Interactions between Isavuconazonium and Trametinib

Trametinib has a moderate potential interaction with Bleeding Disorder.

The use of trametinib may increase the incidence of hemorrhagic events, including major hemorrhages defined as symptomatic bleeding in a critical area or organ. It is recommended to discontinue the use of trametinib for all Grade 4 hemorrhagic events and temporarily withhold the use of trametinib for Grade 3 hemorrhagic events, if improved, resume the dose at the next lower dose level. Close monitoring is recommended. Care should be taken when using this agent in patients at risk.

Trametinib has a moderate potential interaction with Cardiomyopathy.

Cardiomyopathy, including cardiac failure may occur with the use of trametinib. It is recommended that all patients undergo a cardiovascular evaluation including echocardiogram at baseline to document normal left ventricular ejection fraction (LVEF) and repeat echocardiograms at Week 4, Week 12, and every 12 weeks thereafter as clinically appropriate. Withhold trametinib for up to 4 weeks if absolute LVEF value decreases by 10% from pretreatment values and is less than the lower limit of normal (LLN). Permanently discontinue trametinib for symptomatic cardiomyopathy or persistent, asymptomatic LV dysfunction of >20% from baseline that is below LLN and that does not resolve within 4 weeks.

Trametinib has a moderate potential interaction with Diabetes Mellitus.

The use of trametinib may cause hyperglycemia. It is recommended to monitor serum glucose levels upon initiation of therapy and as clinically appropriate in patients with preexisting diabetes or hyperglycemia.

Trametinib has a moderate potential interaction with Gastrointestinal Perforation.

Colitis and gastrointestinal perforation, sometimes with fatal outcomes can occur with the use of trametinib. Care and close monitoring is recommended with using this agent in patients with gastrointestinal complications. Monitor patients closely for colitis and gastrointestinal perforations.

Trametinib has a moderate potential interaction with Heart Failure.

Cardiomyopathy, including cardiac failure may occur with the use of trametinib. It is recommended that all patients undergo a cardiovascular evaluation including echocardiogram at baseline to document normal left ventricular ejection fraction (LVEF) and repeat echocardiograms at Week 4, Week 12, and every 12 weeks thereafter as clinically appropriate. Withhold trametinib for up to 4 weeks if absolute LVEF value decreases by 10% from pretreatment values and is less than the lower limit of normal (LLN). Permanently discontinue trametinib for symptomatic cardiomyopathy or persistent, asymptomatic LV dysfunction of >20% from baseline that is below LLN and that does not resolve within 4 weeks.

Trametinib 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.

Isavuconazonium has a moderate potential interaction with Liver Disease.

The use of isavuconazonium has been associated with hepatic adverse reactions (e.g., elevations in ALT, AST, alkaline phosphatase, total bilirubin). Cases of more severe hepatic reactions (including hepatitis, cholestasis, hepatic failure including death) have been reported during therapy in patients with serious underlying medical conditions (e.g., hematologic malignancy). Liver-related laboratory tests should be evaluated at the start and during therapy. Isavuconazonium has not been studied in patients with severe liver dysfunction (Child-Pugh C) and should be used in these patients only when the benefits outweigh the risk. Clinical monitoring for drug-related side effects is recommended when treating patients with severe liver dysfunction.

Trametinib has a moderate potential interaction with Liver Disease.

Based on a population pharmacokinetic analysis of trametinib, no dose adjustment is recommended in patients with mild hepatic impairment. There are no data on the pharmacokinetics of trametinib in patients with moderate or severe hepatic impairment. Close monitoring is recommended for these patients.

Trametinib has a moderate potential interaction with Noninfectious Colitis.

Colitis and gastrointestinal perforation, sometimes with fatal outcomes can occur with the use of trametinib. Care and close monitoring is recommended with using this agent in patients with gastrointestinal complications. Monitor patients closely for colitis and gastrointestinal perforations.

Trametinib 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.

Trametinib has a moderate potential interaction with Renal Dysfunction.

Based on a population pharmacokinetic analysis of trametinib, no dose adjustment is recommended in patients with mild or moderate renal impairment. There are no data on the pharmacokinetics of trametinib in patients with severe renal impairment. Close monitoring is recommended for these patients.

Isavuconazonium has a major potential interaction with Short QT Syndrome.

Isavuconazonium shortened the QTc interval in a concentration-related manner. This drug is contraindicated in patients with familial short QT syndrome.

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

Venous thromboembolism can occur with trametinib. It is recommended to permanently discontinue the use of trametinib for life threatening pulmonary embolism and to withhold therapy for uncomplicated deep venous thrombosis and pulmonary embolism for up to 3 weeks or as clinically appropriate and if improved patients should resume treatment at a lower dose as clinically indicated. Care should be exercised when using this agent in patients at risk.

Trametinib has a moderate potential interaction with Ventricular Arrhythmia.

Cardiomyopathy, including cardiac failure may occur with the use of trametinib. It is recommended that all patients undergo a cardiovascular evaluation including echocardiogram at baseline to document normal left ventricular ejection fraction (LVEF) and repeat echocardiograms at Week 4, Week 12, and every 12 weeks thereafter as clinically appropriate. Withhold trametinib for up to 4 weeks if absolute LVEF value decreases by 10% from pretreatment values and is less than the lower limit of normal (LLN). Permanently discontinue trametinib for symptomatic cardiomyopathy or persistent, asymptomatic LV dysfunction of >20% from baseline that is below LLN and that does not resolve within 4 weeks.

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

Ocular toxicities, including retinal vein occlusion (RVO), retinal pigment epithelial detachment (RPED) have been reported with the use of trametinib. It is recommended to perform ophthalmological evaluation periodically and at any time a patient reports visual disturbances. Permanently discontinue treatment with trametinib in patients with documented RVO, or RPED. Withhold therapy with trametinib if RPED is diagnosed. If resolution of the RPED is documented on repeat ophthalmological evaluation within 3 weeks, resume treatment or reduce the dose or discontinue treatment if no improvement.