Vorinostat is a histone deacetylase (HDAC) inhibitor. It is indicated for the treatment of cutaneous manifestations in patients with cutaneous T-cell lymphoma who have progressive, persistent or recurrent disease on or following 2 systemic therapies. Pulmonary embolism (PE) and deep vein thrombosis (DVT) have been reported with vorinostat therapy; monitor patients for signs and symptoms of PE/DVT.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Hazardous Drugs Classification
-NIOSH 2016 List: Group 1
-NIOSH (Draft) 2020 List: Table 1
-Observe and exercise appropriate precautions for handling, preparation, administration, and disposal of hazardous drugs.
-Use gloves to handle. Cutting, crushing, or otherwise manipulating tablets/capsules will increase exposure.
Emetic Risk
-Minimal/Low
-Administer prn antiemetics as necessary.
Route-Specific Administration
Oral Administration
-Administer vorinostat orally with food.
-Swallow whole. Do not open or crush the capsules.
-Patients should maintain adequate hydration during treatment. Instruct patient to drink at least 2 L/day (roughly eight 8 oz glasses) of fluids.
-Avoid direct contact of powder within capsule with skin or mucous membranes.
Adequately control pre-existing nausea, vomiting, and diarrhea before beginning vorinostat. Among 86 vorinostat recipients, 52.3% had grade 1 or 2 diarrhea, 37.2% had grade 1 or 2 nausea, and 3.5% had grade 3-5 nausea. Grade 1 or 2 vomiting was noted in 13.9%, and 1.2% had grade 3-5 vomiting. Antiemetic and/or anti-diarrheal therapy may be required to manage vorinostat-induced effects. If a patient is intolerant to therapy, dose reduction or drug discontinuation may be needed (see Dosage). Of the 86 patients, 10.5% required a dose modification of vorinostat due to adverse events such as decreased appetite, hypokalemia, nausea, and vomiting. Dehydration may result from severe nausea and vomiting or diarrhea. Replace fluid and electrolytes to prevent dehydration. During clinical trials, it was recommended that patients drink at least 2 L/day to maintain hydration. Also, correct hypokalemia or hypomagnesemia before vorinostat receipt. Carefully monitor electrolytes including potassium, magnesium and calcium every 2 weeks during the first 2 months of therapy and monthly thereafter. Further, consider monitoring potassium and magnesium in symptomatic patients such as those with nausea, vomiting, diarrhea, fluid imbalance, or cardiac symptoms. Other grade 1 or 2 gastrointestinal adverse reactions reported during clinical trials of vorinostat include dysgeusia (27.9%), xerosis (dry mouth) (16.3%), and constipation (15.1%). Grade 1 or 2 weight loss was noted in 19.7% of patients, and grade 3-5 weight loss was noted in 1.2% of patients. Grade 1 or 2 anorexia was noted in 14-22.1% of patients, and grade 3-5 anorexia was noted in 1.2-2.3% of patients. Grade 1 or 2 muscle cramps (spasms) were noted in 17.5% of patients, and grade 3-5 muscle spasms were noted in 2.3% of patients. A single event of cholecystitis was reported.
Among 86 vorinostat recipients for CTCL, 48.8% had grade 1 or 2 fatigue, 3.5% had grade 3-5 fatigue, 13.9% had grade 1 or 2 dizziness, and 1.2% had grade 3-5 dizziness. Grade 1 or 2 headache was noted in 11.6% of patients. Asthenia has been noted, and single events of spinal cord injury and syncope were reported. Further, a single event of Guillain-Barre syndrome was noted among patients without CTCL who received vorinostat. If a patient is intolerant to vorinostat, dose reduction or drug discontinuation may be needed (see Dosage). Vorinostat was discontinued in 9.3% of patients for various adverse events regardless of causality including spinal cord injury and lethargy.
Vorinostat may cause hyperglycemia. Carefully monitor blood glucose every 2 weeks during the first 2 months of vorinostat receipt and monthly thereafter. Adjustment of diet and/or therapy for increased glucose may be necessary for patients with diabetes or prediabetes. Increased serum glucose was reported as an adverse event in 8.1% of 86 patients with CTCL who received 400 mg once daily of vorinostat. Of the 86 patients, 4.6% had a grade 3 severity laboratory abnormality report of increased serum glucose. The abnormality of any severity was noted in 59 of the 86 patients.
Vorinostat can cause dose-related thrombocytopenia and anemia. Of the 86 vorinostat recipients, 19.8% had grade 1 or 2 thrombocytopenia, and 5.8% had grade 3-5 thrombocytopenia. Grade 1 or 2 anemia was noted in 11.7% of patients whereas 2.3% had grade 3-5 anemia. Carefully monitor blood cell counts every 2 weeks during the first 2 months of therapy and monthly thereafter. If platelet counts and/or hemoglobin fall during vorinostat receipt, modify the dose or discontinue vorinostat (see Dosage). Of the 86 patients who received a 400 mg daily dose for CTCL, 10.5% required a dose modification of vorinostat due to adverse events such as thrombocytopenia. The frequencies of more severe thrombocytopenia and anemia were increased with vorinostat doses > 400 mg/day. Also, severe thrombocytopenia and GI bleeding have been reported with concomitant use of vorinostat and other HDAC inhibitors such as valproic acid. Single events of tumor hemorrhage and hemoptysis were reported among patients without CTCL who received vorinostat.
QT prolongation has been reported in patients treated with vorinostat during clinical trials. Three of 86 patients (3.4%) treated with 400 mg/day had Grade 1 (> 450-470 msec) or Grade 2 (471-500 msec or increase of > 60 seconds above baseline) QTc prolongation. In a retrospective analysis of three phase I and two phase II trials, 116 patients had a baseline and at least 1 follow-up ECG. Four (3.4%) patients had Grade 2 and 1 patient (0.8%) had Grade 3 (> 500 msec) QTc prolongation. In 49 non-cutaneous T-cell lymphoma patients from 3 clinical trials who had complete evaluation of QT interval, 2 had QTc measurements > 500 msec, and 1 had a QTc prolongation of > 60 sec.
Carefully monitor serum creatinine every 2 weeks during the first 2 months of therapy and monthly thereafter. If a patient is intolerant to vorinostat, dose reduction or drug discontinuation may be needed (see Dosage). Of the 86 patients who received a 400 mg daily dose for CTCL, 10.5% required a dose modification of vorinostat due to adverse events such as increased serum creatinine. In trials, patients were instructed to drink at least 2 L/day of fluids for adequate hydration; dehydration was reported as a serious drug-related adverse event. In the clinical trial, 16.3% had grade 1 or 2 increased creatinine concentrations, and 12.8% had grade 1 or 2 peripheral edema. Transient increases in serum creatinine were detected in 46.5% of the 86 patients. Of these laboratory abnormalities, 34 were NCI CTCAE Grade 1, 5 were Grade 2, and 1 was Grade 3. Single events of pelvi-ureteric obstruction and ureteric obstruction were noted. Vorinostat was discontinued in 9.3% of patients for various adverse events regardless of causality including increased serum creatinine. Among patients without CTCL who did not receive vorinostat, single events of renal failure (unspecified), hyponatremia, and urinary retention were reported. Proteinuria was detected as a lab abnormality in 51.4% of 74 patients. The clinical significance of this finding is unknown.
Vorinostat may cause thromboembolism; be alert for signs and symptoms of events such as pulmonary embolism and deep vein thrombosis, especially in patients with a history of thromboembolic events. Of 86 patients with cutaneous T-cell lymphoma (CTCL), 4.7% had pulmonary embolism. Single events of deep venous thrombosis, myocardial infarction, and ischemic stroke were also reported. Vorinostat was discontinued in 9.3% of patients for various adverse events regardless of causality including ischemic stroke, chest pain (unspecified), deep vein thrombosis, and pulmonary embolism. Among patients without CTCL who received vorinostat, single events of blurred vision and vasculitis were reported.
If a patient is intolerant to vorinostat, dose reduction or drug discontinuation may be needed (see Dosage). Of 86 patients who received a 400 mg daily dose for CTCL, 10.5% required a dose modification of vorinostat due to adverse events such as leukopenia and neutropenia. Vorinostat may cause a new primary malignancy or infection. Among the 86 vorinostat recipients, 3.5% had squamous cell carcinoma, 10.5% had grade 1 or 2 cough, 15.1% had grade 1 or 2 chills, 1.2% had grade 3 to 5 chills, 10.5% had grade 1 or 2 upper respiratory infection, 9.3% had grade 1 or 2 fever, and 1.2% had grade 3 to 5 fever. Single events of enterococcal infection, infection, lobar pneumonia, sepsis, streptococcal bacteremia, and T-cell lymphoma were noted.
A single event of hypertension was noted among patients without CTCL who received vorinostat.
Of 86 patients who received vorinostat for CTCL, 10.4% had grade 1 or 2 pruritus, and 1.2% had grade 3-5 pruritus. A single event of exfoliative dermatitis was noted. Vorinostat was discontinued in 9.3% of patients for various adverse events regardless of causality including exfoliative dermatitis and angioneurotic edema (angioedema).
Among 86 vorinostat recipients for CTCL, 18.6% had alopecia.
Impaired wound healing has been reported in patients recovering from bowel surgery who received vorinostat perioperatively. Anastomotic healing complications included gastrointestinal fistula, GI perforation, and abscess formation.
Vorinostat is predominantly metabolized by the liver; therefore, use vorinostat with caution in patients with hepatic disease or impairment. Reduce the initial starting dose in patients with mild or moderate hepatic impairment; patients with severe hepatic impairment have not been treated with vorinostat doses exceeding 200 mg/day.
Thrombocytopenia and anemia have been reported with vorinostat therapy. Monitor complete blood counts, including platelet count, every 2 weeks during the first 2 months and monthly thereafter, or as clinically indicated. Dosage reduction or therapy discontinuation may be necessary in patients who develop hematologic toxicity.
Thromboembolic disease including pulmonary embolism (PE) and deep vein thrombosis has been reported during vorinostat therapy; monitor patients closely for any signs or symptoms of PE or DVT.
Pre-existing nausea/vomiting and diarrhea should be controlled prior to initiating vorinostat therapy; patients may require the use of antiemetic and antidiarrheal medication. Fluids and electrolytes should be replaced to prevent dehydration. Instruct patients to drink at least 2 L/day of fluids for adequate hydration during vorinostat therapy.
Patients with diabetes mellitus or glucose intolerance should be monitored closely during vorinostat therapy due to reports of hyperglycemia during treatment. Adjustment of diet and/or therapy for glucose control may be necessary. Monitor blood glucose every 2 weeks during the first 2 months and monthly thereafter, or as clinically indicated.
QT prolongation has been reported with vorinostat therapy. Correct any electrolyte imbalance (i.e., hypomagnesemia, hypokalemia, hypocalcemia) prior to initiating vorinostat therapy. Monitor serum electrolytes (e.g., magnesium, calcium, potassium) every 2 weeks during the first 2 months of therapy and then monthly thereafter; monitor potassium and magnesium more frequently in patients who may be dehydrated (e.g., symptoms of nausea, vomiting, and/or diarrhea, or fluid imbalance) or who have cardiac symptoms. Use vorinostat with caution in patients with conditions that may increase the risk of QT prolongation including congenital long QT syndrome, bradycardia, AV block, heart failure, stress-related cardiomyopathy, myocardial infarction, stroke, or in patients receiving medications known to prolong the QT interval or cause electrolyte imbalances. Females, geriatric patients, patients with sleep deprivation, pheochromocytoma, sickle cell disease, hypothyroidism, hyperparathyroidism, hypothermia, systemic inflammation (e.g., human immunodeficiency virus (HIV) infection, fever, and some autoimmune diseases including rheumatoid arthritis, systemic lupus erythematosus (SLE), and celiac disease) and patients undergoing apheresis procedures (e.g., plasmapheresis [plasma exchange], cytapheresis) may also be at increased risk for QT prolongation.
Avoid accidental exposure to the skin or mucous membranes from crushed or broken vorinostat capsules.
Monitor serum creatinine concentrations every 2 weeks during the first 2 months of therapy and then monthly thereafter. Vorinostat has not been studied in patients with renal impairment.
Vorinostat may cause fetal harm when administered during pregnancy, based on its mechanism of action and data from animal studies. Females of reproductive potential should avoid becoming pregnant while taking vorinostat. Discuss the potential hazard to the fetus if a patient becomes pregnant while taking this drug. Fetal toxicity occurred when pregnant rats or rabbits received a vorinostat dose resulting in approximately 0.5-times the exposure that was observed in humans who received the recommended dose. In animal studies, vorinostat crossed the placenta and was found in fetal plasma at levels up to 50% of maternal concentrations. Fetal toxicity in rats included decreased mean live fetal weights; incomplete ossifications of the skull, thoracic vertebra, and sternebra; and skeletal variations (e.g., cervical ribs, supernumerary ribs, vertebral count, and sacral arch variations). Reductions in mean live fetal weight and an elevated incidence of incomplete ossification of the metacarpals were observed in rabbits.
Counsel patients about the reproductive risk and contraception requirements during vorinostat treatment. Pregnancy testing should be performed in women of reproductive potential within 7 days prior to initiating therapy. These women should use effective contraception during therapy and for at least 6 months after the final vorinostat dose. Due to the risk of male-mediated teratogenicity, male patients should use effective contraception to avoid potential drug exposure in female partners of reproductive potential during therapy and for at least 3 months after the final vorinostat dose. Female patients may be at risk of infertility following vorinostat therapy, based on data from animal studies.
It is not known if vorinostat or its metabolites are secreted in human milk or if it has effects on the breast-fed infant or on milk production. Because there is a potential for adverse reactions in nursing infants from vorinostat, women should be advised against breast-feeding during vorinostat therapy and for at least 1 week after the last dose.
For the treatment of cutaneous T-cell lymphoma (CTCL) in patients who have progressive, persistent, or recurrent disease on or following 2 systemic therapies:
Oral dosage:
Adults: 400 mg orally once daily with food until progressive disease or unacceptable toxicity. If therapy intolerance occurs, reduce the dose to 300 mg orally once daily; if intolerance continues, reduce the dose to 300 mg daily on 5 consecutive days a week. The overall response rate (ORR) was 29.7% following treatment with vorinostat in patients with stage IB to IVB cutaneous T-cell lymphoma (CTCL) consisting of mycosis fungoides and Sezary syndrome who had 2 or more systemic therapy failures in a multicenter, single-arm, phase IIb trial (n = 74). The median number of prior systemic therapies was 3 (range, 1 to 12 therapies); 95.9% of patients had previously received bexarotene. The ORR was defined as a complete or partial response based on an evaluation of skin disease using a modified version of the Severity Weighted Assessment Tool (mSWAT) and an evaluation of lymph node size and blood tumor burden. Progressive disease (PD) was defined as a 25% or greater increase in mSWAT score from baseline or a 50% or greater increase in lymph node size compared to baseline. The median duration of vorinostat treatment was 115.5 days (range, 2 to 480+ days). In patients with stage IIB or higher CTCL (n = 61), the ORR (primary end point) was 29.5% (95% CI, 18.5% to 42.6%). In these patients, the median time to response was 56 days (range, 28 to 171 days), the median duration of response was not reached but estimated to be 185 days (range, 34 to 441+ days), and the median time to progression was not reached but estimated to be 299 days (range, 85 to 470+ days). Pruritus was evaluated using a 10-point visual analog scale (VAS; zero points = no pruritus; 10 points = worst imaginable pruritus). In patients with a baseline VAS score of 3 or greater (n = 65), 32.3% had pruritus relief defined as a VAS score reduction of 3 or greater points or complete resolution of pruritus symptoms for at least 4 continuous weeks. Additionally, pruritus relief was experienced by 43.3% of patients who had a baseline VAS score of 7 to 10 (n = 30).
For the treatment of relapsed or refractory multiple myeloma*, in combination with bortezomib:
Oral dosage:
Adults: 400 mg orally once daily with food on days 1 to 14 in combination with bortezomib 1.3 mg/m2 IV push on days 1, 4, 8, and 11 repeated every 21 days was evaluated in relapsed or refractory multiple myeloma patients in a randomized, double-blind, placebo-controlled, phase III trial (n = 637; VANTAGE 088 trial); 23.7% of patients received concurrent corticosteroids during the study period.
Maximum Dosage Limits:
-Adults
400 mg/day PO.
-Elderly
400 mg/day PO.
-Adolescents
Safety and efficacy have not been established.
-Children
Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
Baseline mild or moderate impairment (bilirubin level 1- to 3-times the upper limit of normal (ULN) or AST level greater than the ULN): Initial dose, 300 mg PO daily with food.
Baseline severe impairment (bilirubin level greater than 3-times the ULN): No manufacturer dosing recommendation provided; patients with severe hepatic impairment have not been treated with vorinostat doses exceeding 200 mg/day.
Patients with Renal Impairment Dosing
Specific guidelines for dosage adjustments in renal impairment are not available; it appears that no initial dosage adjustments are needed. Renal excretion does not play a role in the elimination of vorinostat.
*non-FDA-approved indication
Abciximab: (Moderate) Carefully monitor patients for signs and symptoms of bleeding during coadministration of abciximab and vorinostat. Due to the thrombocytopenic effects of vorinostat, an additive risk of bleeding may occur in patients taking platelet inhibitors.
Acetazolamide: (Moderate) Use vorinostat and carbonic anhydrase inhibitors together with caution; the risk of QT prolongation and arrhythmias may be increased if electrolyte abnormalities occur. Carbonic anhydrase inhibitors increase the excretion of some electrolytes including potassium; electrolyte abnormalities such as hypomagnesemia, hypokalemia, or hypocalcemia may increase the risk of QT prolongation with vorinostat. Frequently monitor serum electrolytes if concomitant use of these drugs is necessary.
Adagrasib: (Major) Concomitant use of adagrasib and vorinostat increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Albuterol; Budesonide: (Moderate) Use vorinostat and corticosteroids together with caution; the risk of QT prolongation and arrhythmias may be increased if electrolyte abnormalities occur. Corticosteroids may cause electrolyte imbalances; hypomagnesemia, hypokalemia, or hypocalcemia and may increase the risk of QT prolongation with vorinostat. Frequently monitor serum electrolytes if concomitant use of these drugs is necessary.
Alfuzosin: (Moderate) Use caution when administering alfuzosin with vorinostat due to the potential for QT prolongation. Alfuzosin may prolong the QT interval in a dose-dependent manner. Vorinostat therapy is also associated with a risk of QT prolongation.
Aliskiren; Hydrochlorothiazide, HCTZ: (Moderate) Use vorinostat and thiazide diuretics together with caution; the risk of QT prolongation and arrhythmias may be increased if electrolyte abnormalities occur. Thiazide diuretics may cause electrolyte imbalances including low potassium; hypomagnesemia, hypokalemia, or hypocalcemia may increase the risk of QT prolongation with vorinostat. Frequently monitor serum electrolytes if concomitant use of these drugs is necessary.
Alteplase: (Moderate) Due to the thrombocytopenic effects of vorinostat, an additive risk of bleeding may be seen in patients receiving concomitant thrombolytic agents.
Amiloride; Hydrochlorothiazide, HCTZ: (Moderate) Use vorinostat and thiazide diuretics together with caution; the risk of QT prolongation and arrhythmias may be increased if electrolyte abnormalities occur. Thiazide diuretics may cause electrolyte imbalances including low potassium; hypomagnesemia, hypokalemia, or hypocalcemia may increase the risk of QT prolongation with vorinostat. Frequently monitor serum electrolytes if concomitant use of these drugs is necessary.
Amiodarone: (Major) Concomitant use of amiodarone and vorinostat increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after drug discontinuation.
Amisulpride: (Major) Monitor ECGs for QT prolongation when amisulpride is administered with vorinostat. Amisulpride causes dose- and concentration- dependent QT prolongation. Vorinostat therapy is associated with a risk of QT prolongation.
Amlodipine; Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Use vorinostat and thiazide diuretics together with caution; the risk of QT prolongation and arrhythmias may be increased if electrolyte abnormalities occur. Thiazide diuretics may cause electrolyte imbalances including low potassium; hypomagnesemia, hypokalemia, or hypocalcemia may increase the risk of QT prolongation with vorinostat. Frequently monitor serum electrolytes if concomitant use of these drugs is necessary.
Amoxicillin; Clarithromycin; Omeprazole: (Major) Clarithromycin is associated with an established risk for QT prolongation and torsades de pointes (TdP). Clarithromycin should be used cautiously with other medications which may prolong the QT interval including vorinostat.
Anagrelide: (Major) Do not use anagrelide and vorinostat together. Anagrelide has been associated with torsade de pointes and ventricular tachycardia and vorinostat is associated with a risk of QT prolongation. Additionally, due to the thrombocytopenic effects of vorinostat, an additive risk of bleeding may occur in patients taking platelet inhibitors.
Apomorphine: (Moderate) Exercise caution when administering apomorphine concomitantly with vorinostat since concurrent use may increase the risk of QT prolongation. Vorinostat therapy is associated with a risk of QT prolongation. Dose-related QTc prolongation is associated with therapeutic apomorphine exposure.
Aripiprazole: (Major) Concomitant use of vorinostat and aripiprazole increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Arsenic Trioxide: (Major) If possible, drugs that are known to prolong the QT interval should be discontinued prior to initiating arsenic trioxide therapy. QT prolongation should be expected with the administration of arsenic trioxide. Torsade de pointes (TdP) and complete atrioventricular block have been reported. Vorinostat therapy is associated with a risk of QT prolongation and should be used cautiously with arsenic trioxide.
Artemether; Lumefantrine: (Major) The administration of artemether; lumefantrine is associated with prolongation of the QT interval. Although there are no studies examining the effects of artemether; lumefantrine in patients receiving other QT prolonging drugs, such as vorinostat, coadministration may result in additive QT prolongation and should be avoided. Consider ECG monitoring if vorinostat must be used with or after artemether; lumefantrine treatment.
Asenapine: (Major) Asenapine and vorinostat have been associated with QT prolongation. According to the manufacturer of asenapine, the drug should be avoided in combination with other agents also known to have this effect.
Aspirin, ASA; Dipyridamole: (Moderate) Carefully monitor patients for signs and symptoms of bleeding during coadministration of dipyridamole and vorinostat. Due to the thrombocytopenic effects of vorinostat, an additive risk of bleeding may occur in patients taking platelet inhibitors.
Atenolol; Chlorthalidone: (Moderate) Use vorinostat and thiazide diuretics together with caution; the risk of QT prolongation and arrhythmias may be increased if electrolyte abnormalities occur. Thiazide diuretics may cause electrolyte imbalances including low potassium; hypomagnesemia, hypokalemia, or hypocalcemia may increase the risk of QT prolongation with vorinostat. Frequently monitor serum electrolytes if concomitant use of these drugs is necessary.
Atomoxetine: (Moderate) Concomitant use of atomoxetine and vorinostat may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Azelastine; Fluticasone: (Moderate) Use vorinostat and corticosteroids together with caution; the risk of QT prolongation and arrhythmias may be increased if electrolyte abnormalities occur. Corticosteroids may cause electrolyte imbalances; hypomagnesemia, hypokalemia, or hypocalcemia and may increase the risk of QT prolongation with vorinostat. Frequently monitor serum electrolytes if concomitant use of these drugs is necessary.
Azilsartan; Chlorthalidone: (Moderate) Use vorinostat and thiazide diuretics together with caution; the risk of QT prolongation and arrhythmias may be increased if electrolyte abnormalities occur. Thiazide diuretics may cause electrolyte imbalances including low potassium; hypomagnesemia, hypokalemia, or hypocalcemia may increase the risk of QT prolongation with vorinostat. Frequently monitor serum electrolytes if concomitant use of these drugs is necessary.
Azithromycin: (Major) Concomitant use of vorinostat and azithromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Beclomethasone: (Moderate) Use vorinostat and corticosteroids together with caution; the risk of QT prolongation and arrhythmias may be increased if electrolyte abnormalities occur. Corticosteroids may cause electrolyte imbalances; hypomagnesemia, hypokalemia, or hypocalcemia and may increase the risk of QT prolongation with vorinostat. Frequently monitor serum electrolytes if concomitant use of these drugs is necessary.
Bedaquiline: (Major) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering bedaquiline with vorinostat. Both drugs have been reported to prolong the QT interval. Prior to initiating bedaquiline, obtain serum electrolyte concentrations and a baseline ECG. An ECG should also be performed at least 2, 12, and 24 weeks after starting bedaquiline therapy.
Benazepril; Hydrochlorothiazide, HCTZ: (Moderate) Use vorinostat and thiazide diuretics together with caution; the risk of QT prolongation and arrhythmias may be increased if electrolyte abnormalities occur. Thiazide diuretics may cause electrolyte imbalances including low potassium; hypomagnesemia, hypokalemia, or hypocalcemia may increase the risk of QT prolongation with vorinostat. Frequently monitor serum electrolytes if concomitant use of these drugs is necessary.
Betamethasone: (Moderate) Use vorinostat and corticosteroids together with caution; the risk of QT prolongation and arrhythmias may be increased if electrolyte abnormalities occur. Corticosteroids may cause electrolyte imbalances; hypomagnesemia, hypokalemia, or hypocalcemia and may increase the risk of QT prolongation with vorinostat. Frequently monitor serum electrolytes if concomitant use of these drugs is necessary.
Bismuth Subcitrate Potassium; Metronidazole; Tetracycline: (Moderate) Concomitant use of metronidazole and vorinostat may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Bismuth Subsalicylate; Metronidazole; Tetracycline: (Moderate) Concomitant use of metronidazole and vorinostat may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Bisoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Use vorinostat and thiazide diuretics together with caution; the risk of QT prolongation and arrhythmias may be increased if electrolyte abnormalities occur. Thiazide diuretics may cause electrolyte imbalances including low potassium; hypomagnesemia, hypokalemia, or hypocalcemia may increase the risk of QT prolongation with vorinostat. Frequently monitor serum electrolytes if concomitant use of these drugs is necessary.
Budesonide: (Moderate) Use vorinostat and corticosteroids together with caution; the risk of QT prolongation and arrhythmias may be increased if electrolyte abnormalities occur. Corticosteroids may cause electrolyte imbalances; hypomagnesemia, hypokalemia, or hypocalcemia and may increase the risk of QT prolongation with vorinostat. Frequently monitor serum electrolytes if concomitant use of these drugs is necessary.
Budesonide; Formoterol: (Moderate) Use vorinostat and corticosteroids together with caution; the risk of QT prolongation and arrhythmias may be increased if electrolyte abnormalities occur. Corticosteroids may cause electrolyte imbalances; hypomagnesemia, hypokalemia, or hypocalcemia and may increase the risk of QT prolongation with vorinostat. Frequently monitor serum electrolytes if concomitant use of these drugs is necessary.
Budesonide; Glycopyrrolate; Formoterol: (Moderate) Use vorinostat and corticosteroids together with caution; the risk of QT prolongation and arrhythmias may be increased if electrolyte abnormalities occur. Corticosteroids may cause electrolyte imbalances; hypomagnesemia, hypokalemia, or hypocalcemia and may increase the risk of QT prolongation with vorinostat. Frequently monitor serum electrolytes if concomitant use of these drugs is necessary.
Bumetanide: (Moderate) Use vorinostat and loop diuretics together with caution; the risk of QT prolongation and arrhythmias may be increased if electrolyte abnormalities occur. Loop diuretics may cause electrolyte imbalances including low potassium; hypomagnesemia, hypokalemia, or hypocalcemia may increase the risk of QT prolongation with vorinostat. Frequently monitor serum electrolytes if concomitant use of these drugs is necessary.
Buprenorphine: (Major) Concomitant use of vorinostat and buprenorphine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Buprenorphine; Naloxone: (Major) Concomitant use of vorinostat and buprenorphine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Cabotegravir; Rilpivirine: (Moderate) Caution is advised when administering rilpivirine with vorinostat. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation. Vorinostat therapy is also associated with a risk of QT prolongation.
Candesartan; Hydrochlorothiazide, HCTZ: (Moderate) Use vorinostat and thiazide diuretics together with caution; the risk of QT prolongation and arrhythmias may be increased if electrolyte abnormalities occur. Thiazide diuretics may cause electrolyte imbalances including low potassium; hypomagnesemia, hypokalemia, or hypocalcemia may increase the risk of QT prolongation with vorinostat. Frequently monitor serum electrolytes if concomitant use of these drugs is necessary.
Captopril; Hydrochlorothiazide, HCTZ: (Moderate) Use vorinostat and thiazide diuretics together with caution; the risk of QT prolongation and arrhythmias may be increased if electrolyte abnormalities occur. Thiazide diuretics may cause electrolyte imbalances including low potassium; hypomagnesemia, hypokalemia, or hypocalcemia may increase the risk of QT prolongation with vorinostat. Frequently monitor serum electrolytes if concomitant use of these drugs is necessary.
Carbonic anhydrase inhibitors: (Moderate) Use vorinostat and carbonic anhydrase inhibitors together with caution; the risk of QT prolongation and arrhythmias may be increased if electrolyte abnormalities occur. Carbonic anhydrase inhibitors increase the excretion of some electrolytes including potassium; electrolyte abnormalities such as hypomagnesemia, hypokalemia, or hypocalcemia may increase the risk of QT prolongation with vorinostat. Frequently monitor serum electrolytes if concomitant use of these drugs is necessary.
Ceritinib: (Major) Avoid coadministration of ceritinib with vorinostat if possible due to the risk of QT prolongation. If concomitant use is unavoidable, periodically monitor ECGs and electrolytes; an interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Ceritinib causes concentration-dependent prolongation of the QT interval. Vorinostat is also associated with QT prolongation.
Chloroquine: (Major) Avoid coadministration of chloroquine with vorinostat due to the increased risk of QT prolongation. If use together is necessary, obtain an ECG at baseline to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Chloroquine is associated with an increased risk of QT prolongation and torsade de pointes (TdP); the risk of QT prolongation is increased with higher chloroquine doses. Vorinostat therapy is also associated with a risk of QT prolongation.
Chlorothiazide: (Moderate) Use vorinostat and thiazide diuretics together with caution; the risk of QT prolongation and arrhythmias may be increased if electrolyte abnormalities occur. Thiazide diuretics may cause electrolyte imbalances including low potassium; hypomagnesemia, hypokalemia, or hypocalcemia may increase the risk of QT prolongation with vorinostat. Frequently monitor serum electrolytes if concomitant use of these drugs is necessary.
Chlorpromazine: (Major) Phenothiazines have been associated with a risk of QT prolongation and/or torsade de pointes (TdP). This risk is generally higher at elevated drugs concentrations of phenothiazines. Chlorpromazine is specifically associated with an established risk of QT prolongation and TdP; case reports have included patients receiving therapeutic doses of chlorpromazine. Agents that prolong the QT interval, such as vorinostat, could lead to torsade de pointes when combined with a phenothiazine, and therefore are generally not recommended for combined use.
Chlorthalidone: (Moderate) Use vorinostat and thiazide diuretics together with caution; the risk of QT prolongation and arrhythmias may be increased if electrolyte abnormalities occur. Thiazide diuretics may cause electrolyte imbalances including low potassium; hypomagnesemia, hypokalemia, or hypocalcemia may increase the risk of QT prolongation with vorinostat. Frequently monitor serum electrolytes if concomitant use of these drugs is necessary.
Cholera Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the live cholera vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to cholera bacteria after receiving the vaccine.
Ciclesonide: (Moderate) Use vorinostat and corticosteroids together with caution; the risk of QT prolongation and arrhythmias may be increased if electrolyte abnormalities occur. Corticosteroids may cause electrolyte imbalances; hypomagnesemia, hypokalemia, or hypocalcemia and may increase the risk of QT prolongation with vorinostat. Frequently monitor serum electrolytes if concomitant use of these drugs is necessary.
Cilostazol: (Moderate) Carefully monitor patients for signs and symptoms of bleeding during coadministration of cilostazol and vorinostat. Due to the thrombocytopenic effects of vorinostat, an additive risk of bleeding may occur in patients taking platelet inhibitors. Platelet aggregation returns to normal within 96 hours of discontinuing cilostazol.
Ciprofloxacin: (Moderate) Concomitant use of ciprofloxacin and vorinostat may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Cisapride: (Contraindicated) Vorinostat therapy is associated with a risk of QT prolongation. Because of the potential for torsade de pointes (TdP), use of cisapride with vorinostat is contraindicated.
Citalopram: (Major) Concomitant use of vorinostat and citalopram increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Clarithromycin: (Major) Clarithromycin is associated with an established risk for QT prolongation and torsades de pointes (TdP). Clarithromycin should be used cautiously with other medications which may prolong the QT interval including vorinostat.
Clofazimine: (Moderate) Concomitant use of clofazimine and vorinostat may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Clopidogrel: (Moderate) Carefully monitor patients for signs and symptoms of bleeding during coadministration of clopidogrel and vorinostat. Due to the thrombocytopenic effects of vorinostat, an additive risk of bleeding may occur in patients taking platelet inhibitors.
Clozapine: (Major) It is unclear if concurrent use of other drugs known to cause neutropenia (e.g., antineoplastic agents) increases the risk or severity of clozapine-induced neutropenia. Because there is no strong rationale for avoiding clozapine in patients treated with these drugs, consider increased absolute neutrophil count (ANC) monitoring and consult the treating oncologist. Additionally, clozapine therapy may lead to S-T segment depression and flattening or inversion of T waves. Vorinostat therapy is associated with a risk of QT prolongation. In theory, coadministration could produce clinically significant prolongation of the QTc interval.
Codeine; Phenylephrine; Promethazine: (Moderate) Concomitant use of promethazine and vorinostat may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Codeine; Promethazine: (Moderate) Concomitant use of promethazine and vorinostat may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Corticosteroids: (Moderate) Use vorinostat and corticosteroids together with caution; the risk of QT prolongation and arrhythmias may be increased if electrolyte abnormalities occur. Corticosteroids may cause electrolyte imbalances; hypomagnesemia, hypokalemia, or hypocalcemia and may increase the risk of QT prolongation with vorinostat. Frequently monitor serum electrolytes if concomitant use of these drugs is necessary.
Cortisone: (Moderate) Use vorinostat and corticosteroids together with caution; the risk of QT prolongation and arrhythmias may be increased if electrolyte abnormalities occur. Corticosteroids may cause electrolyte imbalances; hypomagnesemia, hypokalemia, or hypocalcemia and may increase the risk of QT prolongation with vorinostat. Frequently monitor serum electrolytes if concomitant use of these drugs is necessary.
Crizotinib: (Major) Avoid coadministration of crizotinib with vorinostat due to the risk of QT prolongation. If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes. An interruption of therapy, dose reduction, or discontinuation of therapy may be necessary for crizotinib if QT prolongation occurs. Crizotinib has been associated with concentration-dependent QT prolongation. Vorinostat therapy is also associated with a risk of QT prolongation.
Dasatinib: (Moderate) Monitor for evidence of QT prolongation during concurrent use of dasatinib and vorinostat. In vitro studies have shown that dasatinib has the potential to prolong the QT interval. Vorinostat therapy is associated with a risk of QT prolongation.
Deflazacort: (Moderate) Use vorinostat and corticosteroids together with caution; the risk of QT prolongation and arrhythmias may be increased if electrolyte abnormalities occur. Corticosteroids may cause electrolyte imbalances; hypomagnesemia, hypokalemia, or hypocalcemia and may increase the risk of QT prolongation with vorinostat. Frequently monitor serum electrolytes if concomitant use of these drugs is necessary.
Degarelix: (Moderate) Consider whether the benefits of androgen deprivation therapy outweigh the potential risks in patients receiving vorinostat as concurrent use may increase the risk of QT prolongation. Androgen deprivation therapy (i.e., degarelix) may prolong the QT/QTc interval. Vorinostat therapy is associated with a risk of QT prolongation.
Dengue Tetravalent Vaccine, Live: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the dengue virus vaccine. When feasible, administer indicated vaccines at least 2 weeks prior to initiating immunosuppressant medications. If vaccine administration is necessary, consider revaccination following restoration of immune competence. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure after receiving the vaccine.
Desflurane: (Major) Vorinostat and halogenated anesthetics are associated with a risk of QT prolongation and should be used cautiously in combination.
Deutetrabenazine: (Moderate) The risk of QT prolongation may be increased with coadministration of deutetrabenazine and vorinostat. Deutetrabenazine may prolong the QT interval, but the degree of QT prolongation is not clinically significant when deutetrabenazine is administered within the recommended dosage range. Vorinostat therapy is associated with a risk of QT prolongation.
Dexamethasone: (Moderate) Use vorinostat and corticosteroids together with caution; the risk of QT prolongation and arrhythmias may be increased if electrolyte abnormalities occur. Corticosteroids may cause electrolyte imbalances; hypomagnesemia, hypokalemia, or hypocalcemia and may increase the risk of QT prolongation with vorinostat. Frequently monitor serum electrolytes if concomitant use of these drugs is necessary.
Dexmedetomidine: (Moderate) Concomitant use of dexmedetomidine and vorinostat may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Dextromethorphan; Quinidine: (Major) Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). Vorinostat therapy is associated with a risk of QT prolongation and should be used cautiously with quinidine.
Digoxin: (Moderate) Some antineoplastic agents have been reported to decrease the absorption of digoxin tablets due to their adverse effects on the GI mucosa; the effect on digoxin liquid is not known. The reduction in digoxin tablet absorption has resulted in plasma concentrations that are 50% of pretreatment levels and has been clinically significant in some patients. It is prudent to closely monitor patients for loss of clinical efficacy of digoxin while receiving antineoplastic therapy.
Dipyridamole: (Moderate) Carefully monitor patients for signs and symptoms of bleeding during coadministration of dipyridamole and vorinostat. Due to the thrombocytopenic effects of vorinostat, an additive risk of bleeding may occur in patients taking platelet inhibitors.
Disopyramide: (Major) Disopyramide administration is associated with QT prolongation and torsades de pointes (TdP). Vorinostat therapy is associated with a risk of QT prolongation and should be used cautiously with disopyramide.
Dofetilide: (Major) Coadministration of dofetilide and vorinostat is not recommended as concurrent use may increase the risk of QT prolongation. Dofetilide, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Vorinostat therapy is associated with a risk of QT prolongation.
Dolasetron: (Moderate) Administer dolasetron with caution in combination with vorinostat as concurrent use may increase the risk of QT prolongation. Vorinostat therapy is associated with a risk of QT prolongation. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram.
Dolutegravir; Rilpivirine: (Moderate) Caution is advised when administering rilpivirine with vorinostat. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation. Vorinostat therapy is also associated with a risk of QT prolongation.
Donepezil: (Moderate) Use donepezil with caution in combination with vorinostat as concurrent use may increase the risk of QT prolongation. Case reports indicate that QT prolongation and torsade de pointes (TdP) can occur during donepezil therapy. Vorinostat therapy is associated with a risk of QT prolongation.
Donepezil; Memantine: (Moderate) Use donepezil with caution in combination with vorinostat as concurrent use may increase the risk of QT prolongation. Case reports indicate that QT prolongation and torsade de pointes (TdP) can occur during donepezil therapy. Vorinostat therapy is associated with a risk of QT prolongation.
Dronedarone: (Contraindicated) Concurrent use of dronedarone and vorinostat is contraindicated. Vorinostat therapy is associated with a risk of QT prolongation. Dronedarone administration is associated with a dose-related increase in the QTc interval. The increase in QTc is approximately 10 milliseconds at doses of 400 mg twice daily (the FDA-approved dose) and up to 25 milliseconds at doses of 1600 mg twice daily. Although there are no studies examining the effects of dronedarone in patients receiving other QT prolonging drugs, coadministration of such drugs may result in additive QT prolongation.
Droperidol: (Major) Droperidol should be administered with extreme caution to patients receiving other agents that may prolong the QT interval. Droperidol administration is associated with an established risk for QT prolongation and torsades de pointes (TdP). Any drug known to have potential to prolong the QT interval should not be coadministered with droperidol. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with droperidol include vorinostat.
Efavirenz: (Moderate) Consider alternatives to efavirenz when coadministering with vorinostat as concurrent use may increase the risk of QT prolongation. QTc prolongation has been observed with the use of efavirenz. Vorinostat therapy is associated with a risk of QT prolongation.
Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Consider alternatives to efavirenz when coadministering with vorinostat as concurrent use may increase the risk of QT prolongation. QTc prolongation has been observed with the use of efavirenz. Vorinostat therapy is associated with a risk of QT prolongation.
Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Moderate) Consider alternatives to efavirenz when coadministering with vorinostat as concurrent use may increase the risk of QT prolongation. QTc prolongation has been observed with the use of efavirenz. Vorinostat therapy is associated with a risk of QT prolongation.
Eliglustat: (Major) Eliglustat is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. Drugs with a possible risk for QT prolongation and torsade de pointes (TdP) that should be used cautiously and with close monitoring with eliglustat include vorinostat.
Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Moderate) Caution is advised when administering rilpivirine with vorinostat. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation. Vorinostat therapy is also associated with a risk of QT prolongation.
Emtricitabine; Rilpivirine; Tenofovir Disoproxil Fumarate: (Moderate) Caution is advised when administering rilpivirine with vorinostat. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation. Vorinostat therapy is also associated with a risk of QT prolongation.
Enalapril; Hydrochlorothiazide, HCTZ: (Moderate) Use vorinostat and thiazide diuretics together with caution; the risk of QT prolongation and arrhythmias may be increased if electrolyte abnormalities occur. Thiazide diuretics may cause electrolyte imbalances including low potassium; hypomagnesemia, hypokalemia, or hypocalcemia may increase the risk of QT prolongation with vorinostat. Frequently monitor serum electrolytes if concomitant use of these drugs is necessary.
Encorafenib: (Major) Avoid coadministration of encorafenib and vorinostat due to the potential for additive QT prolongation. If concurrent use cannot be avoided, monitor ECGs for QT prolongation and monitor electrolytes; correct hypokalemia and hypomagnesemia prior to treatment. Encorafenib is associated with dose-dependent prolongation of the QT interval. Vorinostat therapy is associated with a risk of QT prolongation.
Entrectinib: (Major) Avoid coadministration of entrectinib with vorinostat due to the risk of QT prolongation. Both entrectinib and vorinostat have been associated with QT prolongation.
Eprosartan; Hydrochlorothiazide, HCTZ: (Moderate) Use vorinostat and thiazide diuretics together with caution; the risk of QT prolongation and arrhythmias may be increased if electrolyte abnormalities occur. Thiazide diuretics may cause electrolyte imbalances including low potassium; hypomagnesemia, hypokalemia, or hypocalcemia may increase the risk of QT prolongation with vorinostat. Frequently monitor serum electrolytes if concomitant use of these drugs is necessary.
Eptifibatide: (Moderate) Carefully monitor patients for signs and symptoms of bleeding during coadministration of eptifibatide and vorinostat. Due to the thrombocytopenic effects of vorinostat, an additive risk of bleeding may occur in patients taking platelet inhibitors.
Eribulin: (Major) Eribulin has been associated with QT prolongation. If eribulin and another drug that prolongs the QT interval, such as vorinostat, must be coadministered, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation.
Erythromycin: (Major) Concomitant use of vorinostat and erythromycin increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Escitalopram: (Moderate) Concomitant use of escitalopram and vorinostat may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Ethacrynic Acid: (Moderate) Use vorinostat and loop diuretics together with caution; the risk of QT prolongation and arrhythmias may be increased if electrolyte abnormalities occur. Loop diuretics may cause electrolyte imbalances including low potassium; hypomagnesemia, hypokalemia, or hypocalcemia may increase the risk of QT prolongation with vorinostat. Frequently monitor serum electrolytes if concomitant use of these drugs is necessary.
Etrasimod: (Moderate) Concomitant use of etrasimod and vorinostat may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. Etrasimod has a limited effect on the QT/QTc interval at therapeutic doses but may cause bradycardia and atrioventricular conduction delays which may increase the risk for TdP in patients with a prolonged QT/QTc interval.
Fexinidazole: (Major) Concomitant use of fexinidazole and vorinostat increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Fingolimod: (Moderate) Exercise caution when administering fingolimod concomitantly with vorinostat as concurrent use may increase the risk of QT prolongation. Fingolimod initiation results in decreased heart rate and may prolong the QT interval. Fingolimod has not been studied in patients treated with drugs that prolong the QT interval, but drugs that prolong the QT interval have been associated with cases of TdP in patients with bradycardia. Vorinostat is associated with a risk of QT prolongation.
Flecainide: (Moderate) Concomitant use of flecainide and vorinostat may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Fluconazole: (Moderate) Concomitant use of fluconacole and vorinostat may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Fludrocortisone: (Moderate) Use vorinostat and corticosteroids together with caution; the risk of QT prolongation and arrhythmias may be increased if electrolyte abnormalities occur. Corticosteroids may cause electrolyte imbalances; hypomagnesemia, hypokalemia, or hypocalcemia and may increase the risk of QT prolongation with vorinostat. Frequently monitor serum electrolytes if concomitant use of these drugs is necessary.
Flunisolide: (Moderate) Use vorinostat and corticosteroids together with caution; the risk of QT prolongation and arrhythmias may be increased if electrolyte abnormalities occur. Corticosteroids may cause electrolyte imbalances; hypomagnesemia, hypokalemia, or hypocalcemia and may increase the risk of QT prolongation with vorinostat. Frequently monitor serum electrolytes if concomitant use of these drugs is necessary.
Fluoxetine: (Moderate) Concomitant use of fluoxetine and vorinostat may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Fluphenazine: (Minor) Vorinostat therapy is associated with a risk of QT prolongation. Drugs with a possible risk for QT prolongation that should be used cautiously with vorinostat include fluphenazine. Theoretically, fluphenazine may increase the risk of QT prolongation if coadministered with other drugs with a possible risk for QT prolongation.
Fluticasone: (Moderate) Use vorinostat and corticosteroids together with caution; the risk of QT prolongation and arrhythmias may be increased if electrolyte abnormalities occur. Corticosteroids may cause electrolyte imbalances; hypomagnesemia, hypokalemia, or hypocalcemia and may increase the risk of QT prolongation with vorinostat. Frequently monitor serum electrolytes if concomitant use of these drugs is necessary.
Fluticasone; Salmeterol: (Moderate) Use vorinostat and corticosteroids together with caution; the risk of QT prolongation and arrhythmias may be increased if electrolyte abnormalities occur. Corticosteroids may cause electrolyte imbalances; hypomagnesemia, hypokalemia, or hypocalcemia and may increase the risk of QT prolongation with vorinostat. Frequently monitor serum electrolytes if concomitant use of these drugs is necessary.
Fluticasone; Umeclidinium; Vilanterol: (Moderate) Use vorinostat and corticosteroids together with caution; the risk of QT prolongation and arrhythmias may be increased if electrolyte abnormalities occur. Corticosteroids may cause electrolyte imbalances; hypomagnesemia, hypokalemia, or hypocalcemia and may increase the risk of QT prolongation with vorinostat. Frequently monitor serum electrolytes if concomitant use of these drugs is necessary.
Fluticasone; Vilanterol: (Moderate) Use vorinostat and corticosteroids together with caution; the risk of QT prolongation and arrhythmias may be increased if electrolyte abnormalities occur. Corticosteroids may cause electrolyte imbalances; hypomagnesemia, hypokalemia, or hypocalcemia and may increase the risk of QT prolongation with vorinostat. Frequently monitor serum electrolytes if concomitant use of these drugs is necessary.
Fluvoxamine: (Moderate) There may be an increased risk for QT prolongation and torsade de pointes (TdP) during concurrent use of fluvoxamine and vorinostat. Vorinostat therapy is associated with a risk of QT prolongation. Cases of QT prolongation and TdP have been reported during postmarketing use of fluvoxamine.
Formoterol; Mometasone: (Moderate) Use vorinostat and corticosteroids together with caution; the risk of QT prolongation and arrhythmias may be increased if electrolyte abnormalities occur. Corticosteroids may cause electrolyte imbalances; hypomagnesemia, hypokalemia, or hypocalcemia and may increase the risk of QT prolongation with vorinostat. Frequently monitor serum electrolytes if concomitant use of these drugs is necessary.
Foscarnet: (Major) When possible, avoid concurrent use of foscarnet with other drugs known to prolong the QT interval, such as vorinostat. Foscarnet has been associated with postmarketing reports of both QT prolongation and torsade de pointes (TdP). Vorinostat therapy is also associated with a risk of QT prolongation. If these drugs are administered together, obtain an electrocardiogram and electrolyte concentrations before and periodically during treatment.
Fosinopril; Hydrochlorothiazide, HCTZ: (Moderate) Use vorinostat and thiazide diuretics together with caution; the risk of QT prolongation and arrhythmias may be increased if electrolyte abnormalities occur. Thiazide diuretics may cause electrolyte imbalances including low potassium; hypomagnesemia, hypokalemia, or hypocalcemia may increase the risk of QT prolongation with vorinostat. Frequently monitor serum electrolytes if concomitant use of these drugs is necessary.
Fostemsavir: (Moderate) Use vorinostat and fostemsavir together with caution due to the potential for QT prolongation. Vorinostat therapy is associated with a risk of QT prolongation. Supratherapeutic doses of fostemsavir (2,400 mg twice daily, four times the recommended daily dose) have been shown to cause QT prolongation. Fostemsavir causes dose-dependent QT prolongation.
Furosemide: (Moderate) Use vorinostat and loop diuretics together with caution; the risk of QT prolongation and arrhythmias may be increased if electrolyte abnormalities occur. Loop diuretics may cause electrolyte imbalances including low potassium; hypomagnesemia, hypokalemia, or hypocalcemia may increase the risk of QT prolongation with vorinostat. Frequently monitor serum electrolytes if concomitant use of these drugs is necessary.
Gemifloxacin: (Moderate) Due to an increased risk for QT prolongation and torsade de pointes (TdP), caution is advised when administering vorinostat with gemifloxacin. Vorinostat therapy is associated with a risk of QT prolongation. Gemifloxacin may also prolong the QT interval in some patients, with the maximal change in the QTc interval occurring approximately 5 to 10 hours following oral administration. The likelihood of QTc prolongation may increase with increasing dose of gemifloxacin; therefore, the recommended dose should not be exceeded especially in patients with renal or hepatic impairment where the Cmax and AUC are slightly higher.
Gemtuzumab Ozogamicin: (Moderate) Use gemtuzumab ozogamicin and vorinostat together with caution due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If these agents are used together, obtain an ECG and serum electrolytes prior to the start of gemtuzumab and as needed during treatment. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin. Vorinostat therapy is associated with a risk of QT prolongation.
Gilteritinib: (Moderate) Use caution and monitor for additive QT prolongation if concurrent use of gilteritinib and vorinostat is necessary. Both drugs have been associated with QT prolongation.
Glasdegib: (Major) Avoid coadministration of glasdegib with vorinostat due to the potential for additive QT prolongation. If coadministration cannot be avoided, monitor patients for increased risk of QT prolongation with increased frequency of ECG monitoring. Glasdegib therapy may result in QT prolongation and ventricular arrhythmias including ventricular fibrillation and ventricular tachycardia. Vorinostat therapy is also associated with a risk of QT prolongation.
Goserelin: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., goserelin) outweigh the potential risks of QT prolongation in patients receiving vorinostat. Vorinostat therapy is associated with a risk of QT prolongation. Androgen deprivation therapy may also prolong the QT/QTc interval.
Granisetron: (Moderate) Use granisetron with caution in combination with vorinostat due to the risk of QT prolongation. Both granisetron and vorinostat have been associated with QT prolongation.
Halogenated Anesthetics: (Major) Vorinostat and halogenated anesthetics are associated with a risk of QT prolongation and should be used cautiously in combination.
Haloperidol: (Moderate) Caution is advisable when combining haloperidol concurrently with vorinostat as concurrent use may increase the risk of QT prolongation. QT prolongation and torsade de pointes (TdP) have been observed during haloperidol treatment. Excessive doses (particularly in the overdose setting) or IV administration of haloperidol may be associated with a higher risk of QT prolongation. Vorinostat therapy is also associated with a risk of QT prolongation.
Histrelin: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., histrelin) outweigh the potential risks of QT prolongation in patients receiving vorinostat. Vorinostat therapy is associated with a risk of QT prolongation. Androgen deprivation therapy may also prolong the QT/QTc interval.
Hydrochlorothiazide, HCTZ: (Moderate) Use vorinostat and thiazide diuretics together with caution; the risk of QT prolongation and arrhythmias may be increased if electrolyte abnormalities occur. Thiazide diuretics may cause electrolyte imbalances including low potassium; hypomagnesemia, hypokalemia, or hypocalcemia may increase the risk of QT prolongation with vorinostat. Frequently monitor serum electrolytes if concomitant use of these drugs is necessary.
Hydrochlorothiazide, HCTZ; Moexipril: (Moderate) Use vorinostat and thiazide diuretics together with caution; the risk of QT prolongation and arrhythmias may be increased if electrolyte abnormalities occur. Thiazide diuretics may cause electrolyte imbalances including low potassium; hypomagnesemia, hypokalemia, or hypocalcemia may increase the risk of QT prolongation with vorinostat. Frequently monitor serum electrolytes if concomitant use of these drugs is necessary.
Hydrocortisone: (Moderate) Use vorinostat and corticosteroids together with caution; the risk of QT prolongation and arrhythmias may be increased if electrolyte abnormalities occur. Corticosteroids may cause electrolyte imbalances; hypomagnesemia, hypokalemia, or hypocalcemia and may increase the risk of QT prolongation with vorinostat. Frequently monitor serum electrolytes if concomitant use of these drugs is necessary.
Hydroxychloroquine: (Major) Concomitant use of vorinostat and hydroxychloroquine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Hydroxyzine: (Moderate) Concomitant use of hydroxyzine and vorinostat may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Ibutilide: (Major) Vorinostat therapy is associated with a risk of QT prolongation. Ibutilide administration can cause QT prolongation and torsades de pointes (TdP); proarrhythmic events should be anticipated. The potential for proarrhythmic events with ibutilide increases with the coadministration of other drugs that prolong the QT interval. Use caution and close monitoring during concurrent administration.
Iloperidone: (Major) Iloperidone has been associated with QT prolongation; however, torsade de pointes (TdP) has not been reported. According to the manufacturer, since iloperidone may prolong the QT interval, it should be avoided in combination with other agents also known to have this effect, such as vorinostat.
Inotuzumab Ozogamicin: (Major) Avoid coadministration of inotuzumab ozogamicin with vorinostat due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). If coadministration is unavoidable, obtain an ECG and serum electrolytes prior to the start of treatment, after treatment initiation, and periodically during treatment. Both inotuzumab and vorinostat have been associated with QT interval prolongation.
Irbesartan; Hydrochlorothiazide, HCTZ: (Moderate) Use vorinostat and thiazide diuretics together with caution; the risk of QT prolongation and arrhythmias may be increased if electrolyte abnormalities occur. Thiazide diuretics may cause electrolyte imbalances including low potassium; hypomagnesemia, hypokalemia, or hypocalcemia may increase the risk of QT prolongation with vorinostat. Frequently monitor serum electrolytes if concomitant use of these drugs is necessary.
Isoflurane: (Major) Vorinostat and halogenated anesthetics are associated with a risk of QT prolongation and should be used cautiously in combination.
Itraconazole: (Moderate) Use itraconazole with caution in combination with vorinostat as concurrent use may increase the risk of QT prolongation. Itraconazole has been associated with prolongation of the QT interval. Vorinostat therapy is associated with a risk of QT prolongation.
Ivosidenib: (Major) Avoid coadministration of ivosidenib with vorinostat due to an increased risk of QT prolongation. If concomitant use is unavoidable, monitor ECGs for QTc prolongation and monitor electrolytes; correct any electrolyte abnormalities as clinically appropriate. An interruption of therapy and dose reduction of ivosidenib may be necessary if QT prolongation occurs. Prolongation of the QTc interval and ventricular arrhythmias have been reported in patients treated with ivosidenib. Vorinostat has been associated with a risk of QT prolongation.
Ketoconazole: (Contraindicated) Avoid concomitant use of ketoconazole and vorinostat due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
Lansoprazole; Amoxicillin; Clarithromycin: (Major) Clarithromycin is associated with an established risk for QT prolongation and torsades de pointes (TdP). Clarithromycin should be used cautiously with other medications which may prolong the QT interval including vorinostat.
Lapatinib: (Moderate) Monitor for evidence of QT prolongation if lapatinib is administered with vorinostat. Lapatinib has been associated with concentration-dependent QT prolongation; ventricular arrhythmias and torsade de pointes (TdP) have been reported in postmarketing experience with lapatinib. Vorinostat therapy is also associated with a risk of QT prolongation.
Lefamulin: (Major) Avoid coadministration of lefamulin with vorinostat as concurrent use may increase the risk of QT prolongation. If coadministration cannot be avoided, monitor ECG during treatment. Lefamulin has a concentration dependent QTc prolongation effect. The pharmacodynamic interaction potential to prolong the QT interval of the electrocardiogram between lefamulin and other drugs that effect cardiac conduction is unknown. Vorinostat therapy is associated with a risk of QT prolongation.
Lenvatinib: (Major) Avoid coadministration of lenvatinib with vorinostat due to the risk of QT prolongation. Prolongation of the QT interval has been reported with lenvatinib therapy. Vorinostat therapy is also associated with a risk of QT prolongation.
Leuprolide: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving vorinostat. Vorinostat therapy is associated with a risk of QT prolongation. Androgen deprivation therapy may also prolong the QT/QTc interval.
Leuprolide; Norethindrone: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving vorinostat. Vorinostat therapy is associated with a risk of QT prolongation. Androgen deprivation therapy may also prolong the QT/QTc interval.
Levofloxacin: (Moderate) Concomitant use of levofloxacin and vorinostat may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Levoketoconazole: (Contraindicated) Avoid concomitant use of ketoconazole and vorinostat due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
Lisinopril; Hydrochlorothiazide, HCTZ: (Moderate) Use vorinostat and thiazide diuretics together with caution; the risk of QT prolongation and arrhythmias may be increased if electrolyte abnormalities occur. Thiazide diuretics may cause electrolyte imbalances including low potassium; hypomagnesemia, hypokalemia, or hypocalcemia may increase the risk of QT prolongation with vorinostat. Frequently monitor serum electrolytes if concomitant use of these drugs is necessary.
Lithium: (Moderate) Concomitant use of lithium and vorinostat may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Lofexidine: (Major) ECG monitoring is recommended if lofexidine is coadministered with vorinostat due to the potential for additive QT prolongation. Lofexidine prolongs the QT interval. Vorinostat therapy is associated with a risk of QT prolongation.
Loop diuretics: (Moderate) Use vorinostat and loop diuretics together with caution; the risk of QT prolongation and arrhythmias may be increased if electrolyte abnormalities occur. Loop diuretics may cause electrolyte imbalances including low potassium; hypomagnesemia, hypokalemia, or hypocalcemia may increase the risk of QT prolongation with vorinostat. Frequently monitor serum electrolytes if concomitant use of these drugs is necessary.
Loperamide: (Moderate) Loperamide should be used cautiously and with close monitoring with vorinostat. Vorinostat therapy is associated with a risk of QT prolongation and high doses of loperamide have been associated with serious cardiac toxicities, including syncope, ventricular tachycardia, QT prolongation, torsade de pointes (TdP), and cardiac arrest. Coadministration may further increase the risk for QT prolongation and TdP.
Loperamide; Simethicone: (Moderate) Loperamide should be used cautiously and with close monitoring with vorinostat. Vorinostat therapy is associated with a risk of QT prolongation and high doses of loperamide have been associated with serious cardiac toxicities, including syncope, ventricular tachycardia, QT prolongation, torsade de pointes (TdP), and cardiac arrest. Coadministration may further increase the risk for QT prolongation and TdP.
Lopinavir; Ritonavir: (Major) Avoid coadministration of lopinavir with vorinostat due to the potential for additive QT prolongation. If use together is necessary, obtain a baseline ECG to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Both drugs are associated with QT prolongation. (Major) The use of ritonavir could result in QT prolongation. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with ritonavir include vorinostat.
Losartan; Hydrochlorothiazide, HCTZ: (Moderate) Use vorinostat and thiazide diuretics together with caution; the risk of QT prolongation and arrhythmias may be increased if electrolyte abnormalities occur. Thiazide diuretics may cause electrolyte imbalances including low potassium; hypomagnesemia, hypokalemia, or hypocalcemia may increase the risk of QT prolongation with vorinostat. Frequently monitor serum electrolytes if concomitant use of these drugs is necessary.
Macimorelin: (Major) Avoid concurrent administration of macimorelin with drugs that prolong the QT interval, such as vorinostat. Use of these drugs together may increase the risk of developing torsade de pointes-type ventricular tachycardia. Sufficient washout time of drugs that are known to prolong the QT interval prior to administration of macimorelin is recommended. Treatment with macimorelin has been associated with an increase in the corrected QT (QTc) interval. Vorinostat therapy is associated with a risk of QT prolongation.
Maprotiline: (Major) Maprotiline has been reported to prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations). Cases of long QT syndrome and torsade de pointes (TdP) tachycardia have been described with maprotiline use, but rarely occur when the drug is used alone in normal prescribed doses and in the absence of other known risk factors for QT prolongation. Limited data are available regarding the safety of maprotiline in combination with other QT-prolonging drugs. Vorinostat therapy is associated with a risk of QT prolongation and should be used cautiously with maprotiline.
Mefloquine: (Moderate) Mefloquine should be used with caution in patients receiving vorinostat as concurrent use may increase the risk of QT prolongation. There is evidence that the use of halofantrine after mefloquine causes a significant lengthening of the QTc interval. Mefloquine alone has not been reported to cause QT prolongation. Vorinostat therapy is associated with a risk of QT prolongation.
Methadone: (Major) The need to coadminister methadone with drugs known to prolong the QT interval should be done with extreme caution and a careful assessment of treatment risks versus benefits. Methadone is considered to be associated with an increased risk for QT prolongation and torsades de pointes (TdP), especially at higher doses (> 200 mg/day but averaging approximately 400 mg/day in adult patients). Laboratory studies, both in vivo and in vitro, have demonstrated that methadone inhibits cardiac potassium channels and prolongs the QT interval. Most cases involve patients being treated for pain with large, multiple daily doses of methadone, although cases have been reported in patients receiving doses commonly used for maintenance treatment of opioid addiction. Vorinostat therapy is associated with a risk of QT prolongation and should be used cautiously with methadone.
Methazolamide: (Moderate) Use vorinostat and carbonic anhydrase inhibitors together with caution; the risk of QT prolongation and arrhythmias may be increased if electrolyte abnormalities occur. Carbonic anhydrase inhibitors increase the excretion of some electrolytes including potassium; electrolyte abnormalities such as hypomagnesemia, hypokalemia, or hypocalcemia may increase the risk of QT prolongation with vorinostat. Frequently monitor serum electrolytes if concomitant use of these drugs is necessary.
Methylprednisolone: (Moderate) Use vorinostat and corticosteroids together with caution; the risk of QT prolongation and arrhythmias may be increased if electrolyte abnormalities occur. Corticosteroids may cause electrolyte imbalances; hypomagnesemia, hypokalemia, or hypocalcemia and may increase the risk of QT prolongation with vorinostat. Frequently monitor serum electrolytes if concomitant use of these drugs is necessary.
Metolazone: (Moderate) Use vorinostat and thiazide diuretics together with caution; the risk of QT prolongation and arrhythmias may be increased if electrolyte abnormalities occur. Thiazide diuretics may cause electrolyte imbalances including low potassium; hypomagnesemia, hypokalemia, or hypocalcemia may increase the risk of QT prolongation with vorinostat. Frequently monitor serum electrolytes if concomitant use of these drugs is necessary.
Metoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Use vorinostat and thiazide diuretics together with caution; the risk of QT prolongation and arrhythmias may be increased if electrolyte abnormalities occur. Thiazide diuretics may cause electrolyte imbalances including low potassium; hypomagnesemia, hypokalemia, or hypocalcemia may increase the risk of QT prolongation with vorinostat. Frequently monitor serum electrolytes if concomitant use of these drugs is necessary.
Metronidazole: (Moderate) Concomitant use of metronidazole and vorinostat may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Midostaurin: (Major) The concomitant use of midostaurin and vorinostat may lead to additive QT interval prolongation. If these drugs are used together, consider electrocardiogram monitoring. Correct any electrolyte imbalance prior to starting vorinostat; monitor serum electrolytes during therapy. In clinical trials, QT prolongation has been reported in patients who received midostaurin as single-agent therapy or in combination with cytarabine and daunorubicin. QT prolongation has been reported in patients who received vorinostat in a clinical study and in a retrospective analysis; however, the QTc interval was not prolonged following a single 800-mg vorinostat dose in a randomized, 2-period, crossover study designed to assess the impact of vorinostat on ventricular repolarization in patients with advanced cancer.
Mifepristone: (Moderate) Concomitant use of mifepristone and vorinostat may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Mirtazapine: (Moderate) Concomitant use of mirtazapine and vorinostat may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Mobocertinib: (Major) Concomitant use of mobocertinib and vorinostat increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Mometasone: (Moderate) Use vorinostat and corticosteroids together with caution; the risk of QT prolongation and arrhythmias may be increased if electrolyte abnormalities occur. Corticosteroids may cause electrolyte imbalances; hypomagnesemia, hypokalemia, or hypocalcemia and may increase the risk of QT prolongation with vorinostat. Frequently monitor serum electrolytes if concomitant use of these drugs is necessary.
Moxifloxacin: (Major) Concurrent use of vorinostat and moxifloxacin should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Vorinostat therapy is associated with a risk of QT prolongation. Moxifloxacin has also been associated with prolongation of the QT interval. Additionally, post-marketing surveillance has identified very rare cases of ventricular arrhythmias including TdP, usually in patients with severe underlying proarrhythmic conditions. The likelihood of QT prolongation may increase with increasing concentrations of moxifloxacin, therefore the recommended dose or infusion rate should not be exceeded.
Nilotinib: (Major) Avoid the concomitant use of nilotinib and vorinotat; significant prolongation of the QT interval may occur. Sudden death and QT prolongation have been reported in patients who received nilotinib therapy. Vorinostat therapy is associated with a risk of QT prolongation.
Nirmatrelvir; Ritonavir: (Major) The use of ritonavir could result in QT prolongation. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with ritonavir include vorinostat.
Ofloxacin: (Moderate) Concomitant use of ofloxacin and vorinostat may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Olanzapine: (Moderate) Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances. Therefore, caution is advised when administering olanzapine with drugs having an established causal association with QT prolongation and torsade de pointes (TdP). Vorinostat therapy is associated with a risk of QT prolongation and should be used cautiously with olanzapine.
Olanzapine; Fluoxetine: (Moderate) Concomitant use of fluoxetine and vorinostat may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. (Moderate) Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances. Therefore, caution is advised when administering olanzapine with drugs having an established causal association with QT prolongation and torsade de pointes (TdP). Vorinostat therapy is associated with a risk of QT prolongation and should be used cautiously with olanzapine.
Olanzapine; Samidorphan: (Moderate) Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances. Therefore, caution is advised when administering olanzapine with drugs having an established causal association with QT prolongation and torsade de pointes (TdP). Vorinostat therapy is associated with a risk of QT prolongation and should be used cautiously with olanzapine.
Olmesartan; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Use vorinostat and thiazide diuretics together with caution; the risk of QT prolongation and arrhythmias may be increased if electrolyte abnormalities occur. Thiazide diuretics may cause electrolyte imbalances including low potassium; hypomagnesemia, hypokalemia, or hypocalcemia may increase the risk of QT prolongation with vorinostat. Frequently monitor serum electrolytes if concomitant use of these drugs is necessary.
Olmesartan; Hydrochlorothiazide, HCTZ: (Moderate) Use vorinostat and thiazide diuretics together with caution; the risk of QT prolongation and arrhythmias may be increased if electrolyte abnormalities occur. Thiazide diuretics may cause electrolyte imbalances including low potassium; hypomagnesemia, hypokalemia, or hypocalcemia may increase the risk of QT prolongation with vorinostat. Frequently monitor serum electrolytes if concomitant use of these drugs is necessary.
Olopatadine; Mometasone: (Moderate) Use vorinostat and corticosteroids together with caution; the risk of QT prolongation and arrhythmias may be increased if electrolyte abnormalities occur. Corticosteroids may cause electrolyte imbalances; hypomagnesemia, hypokalemia, or hypocalcemia and may increase the risk of QT prolongation with vorinostat. Frequently monitor serum electrolytes if concomitant use of these drugs is necessary.
Ondansetron: (Major) Concomitant use of vorinostat and ondansetron increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary. Do not exceed 16 mg of IV ondansetron in a single dose; the degree of QT prolongation associated with ondansetron significantly increases above this dose.
Osilodrostat: (Moderate) Monitor ECGs in patients receiving osilodrostat with vorinostat. Osilodrostat is associated with dose-dependent QT prolongation. Vorinostat therapy is associated with a risk of QT prolongation.
Osimertinib: (Major) Avoid coadministration of vorinostat with osimertinib if possible due to the risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, periodically monitor ECGs for QT prolongation and monitor electrolytes; an interruption of osimertinib therapy with dose reduction or discontinuation of therapy may be necessary if QT prolongation occurs. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib. Vorinostat therapy is also associated with a risk of QT prolongation.
Oxaliplatin: (Major) Monitor electrolytes and ECGs for QT prolongation if coadministration of vorinostat with oxaliplatin is necessary; correct electrolyte abnormalities prior to administration of oxaliplatin. Vorinostat therapy is associated with a risk of QT prolongation. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have also been reported with oxaliplatin use in postmarketing experience.
Ozanimod: (Major) In general, do not initiate ozanimod in patients taking vorinostat due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. Ozanimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ozanimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Vorinostat therapy is associated with a risk of QT prolongation.
Pacritinib: (Major) Concomitant use of pacritinib and vorinostat increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Paliperidone: (Major) Paliperidone has been associated with QT prolongation; TdP and ventricular fibrillation have been reported in the setting of overdose. According to the manufacturer, since paliperidone may prolong the QT interval, it should be avoided in combination with other agents also known to have this effect. Vorinostat therapy is associated with a risk of QT prolongation. If coadministration is necessary and the patient has known risk factors for cardiac disease or arrhythmias, close monitoring is essential.
Panobinostat: (Major) QT prolongation has been reported with panobinostat therapy in patients with multiple myeloma in a clinical trial; use of panobinostat with other agents that prolong the QT interval is not recommended. Obtain an electrocardiogram at baseline and periodically during treatment. Hold panobinostat if the QTcF increases to >= 480 milliseconds during therapy; permanently discontinue if QT prolongation does not resolve. Drugs with a possible risk for QT prolongation and torsade de pointes that should be used cautiously and with close monitoring with panobinostat include vorinostat.
Pasireotide: (Moderate) Use caution when using pasireotide in combination with vorinostat as concurrent use may increase the risk of QT prolongation. QT prolongation has occurred with pasireotide at therapeutic and supra-therapeutic doses. Vorinostat therapy is associated with a risk of QT prolongation.
Pazopanib: (Major) Coadministration of pazopanib and other drugs that prolong the QT interval, such as vorinostat, is not advised; pazopanib has been reported to prolong the QT interval. If pazopanib and vorinostat must be continued, closely monitor the patient for QT interval prolongation.
Pentamidine: (Major) Vorinostat therapy is associated with a risk of QT prolongation. Vorinostat should be used with caution if given with other agents that may prolong the QT interval including pentamidine.
Perphenazine: (Minor) Vorinostat therapy is associated with a risk of QT prolongation. Drugs with a possible risk for QT prolongation and torsade de pointes (TdP) that should be used cautiously with vorinostat include perphenazine. Theoretically, perphenazine may increase the risk of QT prolongation if coadministered with other drugs with a possible risk for QT prolongation.
Perphenazine; Amitriptyline: (Minor) Vorinostat therapy is associated with a risk of QT prolongation. Drugs with a possible risk for QT prolongation and torsade de pointes (TdP) that should be used cautiously with vorinostat include perphenazine. Theoretically, perphenazine may increase the risk of QT prolongation if coadministered with other drugs with a possible risk for QT prolongation.
Pimavanserin: (Major) Pimavanserin may cause QT prolongation and should generally be avoided in patients receiving other medications known to prolong the QT interval. Vorinostat therapy is also associated with a risk of QT prolongation. Coadministration may increase the risk for QT prolongation.
Pimozide: (Contraindicated) Pimozide is associated with a well-established risk of QT prolongation and torsade de pointes (TdP). Because of the potential for TdP, use of vorinostat with pimozide is contraindicated.
Pitolisant: (Major) Avoid coadministration of pitolisant with vorinostat as concurrent use may increase the risk of QT prolongation. Pitolisant prolongs the QT interval. Vorinostat therapy is also associated with a risk of QT prolongation.
Ponesimod: (Major) In general, do not initiate ponesimod in patients taking vorinostat due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP); additive immunosuppression may also occur which may extend the duration or severity of immune suppression. If treatment initiation is considered, seek advice from a cardiologist and monitor for signs and symptoms of infection. Ponesimod initiation may result in a transient decrease in heart rate and atrioventricular conduction delays. Ponesimod has not been studied in patients taking concurrent QT prolonging drugs; however, QT prolonging drugs have been associated with TdP in patients with bradycardia. Vorinostat therapy is associated with a risk of QT prolongation.
Posaconazole: (Moderate) Use posaconazole with caution in combination with vorinostat as concurrent use may increase the risk of QT prolongation. Posaconazole has been associated with prolongation of the QT interval as well as rare cases of torsade de pointes. Vorinostat therapy is also associated with a risk of QT prolongation.
Prasugrel: (Moderate) Carefully monitor patients for signs and symptoms of bleeding during coadministration of prasugrel and vorinostat. Due to the thrombocytopenic effects of vorinostat, an additive risk of bleeding may occur in patients taking platelet inhibitors.
Prednisolone: (Moderate) Use vorinostat and corticosteroids together with caution; the risk of QT prolongation and arrhythmias may be increased if electrolyte abnormalities occur. Corticosteroids may cause electrolyte imbalances; hypomagnesemia, hypokalemia, or hypocalcemia and may increase the risk of QT prolongation with vorinostat. Frequently monitor serum electrolytes if concomitant use of these drugs is necessary.
Prednisone: (Moderate) Use vorinostat and corticosteroids together with caution; the risk of QT prolongation and arrhythmias may be increased if electrolyte abnormalities occur. Corticosteroids may cause electrolyte imbalances; hypomagnesemia, hypokalemia, or hypocalcemia and may increase the risk of QT prolongation with vorinostat. Frequently monitor serum electrolytes if concomitant use of these drugs is necessary.
Primaquine: (Moderate) Exercise caution when administering primaquine in combination with vorinostat. Primaquine and vorinostat are associated with QT prolongation.
Procainamide: (Major) Procainamide is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Vorinostat therapy is associated with a risk of QT prolongation and should be used cautiously with procainamide.
Prochlorperazine: (Minor) Vorinostat therapy is associated with a risk of QT prolongation. Drugs with a possible risk for QT prolongation that should be used cautiously with vorinostat include prochlorperazine. Theoretically, prochlorperazine may increase the risk of QT prolongation if coadministered with other drugs with a possible risk for QT prolongation.
Promethazine: (Moderate) Concomitant use of promethazine and vorinostat may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Promethazine; Dextromethorphan: (Moderate) Concomitant use of promethazine and vorinostat may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Promethazine; Phenylephrine: (Moderate) Concomitant use of promethazine and vorinostat may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Propafenone: (Major) Concomitant use of vorinostat and propafenone increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Quetiapine: (Major) Concomitant use of vorinostat and quetiapine increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Quinapril; Hydrochlorothiazide, HCTZ: (Moderate) Use vorinostat and thiazide diuretics together with caution; the risk of QT prolongation and arrhythmias may be increased if electrolyte abnormalities occur. Thiazide diuretics may cause electrolyte imbalances including low potassium; hypomagnesemia, hypokalemia, or hypocalcemia may increase the risk of QT prolongation with vorinostat. Frequently monitor serum electrolytes if concomitant use of these drugs is necessary.
Quinidine: (Major) Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). Vorinostat therapy is associated with a risk of QT prolongation and should be used cautiously with quinidine.
Quinine: (Major) Concurrent use of quinine and vorinostat should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Quinine has been associated with prolongation of the QT interval and rare cases of TdP. Vorinostat therapy is also associated with a risk of QT prolongation.
Quizartinib: (Major) Concomitant use of quizartinib and vorinostat increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Ranolazine: (Moderate) Use ranolazine with caution in combination with vorinostat as concurrent use may increase the risk of QT prolongation. Ranolazine is associated with dose- and plasma concentration-related increases in the QTc interval. Although there are no studies examining the effects of ranolazine in patients receiving other QT prolonging drugs, coadministration of such drugs may result in additive QT prolongation. Vorinostat therapy is associated with a risk of QT prolongation.
Relugolix: (Moderate) Consider whether the benefits of androgen deprivation therapy outweigh the potential risks in patients receiving other QT prolonging agents. Androgen deprivation therapy (i.e., relugolix) may prolong the QT/QTc interval. Vorinostat therapy is associated with a risk of QT prolongation.
Relugolix; Estradiol; Norethindrone acetate: (Moderate) Consider whether the benefits of androgen deprivation therapy outweigh the potential risks in patients receiving other QT prolonging agents. Androgen deprivation therapy (i.e., relugolix) may prolong the QT/QTc interval. Vorinostat therapy is associated with a risk of QT prolongation.
Reteplase, r-PA: (Moderate) Due to the thrombocytopenic effects of vorinostat, an additive risk of bleeding may be seen in patients receiving concomitant thrombolytic agents.
Ribociclib: (Major) Avoid coadministration of ribociclib with vorinostat due to an increased risk for QT prolongation. Ribociclib has been shown to prolong the QT interval in a concentration-dependent manner. Vorinostat has also been associated with QT prolongation. Concomitant use may increase the risk for QT prolongation.
Ribociclib; Letrozole: (Major) Avoid coadministration of ribociclib with vorinostat due to an increased risk for QT prolongation. Ribociclib has been shown to prolong the QT interval in a concentration-dependent manner. Vorinostat has also been associated with QT prolongation. Concomitant use may increase the risk for QT prolongation.
Rilpivirine: (Moderate) Caution is advised when administering rilpivirine with vorinostat. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation. Vorinostat therapy is also associated with a risk of QT prolongation.
Risperidone: (Moderate) Use risperidone and vorinostat together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Vorinostat therapy is also associated with a risk of QT prolongation.
Ritonavir: (Major) The use of ritonavir could result in QT prolongation. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with ritonavir include vorinostat.
Romidepsin: (Moderate) Consider monitoring electrolytes and ECGs at baseline and periodically during treatment if romidepsin is administered with vorinostat as concurrent use may increase the risk of QT prolongation. Romidepsin has been reported to prolong the QT interval. Vorinostat therapy is associated with a risk of QT prolongation.
Saquinavir: (Major) Saquinavir boosted with ritonavir increases the QT interval in a dose-dependent fashion, which may increase the risk for serious arrhythmias such as torsade de pointes (TdP). Avoid administering saquinavir boosted with ritonavir concurrently with other drugs that may prolong the QT interval, such as vorinostat. If no acceptable alternative therapy is available, perform a baseline ECG prior to initiation of concomitant therapy and carefully follow monitoring recommendations.
SARS-CoV-2 (COVID-19) vaccines: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
SARS-CoV-2 Virus (COVID-19) Adenovirus Vector Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
SARS-CoV-2 Virus (COVID-19) mRNA Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
SARS-CoV-2 Virus (COVID-19) Recombinant Spike Protein Nanoparticle Vaccine: (Moderate) Patients receiving immunosuppressant medications may have a diminished response to the SARS-CoV-2 virus vaccine. When feasible, administer indicated vaccines prior to initiating immunosuppressant medications. Counsel patients receiving immunosuppressant medications about the possibility of a diminished vaccine response and to continue to follow precautions to avoid exposure to SARS-CoV-2 virus after receiving the vaccine.
Selpercatinib: (Major) Monitor ECGs more frequently for QT prolongation if coadministration of selpercatinib with vorinostat is necessary due to the risk of additive QT prolongation. Concentration-dependent QT prolongation has been observed with selpercatinib therapy. Vorinostat therapy is associated with a risk of QT prolongation.
Sertraline: (Moderate) Concomitant use of sertraline and vorinostat may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP. The degree of QT prolongation associated with sertraline is not clinically significant when administered within the recommended dosage range; QT prolongation has been described at 2 times the maximum recommended dose.
Sevoflurane: (Major) Vorinostat and halogenated anesthetics are associated with a risk of QT prolongation and should be used cautiously in combination.
Siponimod: (Major) In general, do not initiate treatment with siponimod in patients receiving vorinostat due to the potential for QT prolongation. Consult a cardiologist regarding appropriate monitoring if siponimod use is required. Siponimod therapy prolonged the QT interval at recommended doses in a clinical study. Vorinostat therapy is associated with a risk of QT prolongation.
Sodium Phenylbutyrate: (Major) Avoid coadministration of sodium phenylbutyrate and vorinostat. Concomitant use may result in unpredictable effects, resulting in increased toxicities or a reduction in efficacy. Sodium phenylbutyrate and vorinostat are inhibitors of histone deacetylase (HDAC).
Sodium Phenylbutyrate; Taurursodiol: (Major) Avoid coadministration of sodium phenylbutyrate and vorinostat. Concomitant use may result in unpredictable effects, resulting in increased toxicities or a reduction in efficacy. Sodium phenylbutyrate and vorinostat are inhibitors of histone deacetylase (HDAC).
Sodium Stibogluconate: (Moderate) Concomitant use of sodium stibogluconate and vorinostat may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Solifenacin: (Moderate) Solifenacin has been associated dose-dependent prolongation of the QT interval. Torsades de pointes (TdP) has been reported with post-marketing use, although causality was not determined. This should be taken into consideration when prescribing solifenacin to patients taking other drugs that are associated with QT prolongation. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with solifenacin include vorinostat.
Sorafenib: (Major) Avoid coadministration of sorafenib with vorinostat due to the risk of additive QT prolongation. If concomitant use is unavoidable, monitor electrocardiograms and correct electrolyte abnormalities. An interruption or discontinuation of sorafenib therapy may be necessary if QT prolongation occurs. Vorinostat therapy is associated with a risk of QT prolongation. Sorafenib is also associated with QTc prolongation.
Sotalol: (Major) Concomitant use of vorinostat and sotalol increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Spironolactone; Hydrochlorothiazide, HCTZ: (Moderate) Use vorinostat and thiazide diuretics together with caution; the risk of QT prolongation and arrhythmias may be increased if electrolyte abnormalities occur. Thiazide diuretics may cause electrolyte imbalances including low potassium; hypomagnesemia, hypokalemia, or hypocalcemia may increase the risk of QT prolongation with vorinostat. Frequently monitor serum electrolytes if concomitant use of these drugs is necessary.
Sunitinib: (Moderate) Monitor for evidence of QT prolongation if sunitinib is administered with vorinostat. Vorinostat therapy is associated with a risk of QT prolongation. Sunitinib can prolong the QT interval.
Tacrolimus: (Moderate) Consider ECG and electrolyte monitoring periodically during treatment if tacrolimus is administered with vorinostat. Tacrolimus may prolong the QT interval and cause torsade de pointes (TdP). Vorinostat therapy is associated with a risk of QT prolongation.
Tamoxifen: (Moderate) Concomitant use of tamoxifen and vorinostat may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Telavancin: (Moderate) Due to increased risk of QT interval prolongation and torsade de pointes (TdP), use caution if telavancin is administered with vorinostat. Both telavancin and vorinostat have been associated with QT prolongation.
Telmisartan; Hydrochlorothiazide, HCTZ: (Moderate) Use vorinostat and thiazide diuretics together with caution; the risk of QT prolongation and arrhythmias may be increased if electrolyte abnormalities occur. Thiazide diuretics may cause electrolyte imbalances including low potassium; hypomagnesemia, hypokalemia, or hypocalcemia may increase the risk of QT prolongation with vorinostat. Frequently monitor serum electrolytes if concomitant use of these drugs is necessary.
Tenecteplase: (Moderate) Due to the thrombocytopenic effects of vorinostat, an additive risk of bleeding may be seen in patients receiving concomitant thrombolytic agents.
Tetrabenazine: (Major) Tetrabenazine causes a small increase in the corrected QT interval (QTc). The manufacturer recommends avoiding concurrent use of tetrabenazine with other drugs known to prolong QTc. Vorinostat therapy is associated with a risk of QT prolongation and should be used cautiously with tetrabenazine.
Thiazide diuretics: (Moderate) Use vorinostat and thiazide diuretics together with caution; the risk of QT prolongation and arrhythmias may be increased if electrolyte abnormalities occur. Thiazide diuretics may cause electrolyte imbalances including low potassium; hypomagnesemia, hypokalemia, or hypocalcemia may increase the risk of QT prolongation with vorinostat. Frequently monitor serum electrolytes if concomitant use of these drugs is necessary.
Thioridazine: (Contraindicated) Thioridazine is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Thioridazine is considered contraindicated for use along with agents that, when combined with a phenothiazine, may prolong the QT interval and increase the risk of TdP, and/or cause orthostatic hypotension. Vorinostat therapy is associated with a risk of QT prolongation. Because of the potential for TdP, use of thioridazine with vorinostat is contraindicated.
Thrombolytic Agents: (Moderate) Due to the thrombocytopenic effects of vorinostat, an additive risk of bleeding may be seen in patients receiving concomitant thrombolytic agents.
Ticagrelor: (Moderate) Carefully monitor patients for signs and symptoms of bleeding during coadministration of ticagrelor and vorinostat. Due to the thrombocytopenic effects of vorinostat, an additive risk of bleeding may occur in patients taking platelet inhibitors.
Tolterodine: (Major) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering tolterodine with vorinostat. Tolterodine has been associated with dose-dependent prolongation of the QT interval, especially in poor CYP2D6 metabolizers. Vorinostat therapy is also associated with a risk of QT prolongation.
Toremifene: (Major) Avoid coadministration of vorinostat with toremifene if possible due to the risk of additive QT prolongation. If concomitant use is unavoidable, closely monitor ECGs for QT prolongation and monitor electrolytes; correct hypokalemia or hypomagnesemia prior to administration of toremifene. Toremifene has been shown to prolong the QTc interval in a dose- and concentration-related manner. Vorinostat therapy is also associated with a risk of QT prolongation.
Torsemide: (Moderate) Use vorinostat and loop diuretics together with caution; the risk of QT prolongation and arrhythmias may be increased if electrolyte abnormalities occur. Loop diuretics may cause electrolyte imbalances including low potassium; hypomagnesemia, hypokalemia, or hypocalcemia may increase the risk of QT prolongation with vorinostat. Frequently monitor serum electrolytes if concomitant use of these drugs is necessary.
Trazodone: (Major) Concomitant use of vorinostat and trazodone increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Triamcinolone: (Moderate) Use vorinostat and corticosteroids together with caution; the risk of QT prolongation and arrhythmias may be increased if electrolyte abnormalities occur. Corticosteroids may cause electrolyte imbalances; hypomagnesemia, hypokalemia, or hypocalcemia and may increase the risk of QT prolongation with vorinostat. Frequently monitor serum electrolytes if concomitant use of these drugs is necessary.
Triamterene; Hydrochlorothiazide, HCTZ: (Moderate) Use vorinostat and thiazide diuretics together with caution; the risk of QT prolongation and arrhythmias may be increased if electrolyte abnormalities occur. Thiazide diuretics may cause electrolyte imbalances including low potassium; hypomagnesemia, hypokalemia, or hypocalcemia may increase the risk of QT prolongation with vorinostat. Frequently monitor serum electrolytes if concomitant use of these drugs is necessary.
Triclabendazole: (Moderate) Concomitant use of triclabendazole and vorinostat may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Trifluoperazine: (Minor) Vorinostat therapy is associated with a risk of QT prolongation. Drugs with a possible risk for QT prolongation that should be used cautiously with vorinostat include trifluoperazine. Theoretically, trifluoperazine may increase the risk of QT prolongation if coadministered with drugs with a possible risk for QT prolongation.
Triptorelin: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., triptorelin) outweigh the potential risks of QT prolongation in patients receiving vorinostat. Vorinostat therapy is associated with a risk of QT prolongation. Androgen deprivation therapy may also prolong the QT/QTc interval.
Tuberculin Purified Protein Derivative, PPD: (Moderate) Immunosuppressives may decrease the immunological response to tuberculin purified protein derivative, PPD. This suppressed reactivity can persist for up to 6 weeks after treatment discontinuation. Consider deferring the skin test until completion of the immunosuppressive therapy.
Valproic Acid, Divalproex Sodium: (Major) Severe thrombocytopenia and GI bleeding have been reported during concomitant administration of vorinostat and valproic acid. Monitor platelet counts every 2 weeks for the first 2 months of vorinostat therapy, and then monthly or as clinically indicated.
Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Use vorinostat and thiazide diuretics together with caution; the risk of QT prolongation and arrhythmias may be increased if electrolyte abnormalities occur. Thiazide diuretics may cause electrolyte imbalances including low potassium; hypomagnesemia, hypokalemia, or hypocalcemia may increase the risk of QT prolongation with vorinostat. Frequently monitor serum electrolytes if concomitant use of these drugs is necessary.
Vandetanib: (Major) Avoid coadministration of vandetanib with vorinostat due to an increased risk of QT prolongation and torsade de pointes (TdP). If concomitant use is unavoidable, monitor ECGs for QT prolongation and monitor electrolytes; correct hypocalcemia, hypomagnesemia, and/or hypomagnesemia prior to vandetanib administration. An interruption of vandetanib therapy or dose reduction may be necessary for QT prolongation. Vandetanib can prolong the QT interval in a concentration-dependent manner; TdP and sudden death have been reported in patients receiving vandetanib. Vorinostat therapy is also associated with a risk of QT prolongation.
Vardenafil: (Moderate) Concomitant use of vardenafil and vorinostat may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Vemurafenib: (Major) Vemurafenib has been associated with QT prolongation. If vemurafenib and another drug that is associated with a possible risk for QT prolongation and torsade de pointes (TdP), such as vorinostat, must be coadministered, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation.
Venlafaxine: (Moderate) Concomitant use of venlafaxine and vorinostat may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Voclosporin: (Moderate) Concomitant use of voclosporin and vorinostat may increase the risk of QT prolongation. Consider interventions to minimize the risk of progression to torsade de pointes (TdP), such as ECG monitoring and correcting electrolyte abnormalities, particularly in patients with additional risk factors for TdP. Voclosporin has been associated with QT prolongation at supratherapeutic doses. Vorinostat therapy is associated with a risk of QT prolongation.
Vonoprazan; Amoxicillin; Clarithromycin: (Major) Clarithromycin is associated with an established risk for QT prolongation and torsades de pointes (TdP). Clarithromycin should be used cautiously with other medications which may prolong the QT interval including vorinostat.
Vorapaxar: (Moderate) Carefully monitor patients for signs and symptoms of bleeding during coadministration of vorapaxar and vorinostat. Due to the thrombocytopenic effects of vorinostat, an additive risk of bleeding may occur in patients taking platelet inhibitors.
Voriconazole: (Moderate) Caution is advised when administering voriconazole with vorinostat as concurrent use may increase the risk of QT prolongation. Voriconazole has been associated with QT prolongation and rare cases of torsade de pointes. Vorinostat therapy is also associated with a risk of QT prolongation.
Warfarin: (Moderate) Use vorinostat and warfarin together with caution; concomitant use may result in prolonged prothrombin time (PT) and International Normalized Ratio (INR) and an increased risk of bleeding. Monitor PT and INR more frequently if use of both drugs is required. Prolonged PT and INR have occurred in patients who received vorinostat in combination with coumarin-derivative anticoagulants.
Ziprasidone: (Major) Concomitant use of ziprasidone and vorinostat should be avoided due to the potential for additive QT prolongation. Clinical trial data indicate that ziprasidone causes QT prolongation; there are postmarketing reports of torsade de pointes (TdP) in patients with multiple confounding factors. Vorinostat therapy is associated with a risk of QT prolongation.
Vorinostat is a potent histone deacetylase (HDAC) inhibitor. Vorinostat inhibits HDAC1, HDAC2, HDAC3, and HDAC6 enzymes at nanomolar concentrations (IC50 < 86 nM). Histone deacetylases are the enzymes that catalyze the removal of acetyl groups from the lysine residues of proteins, including histones and transcription factors. Overexpression of HDACs or an abnormal recruitment of HDACs to oncogenic transcription factors is present in some cancer cells. This causes hypoacetylation of core nucleosomal histones resulting in a condensed chromatin structure and repression of gene transcription. Inhibition of HDAC activity produces an accumulation of acetyl groups on the histone lysine residues resulting in an open chromatin structure and transcriptional activation. In many different malignant cell lines, HDAC inhibitors have been shown to activate differentiation, inhibit the cell cycle, and induce apoptosis. In vivo, HDAC inhibitors have exhibited stimulation of the immune system and blockage of angiogenesis. The exact mechanism of the antineoplastic effect of HDAC inhibitors, including vorinostat, has not been determined. However, induction of histone hyperacetylation and modulation of gene transcription are thought to be primarily responsible for HDAC inhibitor activity.
Vorinostat is administered orally. It is approximately 71% bound to plasma proteins.
Vorinostat is eliminated primarily by metabolism with < 1% of the dose recovered in the urine. Metabolism occurs in the liver via glucuronidation and via hydrolysis followed by beta-oxidation. Two inactive metabolites are measured in plasma: the O-glucuronide of vorinostat and 4-anilino-4-oxobutanoic acid. In vitro studies using human liver microsomes indicate negligible biotransformation by the hepatic cytochrome P450 system. The mean terminal half-life for vorinostat and the O-glucuronide metabolite is roughly 2 hours, while the half-life of the 4-anilino-4-oxobutanoic acid is roughly 11 hours.
Affected cytochrome P450 isoenzymes and drug transporters: none
-Route-Specific Pharmacokinetics
Oral Route
The extent of oral absorption of vorinostat as well as rate of absorption is increased when administered with a high-fat meal. A 33% increase in extent of vorinostat absorption is seen when vorinostat is administered with food vs in the fasted state (5.5 +/- 1.8 microM-hour vs 4.2 +/- 1.9 microM-hour, respectively); time to maximum concentration (Tmax) was increased by 2.5 hours when vorinostat is administered with food vs fasting (4 hours vs 1.5 hours, respectively). Although these changes are not expected to be clinically significant, it is recommended vorinostat be given with food.
-Special Populations
Hepatic Impairment
The effect of hepatic impairment on vorinostat exposure was evaluated in a pharmacokinetic (PK) study in patients with non-cutaneous T-cell lymphoma (CTCL) cancers who had mild (total bilirubin level > 1-1.5X the upper limit of normal (ULN) OR total bilirubin level <= ULN and AST level > ULN), moderate (total bilirubin level of 1.5 to <= 3X ULN), and severe (total bilirubin level > 3X ULN) hepatic impairment. Compared with patients who had normal liver function, the mean AUC increased by 50% in patients with mild and moderate hepatic impairment and by 66% in patients with severe hepatic impairment following a single, oral 400-mg vorinostat dose. In another PK analysis, multiple daily vorinostat doses were evaluated in patients with non-CTCL cancers and mild (400 mg/day), moderate (300 mg/day), and severe (200 mg/day) hepatic impairment. Grade 3 or 4 adverse event rates were similar in all patients; grade 3 or 4 thrombocytopenia was the most commonly reported toxicity in this analysis. Based on data from 42 patients with varying degrees of hepatic impairment, an initial dosage adjustment is recommended in patients with mild to moderate hepatic impairment. No manufacturer dosing recommendation is provided for patients with severe hepatic impairment; however, these patients have not been treated with vorinostat doses exceeding 200 mg/day.
Renal Impairment
Vorinostat has not been evaluated in patients with renal impairment. Renal excretion does not play a role in the elimination of vorinostat.
Pediatrics
Vorinostat has not been evaluated in pediatric patients.
Geriatric
Age does not appear to have meaningful effects on the pharmacokinetics of vorinostat.
Gender Differences
Gender does not appear to have meaningful effects on the pharmacokinetics of vorinostat.
Ethnic Differences
Race does not appear to have meaningful effects on the pharmacokinetics of vorinostat.