Interactions between Austedo XR and Crizotinib

The deutetrabenazine in Austedo XR has a major potential interaction with Arrhythmia.

The use of deutetrabenazine should be avoided in patients with congenital long QT syndrome and in patients with a history of cardiac arrhythmias.

Crizotinib has a moderate potential interaction with Arrhythmia.

Crizotinib can cause symptomatic bradycardia. Heart rate and blood pressure should be monitored regularly. It is recommended to withhold, reduce dose, or permanently discontinue crizotinib for bradycardia as recommended.

Crizotinib has a moderate potential interaction with Arrhythmia.

The use of crizotinib can cause QTc prolongation. It is recommended to avoid the use of this agent in patients with congenital long QT syndrome. Care should be exercised when using this drug in patients with a history of or predisposition to QTc prolongation. ECGs and electrolytes should be monitored in patients with congestive heart failure, bradyarrhythmias, electrolyte abnormalities, or who are taking medications that prolong the QT interval. It is recommended to withhold, reduce dose, or permanently discontinue crizotinib for QT/QTc interval prolongation as recommended.

The deutetrabenazine in Austedo XR has a major potential interaction with Depression.

The use of deutetrabenazine is contraindicated in patients with Huntington's disease who are suicidal, or have untreated or uncontrolled depression. Deutetrabenazine can increase the risk of depression and suicidal thoughts and behavior in these patients. Particular caution should be exercised in treating patients with a history of depression or prior suicide attempts or ideation.

Crizotinib has a moderate potential interaction with Diverticulitis.

The use of crizotinib can cause gastrointestinal (GI) perforations. This drug should be used with caution in patients at risk for GI perforation (e.g., history of diverticulitis, metastases to the gastrointestinal tract, concomitant use of medicinal products with a recognized risk of gastrointestinal perforation). It is recommended to discontinue treatment in patients who develop GI perforation.

Crizotinib has a moderate potential interaction with Electrolyte Abnormalities.

The use of crizotinib can cause QTc prolongation. It is recommended to avoid the use of this agent in patients with congenital long QT syndrome. Care should be exercised when using this drug in patients with a history of or predisposition to QTc prolongation. ECGs and electrolytes should be monitored in patients with congestive heart failure, bradyarrhythmias, electrolyte abnormalities, or who are taking medications that prolong the QT interval. It is recommended to withhold, reduce dose, or permanently discontinue crizotinib for QT/QTc interval prolongation as recommended.

Crizotinib has a moderate potential interaction with Gastrointestinal Obstruction.

The use of crizotinib can cause gastrointestinal (GI) perforations. This drug should be used with caution in patients at risk for GI perforation (e.g., history of diverticulitis, metastases to the gastrointestinal tract, concomitant use of medicinal products with a recognized risk of gastrointestinal perforation). It is recommended to discontinue treatment in patients who develop GI perforation.

Crizotinib has a moderate potential interaction with Gastrointestinal Perforation.

The use of crizotinib can cause gastrointestinal (GI) perforations. This drug should be used with caution in patients at risk for GI perforation (e.g., history of diverticulitis, metastases to the gastrointestinal tract, concomitant use of medicinal products with a recognized risk of gastrointestinal perforation). It is recommended to discontinue treatment in patients who develop GI perforation.

Crizotinib has a moderate potential interaction with Heart Failure.

The use of crizotinib can cause QTc prolongation. It is recommended to avoid the use of this agent in patients with congenital long QT syndrome. Care should be exercised when using this drug in patients with a history of or predisposition to QTc prolongation. ECGs and electrolytes should be monitored in patients with congestive heart failure, bradyarrhythmias, electrolyte abnormalities, or who are taking medications that prolong the QT interval. It is recommended to withhold, reduce dose, or permanently discontinue crizotinib for QT/QTc interval prolongation as recommended.

Crizotinib has a moderate potential interaction with Interstitial Lung Disease.

Severe, life-threatening, or fatal interstitial lung disease (ILD)/pneumonitis can occur with crizotinib. Care should be exercised when using this drug in patients with preexisting pulmonary impairment. Patients should be monitored for pulmonary symptoms indicative of ILD/pneumonitis. Crizotinib should be permanently discontinued in patients diagnosed with drug-related ILD/pneumonitis if no other potential causes of ILD/pneumonitis have been identified.

The deutetrabenazine in Austedo XR has a major potential interaction with Liver Disease.

The use of deutetrabenazine is contraindicated in patients with hepatic impairment. The effect of hepatic impairment on the pharmacokinetics of deutetrabenazine and its primary metabolites has not been studied; however, in a clinical study conducted with a closely related VMAT2 inhibitor, there was a large increase in exposure to this drug and its active metabolites in patients with hepatic impairment.

Crizotinib has a moderate potential interaction with Liver Disease.

Crizotinib concentrations increased in patients with preexisting moderate (any AST and total bilirubin greater than 1.5 to 3 times the upper limit of normal [1.5 to 3 x ULN]) or severe (any AST and total bilirubin greater than 3 x ULN) liver dysfunction; a reduced dosage of crizotinib is recommended in these patients. Caution is recommended in patients with moderate or severe liver dysfunction. No dose adjustment is recommended in patients with preexisting mild liver dysfunction (AST greater than ULN and total bilirubin up to 1 x ULN or any AST and total bilirubin greater than 1 to 1.5 x ULN).

Cases of drug-induced hepatotoxicity with fatal outcomes have been reported with the use of crizotinib. It is recommended to monitor liver function tests (including ALT, AST, total bilirubin) every 2 weeks during the first 2 months of therapy, then once a month, and as clinically indicated, with more frequent repeat testing for increased liver transaminases, alkaline phosphatase, or total bilirubin in patients who develop increased transaminases. It is recommended to withhold, reduce dose, or permanently discontinue crizotinib for hepatotoxicity as recommended.

The deutetrabenazine in Austedo XR has a moderate potential interaction with Neuroleptic Malignant Syndrome.

Neuroleptic Malignant Syndrome (NMS) has been reported in association with drugs that reduce dopaminergic transmission such as, deutetrabenazine. Deutetrabenazine should be used with caution in patients presenting similar signs and symptoms of NMS. Clinicians should be alerted to the signs and symptoms associated with NMS. Recurrence of NMS has been reported with resumption of drug therapy. If treatment with deutetrabenazine is needed after recovery from NMS, patients should be monitored for signs of recurrence.

The deutetrabenazine in Austedo XR has a moderate potential interaction with Parkinsonism.

The use of vesicular monoamine transporter 2 (VMAT2) inhibitor, such as valbenazine and deutetrabenazine may cause parkinsonism in patients with tardive dyskinesia. These agents should be used with caution in patients with parkinson disease or those presenting with parkinson-like symptoms such as, falls, gait disturbances, tremor, drooling and hypokinesia. It is recommended to reduce the dose or to discontinue treatment in patients who develop clinically significant parkinson-like signs or symptoms while on treatment with these agents.

Crizotinib has a moderate potential interaction with Pulmonary Impairment.

Severe, life-threatening, or fatal interstitial lung disease (ILD)/pneumonitis can occur with crizotinib. Care should be exercised when using this drug in patients with preexisting pulmonary impairment. Patients should be monitored for pulmonary symptoms indicative of ILD/pneumonitis. Crizotinib should be permanently discontinued in patients diagnosed with drug-related ILD/pneumonitis if no other potential causes of ILD/pneumonitis have been identified.

Crizotinib has a moderate potential interaction with Renal Dysfunction.

The exposure to crizotinib is increased in patients with preexisting severe renal dysfunction (CrCl less than 30 mL/min [calculated using the modified Cockcroft-Gault equation for adult patients and the Schwartz equation for pediatric patients]) not requiring dialysis; a reduced dosage of crizotinib is recommended in these patients. Care should be exercised when using this drug in patients with severe renal dysfunction not requiring dialysis. No dose adjustment is recommended in patients with mild to moderate renal dysfunction (CrCl 30 to 89 mL/min).

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

Cases of optic atrophy and optic nerve disorder leading to vision loss have been reported with the use of crizotinib. Assessment of visual symptoms for all patients is recommended monthly during therapy; new visual symptoms should be reported to an eye specialist. For pediatric and young adult patients with anaplastic large cell lymphoma or inflammatory myofibroblastic tumor, baseline and follow-up ophthalmologic examinations (including retinal examination) should be obtained within 1 month of starting crizotinib and every 3 months thereafter. The ophthalmological evaluation should consist of best corrected visual acuity, retinal photographs, visual fields, optical coherence tomography (OCT), and other evaluations as appropriate. Crizotinib should be permanently discontinued for grade 3 or 4 ocular disorders or severe visual loss (best corrected vision less than 20/200 in 1 or both eyes) unless another cause is identified. There is insufficient information to characterize the risks of resumption of crizotinib in patients who develop visual symptoms or visual loss; a decision to resume treatment with crizotinib should consider the potential benefits versus risks to the patient.