Interactions between Pradaxa and Vemurafenib

The dabigatran in Pradaxa has a moderate potential interaction with Antiphospholipid syndrome.

Direct acting oral anticoagulants including factor Xa inhibitors and some thrombin inhibitors as dabigatran, are not recommended for use in patients with antiphospholipid syndrome (APS). Treatment with these drugs has been associated with increased rates of recurrent thrombotic events, especially in patients with triple positive APS.

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).

The dabigatran in Pradaxa has a major potential interaction with Bleeding Disorder.

The use of thrombin inhibitors is contraindicated in the presence of active major bleeding. Additionally, these drugs should be used with caution in patients with disease states associated with an increased risk of bleeding.

The dabigatran in Pradaxa has a major potential interaction with Coagulation Defects and Disorders.

The use of thrombin inhibitors is contraindicated in the presence of active major bleeding. Additionally, these drugs should be used with caution in patients with disease states associated with an increased risk of bleeding.

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.

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).

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.

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.

The dabigatran in Pradaxa has a major potential interaction with Mitral Stenosis.

The use of dabigatran is contraindicated in patients with mechanical prosthetic valves. The use of dabigatran for the prophylaxis of thromboembolic events in patients with atrial fibrillation in the setting of other forms of valvular heart disease, including the presence of a bioprosthetic heart valve has not been studied and it is not recommended.

The dabigatran in Pradaxa has a major potential interaction with Prosthetic Heart Valves - Thrombosis Prophylaxis.

The use of dabigatran is contraindicated in patients with mechanical prosthetic valves. The use of dabigatran for the prophylaxis of thromboembolic events in patients with atrial fibrillation in the setting of other forms of valvular heart disease, including the presence of a bioprosthetic heart valve has not been studied and it is not recommended.

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.

The dabigatran in Pradaxa has a moderate potential interaction with Renal Dysfunction.

The anticoagulant activity and half-life of dabigatran may increase in patients with renal impairment. It is recommended to decrease the dose in patients with severe renal impairment (CrCl 15-30 mL/min). No dose adjustment is recommended in patients with mild or moderate renal impairment. Dosing recommendations for patients with CrCl <15 mL/min or on dialysis has not been established. Care should be exercised when using this agent in patients with renal impairment or on dialysis.

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.

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.