeded.

Levalbuterol has a moderate potential interaction with Hypokalemia.

Adrenergic bronchodilators may cause decreases in serum potassium concentrations, primarily when given by nebulization or intravenous administration. Although this effect is usually transient and does not require supplementation, clinically significant hypokalemia may occur in some patients, with the potential to induce cardiovascular adverse effects. The relevance of these observations to oral or oral aerosol/powder for inhalation therapy is unknown. Therapy with adrenergic bronchodilators should be administered cautiously in patients with or predisposed to hypokalemia.

Vemurafenib 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.

Vemurafenib has a moderate potential interaction with Liver Disease.

Liver injury leading to functional hepatic impairment, including coagulopathy or other organ dysfunction may occur with the use of vemurafenib. Based on a population pharmacokinetic analysis to evaluate the effect of hepatic impairment, no dose adjustment is recommended for patients with mild and moderate hepatic impairment. The appropriate dose of vemurafenib has not been established in patients with severe hepatic impairment. It is recommended to monitor transaminases, alkaline phosphatase, and bilirubin before initiation of treatment and monthly during treatment, or as clinically indicated; and to manage laboratory abnormalities with dose reduction, treatment interruption, or treatment discontinuation as appropriate.

Vemurafenib 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.

Levalbuterol has a moderate potential interaction with Renal Dysfunction.

Levalbuterol is substantially excreted by the kidney, and the risk of toxic reactions may be greater in patients with impaired renal function. Care should be taken in dose selection in patients with renal impairment and it may be useful to monitor renal function.

Vemurafenib has a moderate potential interaction with Renal Dysfunction.

Renal failure, including acute interstitial nephritis and acute tubular necrosis may occur with the use of vemurafenib. Based on a population pharmacokinetic analysis, no dose adjustment is recommended for patients with mild and moderate renal impairment. The appropriate dose of vemurafenib has not been established in patients with severe renal impairment. It is recommended to measure serum creatinine before initiation of therapy and periodically during treatment.

Levalbuterol has a moderate potential interaction with Seizures.

Adrenergic bronchodilators may cause CNS stimulation. Therapy with adrenergic bronchodilators should be administered cautiously in patients with seizure disorders. Systemic adverse effects are minimized, but not abolished, by administration of these agents via oral inhalation.

Vemurafenib has a moderate potential interaction with Skin Cancer.

Cutaneous squamous cell carcinoma, keratoacanthoma, and melanoma occurred at a higher incidence in patients receiving vemurafenib. Potential risk factors associated included age (> 65 years), prior skin cancer, and chronic sun exposure. It is recommended to perform dermatologic evaluations prior to initiation of therapy and periodically thereafter as clinically indicated. Consider dermatologic monitoring for 6 months following discontinuation of vemurafenib.

Vemurafenib has a moderate potential interaction with Visual Defect/Disturbance.

Uveitis, blurry vision, and photophobia can occur in patients treated with vemurafenib. Monitor patients for signs and symptoms of uveitis. Care must be exercised when using this agent in patients with ophthalmological complications.