Interactions between Midostaurin and VESIcare
1 drug interaction and 13 additional warnings found for the following 2 drugs:
- midostaurin
- VESIcare (solifenacin)
Drug interactions
Moderate drug interactions
Moderate:
solifenacin midostaurin
Applies to: VESIcare (solifenacin) and midostaurin
Monitor
Theoretically, concurrent use of two or more drugs that can cause QT interval prolongation may result in additive effects and increased risk of ventricular arrhythmias including torsade de pointes and sudden death. The risk of an individual agent or a combination of these agents causing ventricular arrhythmia in association with QT prolongation is largely unpredictable but may be increased by certain underlying risk factors such as congenital long QT syndrome, cardiac disease, and electrolyte disturbances (e.g., hypokalemia, hypomagnesemia). In addition, the extent of drug-induced QT prolongation is dependent on the particular drug(s) involved and dosage(s) of the drug(s).
Management
Caution and clinical monitoring are recommended if multiple agents associated with QT interval prolongation are prescribed together. Patients should be advised to seek prompt medical attention if they experience symptoms that could indicate the occurrence of torsade de pointes such as dizziness, lightheadedness, fainting, palpitation, irregular heart rhythm, shortness of breath, or syncope.
References (7)
- Glassman AH, Bigger JT Jr (2001) "Antipsychotic drugs: prolonged QTc interval, torsade de pointes, and sudden death." Am J Psychiatry, 158, p. 1774-82
- Witchel HJ, Hancox JC, Nutt DJ (2003) "Psychotropic drugs, cardiac arrhythmia, and sudden death." J Clin Psychopharmacol, 23, p. 58-77
- Iannini PB (2002) "Cardiotoxicity of macrolides, ketolides and fluoroquinolones that prolong the QTc interval." Expert Opin Drug Saf, 1, p. 121-8
- Cerner Multum, Inc. "UK Summary of Product Characteristics."
- Canadian Pharmacists Association (2006) e-CPS. http://www.pharmacists.ca/function/Subscriptions/ecps.cfm?link=eCPS_quikLink
- Cerner Multum, Inc. "Australian Product Information."
- EMA. European Medicines Agency. European Union (2013) EMA - List of medicines under additional monitoring. http://www.ema.europa.eu/ema/index.jsp?curl=pages/regulation/document_listing/document_listing_000366.jsp&mid=WC0b01ac058067c852
Food/lifestyle interactions
Major food/lifestyle interactions
Major:
midostaurin Food/Lifestyle
Applies to: midostaurin
Generally avoid
Grapefruit juice may significantly increase the plasma concentrations of midostaurin. The proposed mechanism is inhibition of CYP450 3A4-mediated first-pass metabolism in the gut wall by certain compounds present in grapefruit. In general, the effect of grapefruit juice is concentration-, dose- and preparation-dependent, and can vary widely among brands. Certain preparations of grapefruit juice (e.g., high dose, double strength) have sometimes demonstrated potent inhibition of CYP450 3A4, while other preparations (e.g., low dose, single strength) have typically demonstrated moderate inhibition. Ketoconazole, a potent CYP450 3A4 inhibitor, has been shown to increase midostaurin systemic exposure (AUC) by greater than 10-fold in healthy volunteers. Increased exposure to midostaurin may increase the risk of adverse effects such as nausea, vomiting, diarrhea, edema, hyperglycemia, hyperuricemia, QT prolongation, neutropenia, lymphopenia, thrombocytopenia, and anemia.
Adjust dosing interval
Food enhances the oral bioavailability of midostaurin. Relative to fasting conditions, midostaurin systemic exposure (AUC) increased by approximately 1.2-fold when administered with a standard meal (457 calories; 50 g fat, 21 g proteins, 18 g carbohydrates) and 1.6-fold when administered with a high-fat meal (1007 calories; 66 g fat, 32 g proteins, 64 g carbohydrates), while midostaurin peak plasma concentration (Cmax ) decreased by 20% and 27%, respectively.
Management
The manufacturer recommends taking midostaurin with food. Midostaurin was administered with food in clinical trials. Patients should avoid consumption of grapefruit and grapefruit juice during treatment with midostaurin.
References (1)
- (2017) "Product Information. Rydapt (midostaurin)." Novartis Pharmaceuticals
Disease interactions
12 potential interactions Applies to: 10 conditions, including Dementia, Urinary Retention, Liver Disease, Long QT Syndrome, and Interstitial Lung Disease.
Central Nervous System Disorders
Moderate:
VESIcare
The solifenacin in VESIcare has a moderate potential interaction with Central Nervous System Disorders.
Solifenacin is associated with anticholinergic central nervous system (CNS) effects. Patients should be monitored for signs of anticholinergic CNS effects, particularly after beginning treatment or increasing the dose. If a patient experiences anticholinergic CNS effects, dose reduction or drug discontinuation should be considered. Solifenacin 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.
Dementia
Moderate:
VESIcare
The solifenacin in VESIcare has a moderate potential interaction with Dementia.
Solifenacin is associated with anticholinergic central nervous system (CNS) effects. Patients should be monitored for signs of anticholinergic CNS effects, particularly after beginning treatment or increasing the dose. If a patient experiences anticholinergic CNS effects, dose reduction or drug discontinuation should be considered. Solifenacin 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.
Gastrointestinal Obstruction
Major:
VESIcare
The solifenacin in VESIcare has a major potential interaction with Gastrointestinal Obstruction.
The use of solifenacin is contraindicated in patients with gastric retention. Caution is advised even when using this agent in patients with decreased gastrointestinal motility.
Glaucoma, Narrow Angle
Major:
VESIcare
The solifenacin in VESIcare has a major potential interaction with Glaucoma, Narrow Angle.
The use of solifenacin is contraindicated in patients with uncontrolled narrow-angle glaucoma. Caution is advised even when using this agent in patients with narrow-angle glaucoma.
Interstitial Lung Disease
Moderate:
midostaurin
Midostaurin 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.
Liver Disease
Major:
VESIcare
The solifenacin in VESIcare has a major potential interaction with Liver Disease.
Solifenacin should be used with caution in patients with reduced hepatic function. Increase in half-life and AUC have been demonstrated in patients with reduce hepatic impairment. Caution should be taken when prescribing this agent to patients with moderate hepatic impairment and the use of doses greater than 5 mg in these patients is not recommended by the manufacturer. Solifenacin is not recommended in patients with severe hepatic impairment. .
Moderate:
midostaurin
Midostaurin has a moderate potential interaction with Liver Disease.
Midostaurin and quizartinib should be used with caution in patients with severe hepatic or severe renal dysfunction as the pharmacokinetics of these agents have not been studied in these patients. No dosage adjustments are recommended in patients with mild or moderate hepatic or renal dysfunction.
Long QT Syndrome
Moderate:
VESIcare
The solifenacin in VESIcare has a moderate potential interaction with Long QT Syndrome.
Dose dependent prolongation in QT interval has been observed with the use of solifenacin. This drug should be used with caution in patients with a known history of QT prolongation or patients who are taking medications known to prolong the QT interval.
Pulmonary Impairment
Moderate:
midostaurin
Midostaurin 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.
Renal Dysfunction
Major:
VESIcare
The solifenacin in VESIcare has a major potential interaction with Renal Dysfunction.
Solifenacin should be used with caution in patients with renal impairment. Increase in half-life and AUC have been demonstrated in patients with severe renal impairment. Caution should be taken when prescribing this agent to patients with renal impairment. Doses greater than 5 mg in patients with severe renal impairment is not recommended by the manufacturer.
Moderate:
midostaurin
Midostaurin has a moderate potential interaction with Renal Dysfunction.
Midostaurin and quizartinib should be used with caution in patients with severe hepatic or severe renal dysfunction as the pharmacokinetics of these agents have not been studied in these patients. No dosage adjustments are recommended in patients with mild or moderate hepatic or renal dysfunction.
Urinary Retention
Major:
VESIcare
The solifenacin in VESIcare has a major potential interaction with Urinary Retention.
The use of solifenacin is contraindicated in patients with urinary retention. Caution is advised even when using this agent in patients with clinically significant bladder outflow obstruction.
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More resources
midostaurin
A total of 699 drugs are known to interact with midostaurin.
- Midostaurin is in the drug class multikinase inhibitors.
- Midostaurin is used to treat the following conditions:
VESIcare
A total of 530 drugs are known to interact with VESIcare.
- Vesicare is in the drug class urinary antispasmodics.
- Vesicare is used to treat the following conditions:
Drug Interaction Classification
| Highly clinically significant. Avoid combinations; the risk of the interaction outweighs the benefit. | |
| Moderately clinically significant. Usually avoid combinations; use it only under special circumstances. | |
| Minimally clinically significant. Minimize risk; assess risk and consider an alternative drug, take steps to circumvent the interaction risk and/or institute a monitoring plan. | |
| No interaction information available. |
Further information
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