Dolasetron is an oral and intravenous serotonin (5-HT3) receptor antagonist that is used in adult and pediatric patients 2 years of age and older. The oral tablets are indicated for the prevention of chemotherapy-induced nausea/vomiting (CINV); the injection is only indicated for the prevention and treatment of post-operative nausea/vomiting (PONV). Most of the activity of dolasetron is due to the active metabolite, hydrodolasetron, which is 50-fold more potent than dolasetron. The efficacy of dolasetron is comparable to other 5-HT3 antiemetics such as granisetron and ondansetron. However, dolasetron has been associated with dose-dependent cardiovascular safety concerns such as QT, PR, and QRS interval prolongation and torsade de pointes; the injection is contraindicated for CINV prophylaxis as the dose and drug exposure are higher than for other uses. The American Society of Clinical Oncology (ASCO) guidelines recommend that adult patients who are treated with moderate to high-emetic-risk chemotherapy agents should be offered a 3-drug combination of a 5-HT3 receptor antagonist, a neurokinin 1 (NK1) receptor antagonist, and dexamethasone; olanzapine is also added to the 3-drug combination during use of high-emetic-risk agents. Children receiving moderate to high-emetic-risk agents should be offered a 2-drug combination of a 5-HT3 receptor antagonist and dexamethasone; aprepitant is also added to the 2-drug combination during use of high-emetic-risk agents.
General Administration Information
For storage information, see the specific product information within the How Supplied section.
Route-Specific Administration
Oral Administration
-May be administered without regard to meals.
-For pediatric patients, dolasetron injection may be mixed in apple or apple-grape juice for oral dosing. The diluted product may be kept for up to 2 hours at room temperature. If the IV injection is used for oral administration in children, the dose is the same as for the tablets.
Injectable Administration
-Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.
Intravenous Administration
-Dolasetron may be administered by direct IV injection or as an intravenous infusion.
Direct IV injection
-Administer IV at a rate not to exceed 100 mg over 30 seconds.
Intravenous infusion
-Dilute dose in a compatible IV solution (0.9% Sodium Chloride , 5% Dextrose, 5% Dextrose and 0.45% Sodium Chloride, 5% Dextrose and Lactated Ringer's, Lactated Ringer's, and mannitol 10% injection) to 50 mL.
-Infuse over a period of 15 minutes.
-Diluted dolasetron is stable for up to 24 hours when stored under normal lighting conditions at room temperature, and for up to 48 hours under refrigeration.
Pain was reported in 0% and 3.1% of adult cancer patients who received oral dolasetron 25 mg (n = 235) and 100 mg (n = 227), respectively, for the prevention of chemotherapy induced nausea and vomiting in clinical trials.
Elevated hepatic enzymes (AST, ALT) occurred in less than 1% of adult patients who received oral or IV dolasetron in clinical trials. The transaminase level increases were transient, did not appear to be related to dose or duration of treatment, and were not associated with symptomatic hepatic disease. Other hepatic related adverse effects that were reported in less than 2% of patients include hyperbilirubinemia and increased gamma glutamyl transferase (GGT) and alkaline phosphatase levels.
Injection site reaction (consisting of local pain or burning), peripheral ischemia, and thrombophlebitis/phlebitis were reported in less than 2% of adult patients who received IV dolasetron in clinical trials.
Rash (unspecified) and increased sweating (hyperhidrosis) occurred in less than 2% of adult patients who received oral or IV dolasetron in clinical trials.
Dose dependent QT prolongation and QRS and PR prolongation have been reported with oral or IV dolasetron use. Second and third degree AV block, cardiac arrest, and serious ventricular arrhythmias (some fatal) have occurred in adults and pediatric patients receiving dolasetron. Do not use dolasetron in patients with congenital long QT syndrome, hypokalemia, hypomagnesemia, and complete heart block or risk of complete heart block (unless a pacemaker is in place); use with caution in patients with a history of (or risk for) cardiac conduction abnormalities. Monitor electrolytes prior to and during therapy and correct electrolyte abnormalities before starting therapy. ECG monitoring is recommended in elderly patients and patients with congestive heart failure, bradycardia, or renal impairment. Ventricular tachycardia, ventricular fibrillation, and torsade de pointes have been reported following IV administration in post-marketing surveillance.
Bradycardia was reported in 5.1% and 4% of adult cancer patients who received oral dolasetron 25 mg (n = 235) and 100 mg (n = 227), respectively, for the prevention of chemotherapy induced nausea and vomiting in clinical trials; additionally, sinus tachycardia was reported in 3% and 2.6% of patients, respectively. Tachycardia occurred in 2.2% of patients who received 100 mg PO (n = 228) compared with 0.9% of patients who received placebo (n = 231) for the prevention of postoperative nausea and vomiting in clinical trials. Other cardiovascular adverse effects that were reported in less than 2% of adult patients who received oral or IV dolasetron in clinical trials include edema, peripheral edema, myocardial ischemia, sinus arrhythmia, hypotension, orthostatic hypotension, AV block (Mobitz I), chest pain (unspecified), syncope, severe bradycardia, palpitations, and symptomatic ECG changes such as bradycardia, tachycardia, T-wave changes, ST-T wave changes, extrasystole, bundle-branch block, poor R-wave progression, nodal arrhythmia, U wave changes, atrial flutter, and atrial fibrillation. Hypotension, bradycardia, and syncope have occurred following IV administration; additionally, wide complex tachycardia has been reported following IV dolasetron in post-marketing surveillance.
Headache was reported in 17.9% and 22.9% of adult cancer patients who received oral dolasetron 25 mg (n = 235) and 100 mg (n = 227), respectively, for the prevention of chemotherapy induced nausea and vomiting in clinical trials; additionally, dizziness was reported in 1.3% and 3.1% of patients, respectively. Headache occurred in 7% of patients who received 100 mg PO (n = 228) compared with 4.8% of patients who received placebo (n = 231) for the prevention of postoperative nausea and vomiting in clinical trials; dizziness was also reported more often in the dolasetron arm compared with the placebo arm (4.4% vs 0%). Headache was reported in 9.4% of patients who received 12.5 mg IV (n = 615) compared with 6.9% of patients who received placebo (n = 739) for the prevention of postoperative nausea and vomiting in clinical trials; dizziness occurred in 5.5% of patients who received IV dolasetron compared with 3.1% of patients who received placebo. Other nervous system adverse effects that were reported in less than 2% of adult patients who received oral or IV dolasetron in clinical trials include flushing, vertigo, paresthesias, tremor, ataxia, and twitching.
Diarrhea was reported in 2.1% and 5.3% of adult cancer patients who received oral dolasetron 25 mg (n = 235) and 100 mg (n = 227), respectively, for the prevention of chemotherapy induced nausea and vomiting in clinical trials; additionally, dyspepsia was reported in 3% and 2.2% of patients, respectively. Other gastrointestinal adverse effects that were reported in less than 2% of adult patients who received oral or IV dolasetron in clinical trials include constipation, dyspepsia, abdominal pain, anorexia, and pancreatitis.
Chills/shivering was reported in 1.3% and 2.2% of adult cancer patients who received oral dolasetron 25 mg (n = 235) and 100 mg (n = 227), respectively, for the prevention of chemotherapy induced nausea and vomiting in clinical trials. Chills/shivering were reported in less than 2% of adult patients undergoing surgery who received oral or IV dolasetron in clinical trials. Fever was reported in 3.5% of patients who received 100 mg PO (n = 228) compared with 3% of patients who received placebo (n = 231) for the prevention of postoperative nausea and vomiting in clinical trials.
Oliguria occurred in 2.6% of patients who received oral dolasetron 100 mg (n = 228) compared with 1.3% of patients who received placebo (n = 231) for the prevention of postoperative nausea and vomiting in clinical trials. Other urinary system adverse effects that were reported in less than 2% of adult patients who received oral or IV dolasetron in clinical trials include dysuria, polyuria, and acute renal failure (unspecified).
Fatigue was reported in 2.6% and 5.7% of adult cancer patients who received oral dolasetron 25 mg (n = 235) and 100 mg (n = 227), respectively, for the prevention of chemotherapy induced nausea and vomiting in clinical trials.
Taste perversion (dysgeusia) occurred in less than 2% of adult patients who received oral or IV dolasetron in clinical trials.
Photophobia and abnormal vision occurred in less than 2% of adult patients who received oral or IV dolasetron in clinical trials.
Tinnitus occurred in less than 2% of adult patients who received oral or IV dolasetron in clinical trials.
Hematologic adverse events that occurred in less than 2% of adult patients who received oral or IV dolasetron in clinical trials include hematuria, epistaxis, prolonged bleeding time (prolonged prothrombin time (PT) and partial thromboplastin time (PTT)), anemia, purpura/hematoma, and thrombocytopenia.
Psychiatric adverse events that occurred in less than 2% of adult patients who received oral or IV dolasetron in clinical trials include agitation, sleep disorder, depersonalization, confusion, anxiety, and abnormal dreaming.
Anaphylactoid reactions, facial edema (angioedema), and urticaria have been reported in less than 2% of adult patients who received oral or IV dolasetron in clinical trials.
Myalgia and arthralgia have been reported in less than 2% of adult patients who received oral or IV dolasetron in clinical trials.
Dyspnea and bronchospasm have been reported in less than 2% of adult patients who received oral or IV dolasetron in clinical trials.
Serotonin syndrome has been reported with 5-HT3 receptor antagonists, such as dolasetron, during concurrent use of other medications known to increase CNS or peripheral serotonin levels or during overdose. Some of the reported cases were fatal; most occurred in a post-anesthesia care unit or infusion center. If serotonin syndrome becomes evident during treatment, discontinue dolasetron and any other serotonergic agents and initiate appropriate medical treatment. Serotonin syndrome is a range of signs and symptoms that can include mental status changes (e.g., agitation, hallucinations, delirium, coma), gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea), autonomic instability (e.g., tachycardia, labile blood pressure, dizziness, diaphoresis, flushing, hyperthermia), neuromuscular symptoms (e.g., tremor, rigidity, myoclonus, hyperreflexia, incoordination), and/or seizures. Cases consistent with serotonin syndrome have been reported in pediatric patients after inadvertent overdose of oral ondansetron (estimated ingestion > 5 mg/kg). Symptoms reported in these cases included somnolence, agitation, tachycardia, tachypnea, hypertension, flushing, mydriasis, diaphoresis, myoclonic movements, horizontal nystagmus, hyperreflexia, and seizures. Patients required supportive care, including intubation in some cases, with complete recovery in 1-2 days.
Do not use dolasetron in patients with a known dolasetron hypersensitivity. Although cross-sensitivity reactions have been reported in patients who have received other 5-HT3 receptor antagonists, these reactions have not been seen with dolasetron. Nevertheless, use dolasetron with caution in patients with a known hypersensitivity to related drugs (e.g., granisetron hypersensitivity, palonosetron hypersensitivity, or ondansetron hypersensitivity). Furthermore, it has been hypothesized that antagonism at serotonin (5HT) receptors, and the subsequent increased concentrations of serotonin, increase the risk of developing bronchospasm and/or vasoconstriction. There have been several reports of anaphylactic/anaphylactoid reactions associated with the use of drugs in this class. It is not clear at this time if these reactions are due to the use of the serotonin antagonist alone or due to a drug interaction between the serotonin antagonist and a chemotherapeutic agent. Nevertheless, clinicians should not overlook this possibility.
Dolasetron can cause dose-dependent ECG interval changes (PR and QTc prolongation and QRS widening), second or third degree atrioventricular block (AV block), cardiac arrest, and serious ventricular arrhythmias. In December 2010, the FDA announced that because of the risk of QT prolongation from increased drug exposure, dolasetron injection is contraindicated for use for the prevention of chemotherapy induced nausea/vomiting (CINV), an indication for which it was previously FDA-approved. ECG interval changes including QT, QRS, and PR interval prolongation have been noted during clinical evaluation of IV dolasetron. Torsade de pointes has also been reported in some patients receiving dolasetron injection. Dolasetron injection can continue to be used for post-operative nausea and vomiting (PONV), since the lower doses used in PONV are less likely to affect the electrical activity of the heart. In addition, oral formulations will continue to carry indications for the prevention of CINV, since it is associated with a smaller risk of developing an abnormal heart rhythm as compared with the parenteral form. Associated changes to cardiac electrical activity are related in magnitude and frequency to blood concentrations of the active metabolite (hydrodolasetron) and are self-limiting with declining blood concentrations. Some patients have interval prolongations for 24 hours or longer. Interval prolongation may lead to cardiovascular consequences, including heart block or cardiac arrhythmias; these have rarely been reported. Avoid dolasetron in patients with congenital long QT syndrome, hypokalemia, or hypomagnesemia. Before initiating dolasetron therapy, hypokalemia and hypomagnesemia should be corrected. Electrolytes should be monitored as clinically indicated thereafter. In addition, dolasetron should be avoided in patients with complete heart block or at risk for complete heart block, unless they have an implanted pacemaker. Dolasetron should be administered with caution in patients with underlying structural heart disease or in patients who have or may develop prolongation of cardiac conduction intervals, particularly QT prolongation. Patients who may be at risk include patients with sick sinus syndrome, atrial fibrillation with slow ventricular response, myocardial ischemia, those with pre-existing cardiac disease, patients with renal impairment, and those who have received high cumulative doses of anthracyclines. An electrocardiogram (ECG) is warranted for at risk patients receiving dolasetron. Use dolasetron with caution in patients with conditions that may increase the risk of QT prolongation including bradycardia, AV block, heart failure, stress-related cardiomyopathy, myocardial infarction, stroke, hypocalcemia, or in patients receiving medications known to prolong the QT interval or cause electrolyte imbalances. Females, people 65 years and older, 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. Patients experiencing signs and symptoms of an abnormal heart rate or rhythm while taking dolasetron should be advised to contact their healthcare provider; clinicians are encouraged to report related adverse events to the FDA MedWatch program.
Dolasetron has been used in children age 2 to 16 years and has, overall, has been well tolerated. However, dolasetron should be used cautiously in pediatric patients who have preexisting, or are at risk of developing, prolonged cardiac conduction intervals, particularly QTc. Rarely, cases of sustained supraventricular and ventricular arrhythmias, cardiac arrest leading to death, and myocardial infarction have been reported in children and adolescents taking dolasetron. No efficacy information has been collected in the pediatric postoperative nausea/vomiting studies. There is no experience in neonates, infants, or children under 2 years of age.
In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. Because dolasetron can cause QT interval prolongation, geriatric patients taking dolasetron may be at increased risk for serious abnormal cardiac rhythms. Therefore, cautious administration and careful monitoring, including electrocardiogram (ECG) monitoring, is recommended. Also, in controlled clinical trials in the prevention of chemotherapy-induced nausea and vomiting, 723 (32%) of 2264 patients were 65 years of age or older. Of the 723 elderly patients in the trial, 563 received oral dolasetron. No differences in safety or effectiveness have been observed between elderly and younger patients. Controlled clinical studies in the prevention and treatment of post-operative nausea and vomiting (PONV) did not include sufficient numbers of patients aged 65 years or older. Only 57 (2%) geriatric patients out of 3289 total patients participated in the controlled PONV trials evaluating differences between the elderly and younger patients. Other reported clinical experiences have not identified differences in responses between geriatric and younger patients.
There are no adequate and well-controlled studies with dolasetron in pregnant women. Animal studies have not revealed any teratogenic effects associated with dolasetron. Because animal studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed. Evidence is limited on the safety or efficacy of the serotonin 5-HT3 inhibitors for nausea and vomiting of pregnancy. Alternatives in this class to dolasetron exist for consideration for use during pregnancy, due to more published data in this population. The American College of Obstetricians and Gynecologists (ACOG) practice bulletin includes ondansetron as a third-line pharmacologic treatment option for nausea and vomiting of pregnancy in patients who have failed other therapies.
According to the manufacturer, it is not known whether dolasetron is excreted in human milk. However, because of its low molecular weight, transfer into breast milk should be expected. Caution should be exercised when administering dolasetron to a breast-feeding woman. Consider the benefits of breast-feeding, the risk of potential infant drug exposure, and the risk of an untreated or inadequately treated condition. If a breast-feeding infant experiences an adverse effect related to a maternally administered drug, healthcare providers are encouraged to report the adverse effect to the FDA.
For chemotherapy-induced nausea/vomiting prophylaxis (CINV prophylaxis):
NOTE: In December 2010, the FDA announced that because of the risk of QT prolongation, dolasetron injection is longer indicated for chemotherapy-induced nausea/vomiting (CINV) prophylaxis.
Oral dosage:
Adults: 100 mg PO administered within 1 hour before chemotherapy.
Children 2-11 and Adolescents: 1.8 mg/kg PO (not to exceed 100 mg) administered within 1 hour before chemotherapy.
Neonates, Infants, and Children < 2 years: Safety and efficacy have not been established.
For the treatment of post-operative nausea/vomiting (PONV):
Intravenous dosage:
Adults: 12.5 mg IV as a single dose. Administer when PONV presents.
Children >= 2 years and Adolescents : 0.35 mg/kg IV (not to exceed 12.5 mg) as a single dose when PONV presents.
Neonates, Infants, and Children < 2 years: Safety and efficacy have not been established.
For post-operative nausea/vomiting (PONV) prophylaxis:
Intravenous dosage:
Adults: 12.5 mg IV, administered 15 minutes before the cessation of anesthesia. Routine prophylaxis is not recommended for all patients; however, in patients where nausea and/or vomiting must be avoided postoperatively, dolasetron is recommended even where the incidence of postoperative nausea and/or vomiting is low. Do not rechallenge a patient who has failed a previous trial of a 5-HT3 receptor antagonist with a repeat dose of dolasetron.
Children >= 2 years and Adolescents: 0.35 mg/kg IV (not to exceed 12.5 mg), administered 15 minutes before the cessation of anesthesia. Routine prophylaxis is not recommended for all patients; however, in patients where nausea and/or vomiting must be avoided postoperatively, dolasetron is recommended even where the incidence of postoperative nausea and/or vomiting is low. Do not rechallenge a patient who has failed a previous trial of a 5-HT3 receptor antagonist with a repeat dose of dolasetron.
Neonates, Infants, and Children < 2 years : Safety and efficacy have not been established.
Maximum Dosage Limits:
-Adults
100 mg/dose PO; 12.5 mg/dose IV (for prevention/treatment of post-operative nausea/vomiting). Information on maximum total daily dose is unavailable.
-Geriatric
100 mg/dose PO; 12.5 mg/dose IV (for prevention/treatment of post-operative nausea/vomiting). Information on maximum total daily dose is unavailable.
-Adolescents
1.8 mg/kg PO (Max: 100 mg/dose) for prevention of chemotherapy-induced nausea/vomiting; 0.35 mg/kg IV (Max: 12.5 mg/dose) for prevention/treatment of post-op nausea/vomiting.
-Children
2 years or older: 1.8 mg/kg PO (Max: 100 mg/dose) for prevention of chemotherapy-induced nausea/vomiting; 0.35 mg/kg IV (Max: 12.5 mg/dose) for prevention/treatment of post-op nausea/vomiting.
Younger than 2 years: Safety and efficacy have not been established.
-Infants
Safety and efficacy have not been established.
-Neonates
Safety and efficacy have not been established.
Patients with Hepatic Impairment Dosing
No dosage adjustments are needed.
Patients with Renal Impairment Dosing
No dosage adjustments are needed.
*non-FDA-approved indication
Acetaminophen; Caffeine; Dihydrocodeine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering dihydrocodeine with serotonin-receptor antagonists. The development of serotonin syndrome has been reported with 5-HT3 receptor antagonists, mostly when used in combination with other serotonergic medications. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Acetaminophen; Codeine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering codeine with serotonin-receptor antagonists. The development of serotonin syndrome has been reported with 5-HT3 receptor antagonists, mostly when used in combination with other serotonergic medications. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Acetaminophen; Hydrocodone: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering hydrocodone with serotonin-receptor antagonists. The development of serotonin syndrome has been reported with 5-HT3 receptor antagonists, mostly when used in combination with other serotonergic medications. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Acetaminophen; Oxycodone: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering oxycodone with serotonin-receptor antagonists. The development of serotonin syndrome has been reported with 5-HT3 receptor antagonists, mostly when used in combination with other serotonergic medications. Inform patients taking this combination of the possible increased risks and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Adagrasib: (Major) Concomitant use of adagrasib and dolasetron 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.
Alfentanil: (Moderate) If concomitant use of alfentanil and dolasetron is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Alfuzosin: (Moderate) Administer dolasetron with caution in combination with alfuzosin as concurrent use may increase the risk of QT prolongation. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram. Alfuzosin may also prolong the QT interval in a dose-dependent manner.
Aliskiren; Hydrochlorothiazide, HCTZ: (Moderate) Caution is advisable during concurrent use of dolasetron and thiazide diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with dolasetron.
Amiloride; Hydrochlorothiazide, HCTZ: (Moderate) Caution is advisable during concurrent use of dolasetron and thiazide diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with dolasetron.
Amiodarone: (Major) Concomitant use of amiodarone and dolasetron 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 dolasetron. Amisulpride causes dose- and concentration- dependent QT prolongation. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram.
Amlodipine; Celecoxib: (Moderate) Monitor patients closely for dolasetron-related adverse reactions and consider a dosage reduction of dolasetron if coadministration with celecoxib is necessary. Celecoxib may enhance the systemic exposure and toxicity of dolasetron. In vitro studies indicate that celecoxib is an inhibitor of CYP2D6. Dolasetron is a CYP2D6 substrate.
Amlodipine; Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Caution is advisable during concurrent use of dolasetron and thiazide diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with dolasetron.
Amoxicillin; Clarithromycin; Omeprazole: (Contraindicated) Clarithromycin is associated with an established risk for QT prolongation and torsades de pointes (TdP). Clarithromycin should be used cautiously with other agents known to cause QT prolongation. Agents with potential to prolong the QT interval include: dolasetron.
Anagrelide: (Major) Torsades de pointes (TdP) and ventricular tachycardia have been reported during post-marketing use of anagrelide. A cardiovascular examination, including an ECG, should be obtained in all patients prior to initiating anagrelide therapy. Monitor patients during anagrelide therapy for cardiovascular effects and evaluate as necessary. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with anagrelide include dolasetron.
Apomorphine: (Contraindicated) The concurrent use of apomorphine and serotonin-receptor antagonists is contraindicated due to the possibility of an excessive lowering of blood pressure and unconsciousness. Additionally, additive QT prolongation is possible during coadministration of apomorphine with dolasetron, granisetron, and ondansetron.
Aprepitant, Fosaprepitant: (Minor) Aprepitant, fosaprepitant is indicated for the prophylaxis of chemotherapy-induced nausea/vomiting in combination with a 5HT3 antagonist, one of which is dolasetron. Dolasetron is a CYP3A4 substrate. Aprepitant, when administered as a 3-day oral regimen (125 mg/80 mg/80 mg), is a moderate CYP3A4 inhibitor and inducer; substitution of fosaprepitant 115 mg IV on day 1 of the 3-day regimen may lessen the inhibitory effects of CYP3A4. The AUC of another CYP3A4 substrate, midazolam, was increased for several days after aprepitant dosing when the two drugs were coadministered; however, in clinical drug interaction studies, aprepitant did not have clinically important effects on the pharmacokinetics of hydrodolasetron (the active metabolite of dolasetron).
Aripiprazole: (Moderate) Concomitant use of aripiprazole and dolasetron 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.
Arsenic Trioxide: (Major) Avoid concomitant use of arsenic trioxide with other drugs, such as dolasetron, that may cause QT interval prolongation; discontinue or select an alternative drug that does not prolong the QT interval prior to starting arsenic trioxide therapy. Torsade de pointes (TdP), QT interval prolongation, and complete atrioventricular block have been reported with arsenic trioxide use. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram. If concomitant drug use is unavoidable, frequently monitor electrocardiograms.
Artemether; Lumefantrine: (Major) Due to a possible risk for QT prolongation and torsade de pointes (TdP) dolasetron and artemether; lumefantrine should be used together cautiously. Dolasetron has been associated with a dose-dependant prolongation in the QT, PR, and QRS intervals on an electrocardiogram. Use of dolasetron injection for the prevention of chemotherapy-induced nausea and vomiting is contraindicated because the risk of QT prolongation is higher with the doses required for this indication; when the injection is used at lower doses (i.e., those approved for post-operative nausea and vomiting) or when the oral formulation is used, the risk of QT prolongation is lower and caution is advised. Artemether; lumefantrine is an inhibitor and dolasetron is a substrate of the CYP2D6 isoenzyme; therefore, coadministration may lead to increased dolasetron concentrations. Furthermore, although there are no studies examining the effects of artemether; lumefantrine in patients receiving other QT prolonging drugs, coadministration of such drugs may result in additive QT prolongation. Concomitant use of artemether; lumefantrine with drugs that may prolong the QT interval, such as dolasetron, should be avoided. Consider ECG monitoring if dolasetron must be used with or after artemether; lumefantrine treatment.
Asenapine: (Major) Due to a possible risk for QT prolongation and torsade de pointes (TdP) dolasetron and asenapine should be avoided. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram. Asenapine has 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. Concomitant use may increase the risk for QT prolongation.
Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering codeine with serotonin-receptor antagonists. The development of serotonin syndrome has been reported with 5-HT3 receptor antagonists, mostly when used in combination with other serotonergic medications. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Aspirin, ASA; Oxycodone: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering oxycodone with serotonin-receptor antagonists. The development of serotonin syndrome has been reported with 5-HT3 receptor antagonists, mostly when used in combination with other serotonergic medications. Inform patients taking this combination of the possible increased risks and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Atazanavir; Cobicistat: (Moderate) The plasma concentrations of hydrodolasetron (primary dolasetron metabolite) may be elevated when dolasetron is administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as headache or cardiovascular effects, is recommended during coadministration. Cobicistat is a CYP3A4 and CYP2D6 inhibitor, while hydrodolasetron is a CYP3A4 and CYP2D6 substrate.
Atenolol: (Moderate) The clearance of hydrodolasetron, an active metabolite of dolasetron, is decreased when dolasetron mesylate is administered with atenolol.
Atenolol; Chlorthalidone: (Moderate) Caution is advisable during concurrent use of dolasetron and thiazide diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with dolasetron. (Moderate) The clearance of hydrodolasetron, an active metabolite of dolasetron, is decreased when dolasetron mesylate is administered with atenolol.
Atomoxetine: (Moderate) Concomitant use of atomoxetine and dolasetron 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.
Azilsartan; Chlorthalidone: (Moderate) Caution is advisable during concurrent use of dolasetron and thiazide diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with dolasetron.
Azithromycin: (Major) Avoid coadministration of azithromycin with dolasetron 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. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram.
Bedaquiline: (Major) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering bedaquiline with dolasetron. Bedaquiline has been reported to prolong the QT interval. Prior to initiating bedaquiline, obtain serum electrolyte concentrations and a baseline electrocardiogram (ECG). An ECG should also be performed at least 2, 12, and 24 weeks after starting bedaquiline therapy. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an ECG. Use of dolasetron injection for the prevention of chemotherapy-induced nausea and vomiting is contraindicated because the risk of QT prolongation is higher with the doses required for this indication; when the injection is used at lower doses (i.e., those approved for post-operative nausea and vomiting) or when the oral formulation is used, the risk of QT prolongation is lower and caution is advised.
Benazepril; Hydrochlorothiazide, HCTZ: (Moderate) Caution is advisable during concurrent use of dolasetron and thiazide diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with dolasetron.
Benzhydrocodone; Acetaminophen: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering benzhydrocodone with serotonin-receptor antagonists. The development of serotonin syndrome has been reported with 5-HT3 receptor antagonists, mostly when used in combination with other serotonergic medications. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Benzoic Acid; Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate: (Major) Because of the potential risk and severity of serotonin syndrome, use caution when administering dolasetron with other drugs that have serotonergic properties such as methylene blue. If serotonin syndrome is suspected, discontinue dolasetron and concurrent serotonergic agents and initiate appropriate medical treatment. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death.
Bismuth Subcitrate Potassium; Metronidazole; Tetracycline: (Moderate) Concomitant use of metronidazole and dolasetron 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 dolasetron 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) Caution is advisable during concurrent use of dolasetron and thiazide diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with dolasetron.
Bumetanide: (Moderate) Caution is advisable during concurrent use of dolasetron and loop diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with dolasetron.
Buprenorphine: (Major) Buprenorphine should be used cautiously and with close monitoring with dolasetron. Dolasetron has been associated with a dose-dependant prolongation in the QT, PR, and QRS intervals on an electrocardiogram. Buprenorphine has also been associated with QT prolongation and has a possible risk of torsade de pointes (TdP). FDA-approved labeling for some buprenorphine products recommend avoiding use with Class 1A and Class III antiarrhythmic medications while other labels recommend avoiding use with any drug that has the potential to prolong the QT interval. If these drugs are used together, consider the potential for additive effects on the QT interval.
Buprenorphine; Naloxone: (Major) Buprenorphine should be used cautiously and with close monitoring with dolasetron. Dolasetron has been associated with a dose-dependant prolongation in the QT, PR, and QRS intervals on an electrocardiogram. Buprenorphine has also been associated with QT prolongation and has a possible risk of torsade de pointes (TdP). FDA-approved labeling for some buprenorphine products recommend avoiding use with Class 1A and Class III antiarrhythmic medications while other labels recommend avoiding use with any drug that has the potential to prolong the QT interval. If these drugs are used together, consider the potential for additive effects on the QT interval.
Butalbital; Acetaminophen; Caffeine; Codeine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering codeine with serotonin-receptor antagonists. The development of serotonin syndrome has been reported with 5-HT3 receptor antagonists, mostly when used in combination with other serotonergic medications. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Butalbital; Aspirin; Caffeine; Codeine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering codeine with serotonin-receptor antagonists. The development of serotonin syndrome has been reported with 5-HT3 receptor antagonists, mostly when used in combination with other serotonergic medications. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Cabotegravir; Rilpivirine: (Moderate) Administer dolasetron with caution in combination with rilpivirine. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram.
Candesartan; Hydrochlorothiazide, HCTZ: (Moderate) Caution is advisable during concurrent use of dolasetron and thiazide diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with dolasetron.
Capsaicin; Metaxalone: (Moderate) Concomitant use of metaxalone and serotonin-receptor antagonists (5HT-3 receptor antagonists) may increase the risk for serotonin syndrome. Monitor patients for serotonin syndrome if concomitant use is necessary.
Captopril; Hydrochlorothiazide, HCTZ: (Moderate) Caution is advisable during concurrent use of dolasetron and thiazide diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with dolasetron.
Celecoxib: (Moderate) Monitor patients closely for dolasetron-related adverse reactions and consider a dosage reduction of dolasetron if coadministration with celecoxib is necessary. Celecoxib may enhance the systemic exposure and toxicity of dolasetron. In vitro studies indicate that celecoxib is an inhibitor of CYP2D6. Dolasetron is a CYP2D6 substrate.
Celecoxib; Tramadol: (Major) Because of the potential risk and severity of serotonin syndrome, use caution when administering dolasetron with other drugs that have serotonergic properties such as tramadol. If serotonin syndrome is suspected, discontinue dolasetron and concurrent serotonergic agents and initiate appropriate medical treatment. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. (Moderate) Monitor patients closely for dolasetron-related adverse reactions and consider a dosage reduction of dolasetron if coadministration with celecoxib is necessary. Celecoxib may enhance the systemic exposure and toxicity of dolasetron. In vitro studies indicate that celecoxib is an inhibitor of CYP2D6. Dolasetron is a CYP2D6 substrate.
Ceritinib: (Major) Avoid coadministration of ceritinib with dolasetron 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 QT prolongation. Dolasetron has also been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram.
Chloroquine: (Major) Avoid coadministration of chloroquine with dolasetron 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. Dolasetron has been associated with a dose-dependent prolongation of the QT, PR, and QRS intervals on an electrocardiogram.
Chlorothiazide: (Moderate) Caution is advisable during concurrent use of dolasetron and thiazide diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with dolasetron.
Chlorpheniramine; Codeine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering codeine with serotonin-receptor antagonists. The development of serotonin syndrome has been reported with 5-HT3 receptor antagonists, mostly when used in combination with other serotonergic medications. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Chlorpheniramine; Hydrocodone: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering hydrocodone with serotonin-receptor antagonists. The development of serotonin syndrome has been reported with 5-HT3 receptor antagonists, mostly when used in combination with other serotonergic medications. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Chlorpromazine: (Major) Due to a possible risk for QT prolongation and torsade de pointes (TdP), dolasetron and chlorpromazine should be used together cautiously. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram. Chlorpromazine, a phenothiazine, is associated with an established risk of QT prolongation and TdP. Concurrent use may further increase the risk for QT prolongation.
Chlorthalidone: (Moderate) Caution is advisable during concurrent use of dolasetron and thiazide diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with dolasetron.
Cimetidine: (Moderate) Coadministration of dolasetron and cimetidine, a nonselective inhibitor of cytochrome P450, increased the blood concentrations of dolasetron's active metabolite by 24%.
Ciprofloxacin: (Moderate) Concomitant use of ciprofloxacin and dolasetron 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) Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram. Because of the potential for torsade de pointes (TdP), use of cisapride with dolasetron is contraindicated.
Citalopram: (Major) Coadministration of citalopram and dolasetron is not recommended due to the potential risk of QT prolongation. If concurrent therapy is considered essential, ECG monitoring is recommended. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram. Citalopram causes dose-dependent QT interval prolongation. Concurrent use may increase the risk of QT prolongation.
Clarithromycin: (Contraindicated) Clarithromycin is associated with an established risk for QT prolongation and torsades de pointes (TdP). Clarithromycin should be used cautiously with other agents known to cause QT prolongation. Agents with potential to prolong the QT interval include: dolasetron.
Clofazimine: (Moderate) Concomitant use of clofazimine and dolasetron 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.
Clozapine: (Moderate) Administer dolasetron with caution in combination with clozapine as concurrent use may increase the risk of QT prolongation. Treatment with clozapine has been associated with QT prolongation, torsade de pointes (TdP), cardiac arrest, and sudden death. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram.
Cobicistat: (Moderate) The plasma concentrations of hydrodolasetron (primary dolasetron metabolite) may be elevated when dolasetron is administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as headache or cardiovascular effects, is recommended during coadministration. Cobicistat is a CYP3A4 and CYP2D6 inhibitor, while hydrodolasetron is a CYP3A4 and CYP2D6 substrate.
Codeine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering codeine with serotonin-receptor antagonists. The development of serotonin syndrome has been reported with 5-HT3 receptor antagonists, mostly when used in combination with other serotonergic medications. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Codeine; Guaifenesin: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering codeine with serotonin-receptor antagonists. The development of serotonin syndrome has been reported with 5-HT3 receptor antagonists, mostly when used in combination with other serotonergic medications. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Codeine; Guaifenesin; Pseudoephedrine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering codeine with serotonin-receptor antagonists. The development of serotonin syndrome has been reported with 5-HT3 receptor antagonists, mostly when used in combination with other serotonergic medications. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Codeine; Phenylephrine; Promethazine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering codeine with serotonin-receptor antagonists. The development of serotonin syndrome has been reported with 5-HT3 receptor antagonists, mostly when used in combination with other serotonergic medications. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. (Moderate) Concomitant use of promethazine and dolasetron 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) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering codeine with serotonin-receptor antagonists. The development of serotonin syndrome has been reported with 5-HT3 receptor antagonists, mostly when used in combination with other serotonergic medications. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. (Moderate) Concomitant use of promethazine and dolasetron 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.
Crizotinib: (Major) Avoid coadministration of crizotinib with dolasetron 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. Dolasetron has also been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram.
Darunavir: (Major) The plasma concentrations of hydrodolasetron (primary dolasetron metabolite) may be elevated when dolasetron is administered concurrently with darunavir. Clinical monitoring for adverse effects, such as headache or cardiovascular effects, is recommended during coadministration. Darunavir is a CYP3A4 and CYP2D6 inhibitor, while hydrodolasetron is a CYP3A4 and CYP2D6 substrate.
Darunavir; Cobicistat: (Major) The plasma concentrations of hydrodolasetron (primary dolasetron metabolite) may be elevated when dolasetron is administered concurrently with darunavir. Clinical monitoring for adverse effects, such as headache or cardiovascular effects, is recommended during coadministration. Darunavir is a CYP3A4 and CYP2D6 inhibitor, while hydrodolasetron is a CYP3A4 and CYP2D6 substrate. (Moderate) The plasma concentrations of hydrodolasetron (primary dolasetron metabolite) may be elevated when dolasetron is administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as headache or cardiovascular effects, is recommended during coadministration. Cobicistat is a CYP3A4 and CYP2D6 inhibitor, while hydrodolasetron is a CYP3A4 and CYP2D6 substrate.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Major) The plasma concentrations of hydrodolasetron (primary dolasetron metabolite) may be elevated when dolasetron is administered concurrently with darunavir. Clinical monitoring for adverse effects, such as headache or cardiovascular effects, is recommended during coadministration. Darunavir is a CYP3A4 and CYP2D6 inhibitor, while hydrodolasetron is a CYP3A4 and CYP2D6 substrate. (Moderate) The plasma concentrations of hydrodolasetron (primary dolasetron metabolite) may be elevated when dolasetron is administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as headache or cardiovascular effects, is recommended during coadministration. Cobicistat is a CYP3A4 and CYP2D6 inhibitor, while hydrodolasetron is a CYP3A4 and CYP2D6 substrate.
Dasatinib: (Moderate) Administer dolasetron with caution in combination with dasatinib as concurrent use may increase the risk of QT prolongation. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram. In vitro studies have shown that dasatinib has the potential to prolong the QT interval.
Degarelix: (Moderate) Consider whether the benefits of androgen deprivation therapy outweigh the potential risks in patients receiving dolasetron as concurrent use may increase the risk of QT prolongation. Androgen deprivation therapy (i.e., degarelix) may prolong the QT/QTc interval. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram.
Desflurane: (Major) Halogenated anesthetics should be used cautiously and with close monitoring with dolasetron. Halogenated anesthetics can prolong the QT interval. Dolasetron has been associated with a dose-dependant prolongation in the QT, PR, and QRS intervals on an electrocardiogram. Use of dolasetron injection for the prevention of chemotherapy-induced nausea and vomiting is contraindicated because the risk of QT prolongation is higher with the doses required for this indication; when the injection is used at lower doses (i.e., those approved for post-operative nausea and vomiting) or when the oral formulation is used, the risk of QT prolongation is lower and caution is advised.
Desvenlafaxine: (Major) Although clinical studies have shown that desvenlafaxine does not have a clinically relevant effect on CYP2D6 inhibition at doses of 100 mg/day, the manufacturer recommends that primary substrates of CYP2D6, such as dolasetron, be dosed at the original level when co-administered with desvenlafaxine 100 mg or lower or when desvenlafaxine is discontinued. The dose of these CYP2D6 substrates should be reduced by up to one-half if co-administered with desvenlafaxine 400 mg/day. In addition, because of the potential risk and severity of serotonin syndrome, use caution when administering these drugs together. If serotonin syndrome is suspected, discontinue dolasetron and concurrent serotonergic agents and initiate appropriate medical treatment. Serotonin syndrome has been reported when 5HT3 receptor antagonists have been used in combination with other serotonergic drugs. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death.
Deutetrabenazine: (Moderate) Administer dolasetron with caution in combination with deutetrabenazine due to risk of additive QT prolongation. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram. 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.
Dexmedetomidine: (Moderate) Concomitant use of dexmedetomidine and dolasetron 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: (Contraindicated) Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). Quinidine inhibits CYP2D6 and has QT-prolonging actions; quinidine is contraindicated with other drugs that prolong the QT interval and are metabolized by CYP2D6 as the effects on the QT interval may be increased during concurrent use of these agents. Drugs that prolong the QT and are substrates for CYP2D6 that are contraindicated with quinidine include dolasetron.
Digoxin: (Major) Dolasetron has been associated with a dose-dependant prolongation in the QT, PR, and QRS intervals on an electrocardiogram. Therefore, drugs known to prolong the PR interval, such as digoxin, should be avoided in patients taking dolasetron.
Diltiazem: (Major) Dolasetron has been associated with a dose-dependant prolongation in the QT, PR, and QRS intervals on an electrocardiogram. Therefore, drugs known to prolong the PR interval, such as diltiazem, should be avoided in patients taking dolasetron.
Disopyramide: (Major) Dolasetron should be used cautiously and with close monitoring with disopyramide. Disopyramide administration is associated with QT prolongation and torsades de pointes (TdP). Dolasetron has been associated with a dose-dependant prolongation in the QT, PR, and QRS intervals on an electrocardiogram. Use of dolasetron injection for the prevention of chemotherapy-induced nausea and vomiting is contraindicated because the risk of QT prolongation is higher with the doses required for this indication; when the injection is used at lower doses (i.e., those approved for post-operative nausea and vomiting) or when the oral formulation is used, the risk of QT prolongation is lower and caution is advised.
Dofetilide: (Major) Coadministration of dofetilide and dolasetron 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). Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram.
Dolutegravir; Rilpivirine: (Moderate) Administer dolasetron with caution in combination with rilpivirine. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram.
Donepezil: (Moderate) Use donepezil with caution in combination with dolasteron. Case reports indicate that QT prolongation and torsade de pointes (TdP) can occur during donepezil therapy. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram.
Donepezil; Memantine: (Moderate) Use donepezil with caution in combination with dolasteron. Case reports indicate that QT prolongation and torsade de pointes (TdP) can occur during donepezil therapy. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram.
Dronedarone: (Contraindicated) Concomitant use of dronedarone and dolasetron is contraindicated. Dronedarone is an inhibitor of CYP2D6 and CYP3A. Dolasetron is a substrate for CYP2D6 and CYP3A4. Coadministration of dronedarone and dolasetron may result in elevated plasma concentrations of dolasetron. In addition, dolasetron has been established to have a possible risk of QT prolongation and Torsade de Pointes (TdP). Dronedarone is associated with dose-related increases in the QTc interval. Dolasetron has also been associated with a dose-dependant prolongation in the PR interval on an electrocardiogram. 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; concomitant use is contraindicated.
Droperidol: (Major) Droperidol should not be used in combination with any drug known to have potential to prolong the QT interval, such as dolasetron. Droperidol administration is associated with an established risk for QT prolongation and torsade de pointes (TdP). Some cases have occurred in patients with no known risk factors for QT prolongation and some cases have been fatal. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram. If coadministration cannot be avoided, use extreme caution; initiate droperidol at a low dose and increase the dose as needed to achieve the desired effect.
Duloxetine: (Major) Because of the potential risk and severity of serotonin syndrome, use caution when administering dolasetron with other drugs that have serotonergic properties such as duloxetine. If serotonin syndrome is suspected, discontinue dolasetron and concurrent serotonergic agents and initiate appropriate medical treatment. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death.
Efavirenz: (Moderate) Consider alternatives to efavirenz when coadministering with dolasetron as concurrent use may increase the risk of QT prolongation. QTc prolongation has been observed with the use of efavirenz. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram.
Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Consider alternatives to efavirenz when coadministering with dolasetron as concurrent use may increase the risk of QT prolongation. QTc prolongation has been observed with the use of efavirenz. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram.
Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Moderate) Consider alternatives to efavirenz when coadministering with dolasetron as concurrent use may increase the risk of QT prolongation. QTc prolongation has been observed with the use of efavirenz. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram.
Elbasvir; Grazoprevir: (Minor) Administering dolasetron with grazoprevir may result in elevated dolasetron plasma concentrations. Dolasetron is a substrate of CYP3A; grazoprevir is a weak CYP3A inhibitor. If these drugs are used together, closely monitor for signs of adverse events.
Eliglustat: (Moderate) Administer dolasetron with caution in combination with eliglustat as concurrent use may increase the risk of QT prolongation. Eliglustat is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Moderate) The plasma concentrations of hydrodolasetron (primary dolasetron metabolite) may be elevated when dolasetron is administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as headache or cardiovascular effects, is recommended during coadministration. Cobicistat is a CYP3A4 and CYP2D6 inhibitor, while hydrodolasetron is a CYP3A4 and CYP2D6 substrate.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) The plasma concentrations of hydrodolasetron (primary dolasetron metabolite) may be elevated when dolasetron is administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as headache or cardiovascular effects, is recommended during coadministration. Cobicistat is a CYP3A4 and CYP2D6 inhibitor, while hydrodolasetron is a CYP3A4 and CYP2D6 substrate.
Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Moderate) Administer dolasetron with caution in combination with rilpivirine. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram.
Emtricitabine; Rilpivirine; Tenofovir Disoproxil Fumarate: (Moderate) Administer dolasetron with caution in combination with rilpivirine. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram.
Enalapril; Hydrochlorothiazide, HCTZ: (Moderate) Caution is advisable during concurrent use of dolasetron and thiazide diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with dolasetron.
Encorafenib: (Major) Avoid coadministration of encorafenib and dolasetron due to 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. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram.
Entrectinib: (Major) Avoid coadministration of entrectinib with dolasetron due to the risk of QT prolongation. Entrectinib has been associated with QT prolongation. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram.
Eprosartan; Hydrochlorothiazide, HCTZ: (Moderate) Caution is advisable during concurrent use of dolasetron and thiazide diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with dolasetron.
Eribulin: (Major) Dolasetron has been associated with a dose-dependant prolongation in the QT, PR, and QRS intervals on an electrocardiogram. Use of dolasetron injection for the prevention of chemotherapy-induced nausea and vomiting is contraindicated because the risk of QT prolongation is higher with the doses required for this indication; when the injection is used at lower doses (i.e., those approved for post-operative nausea and vomiting) or when the oral formulation is used, the risk of QT prolongation is lower and caution is advised. Drugs with a possible risk for QT prolongation and torsade de pointes (TdP) that should be used cautiously with dolasetron include eribulin. ECG monitoring is recommended; closely monitor the patient for QT interval prolongation.
Erythromycin: (Major) Due to a possible risk for QT prolongation and torsade de pointes (TdP), dolasetron and erythromycin should be used together cautiously. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram. Erythromycin is associated with QT prolongation and TdP. Concurrent use may increase the risk of QT prolongation.
Escitalopram: (Moderate) Concomitant use of escitalopram and dolasetron 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) Caution is advisable during concurrent use of dolasetron and loop diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with dolasetron.
Etrasimod: (Moderate) Concomitant use of etrasimod and dolasetron 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.
Fenfluramine: (Moderate) Monitor for decreased efficacy of fenfluramine if coadministered with serotonin receptor antagonists. Concurrent use may decrease the activity of fenfluramine. Also monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Fentanyl: (Major) Because of the potential risk and severity of serotonin syndrome, use caution when administering dolasetron with other drugs that have serotonergic properties such as fentanyl. If serotonin syndrome is suspected, discontinue dolasetron and concurrent serotonergic agents and initiate appropriate medical treatment. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death.
Fexinidazole: (Major) Concomitant use of fexinidazole and dolasetron 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) Administer dolasetron with caution in combination with fingolimod as concurrent use may increase the risk of QT prolongation. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram. 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.
Flecainide: (Major) Dolasetron should be used cautiously and with close monitoring with flecainide. Dolasetron has been associated with a dose-dependant prolongation in the QT, PR, and QRS intervals on an electrocardiogram. Dolasetron injection is contraindicated for use for the prevention of chemotherapy-induced nausea and vomiting because the risk of QT prolongation is higher with the doses used for this indication; when the injection is used at lower doses (i.e., those approved for post-operative nausea and vomiting) or when the oral formulation is used, the risk of QT prolongation is lower and caution is advised. Flecainide is a Class IC antiarrhythmic associated with a possible risk for QT prolongation and/or torsades de pointes (TdP); flecainide increases the QT interval, but largely due to prolongation of the QRS interval. Although causality for TdP has not been established for flecainide, patients receiving concurrent drugs which have the potential for QT prolongation may have an increased risk of developing proarrhythmias.
Fluconazole: (Moderate) Concomitant use of fluconazole and dolasetron 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.
Fluoxetine: (Moderate) Concomitant use of fluoxetine and dolasetron 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) Administer dolasetron with caution in combination with fluphenazine as concurrent use may increase the risk of QT prolongation. Fluphenazine is associated with a possible risk for QT prolongation. Theoretically, fluphenazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram.
Fluvoxamine: (Moderate) Administer dolasetron with caution in combination with fluvoxamine as concurrent use may increase the risk of QT prolongation; the risk of serotonin syndrome may also increase. QT prolongation and torsade de pointes (TdP) have been reported during fluvoxamine post-marketing use. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram. If serotonin syndrome occurs, discontinue all serotonergic agents and initiate appropriate medical treatment.
Foscarnet: (Major) When possible, avoid concurrent use of foscarnet with other drugs known to prolong the QT interval, such as dolasetron. Foscarnet has been associated with postmarketing reports of both QT prolongation and torsade de pointes (TdP). Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram. If these drugs are administered together, obtain an electrocardiogram and electrolyte concentrations before and periodically during treatment.
Fosinopril; Hydrochlorothiazide, HCTZ: (Moderate) Caution is advisable during concurrent use of dolasetron and thiazide diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with dolasetron.
Fostemsavir: (Moderate) Administer dolasetron with caution in combination with fostemsavir. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram. Supratherapeutic doses of fostemsavir (2,400 mg twice daily, 4 times the recommended daily dose) have been shown to cause QT prolongation. Fostemsavir causes dose-dependent QT prolongation.
Furosemide: (Moderate) Caution is advisable during concurrent use of dolasetron and loop diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with dolasetron.
Gemifloxacin: (Moderate) Administer dolasetron with caution in combination with gemifloxacin as concurrent use may increase the risk of QT prolongation. Gemifloxacin may prolong the QT interval in some patients. The maximal change in the QTc interval occurs approximately 5 to 10 hours following oral administration of gemifloxacin. The likelihood of QTc prolongation may increase with increasing dose of the drug; therefore, the recommended dose should not be exceeded especially in patients with renal or hepatic impairment where the Cmax and AUC are slightly higher. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram.
Gemtuzumab Ozogamicin: (Moderate) Administer dolasetron with caution in combination with gemtuzumab as concurrent use may increase the risk of QT prolongation. 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. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram.
Gilteritinib: (Moderate) Use caution and monitor for evidence of QT prolongation if concurrent use of gilteritinib and dolasetron is necessary. Gilteritinib has been associated with QT prolongation. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram. Coadministration has the potential for additive QT prolongation.
Glasdegib: (Major) Avoid coadministration of glasdegib with dolasetron 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. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram.
Goserelin: (Moderate) Consider whether the benefits of androgen deprivation therapy outweigh the potential risks in patients receiving dolasetron as concurrent use may increase the risk of QT prolongation. Androgen deprivation therapy (i.e., goserelin) may prolong the QT/QTc interval. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram.
Granisetron: (Moderate) Administer dolasetron with caution in combination with granisetron. Granisetron has been associated with QT prolongation. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram. Because both dolasetron and granisetron have serotonergic properties, serotonin syndrome is possible. Serotonin syndrome is characterized by the rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. If serotonin syndrome occurs, discontinue all serotonergic agents and initiate appropriate medical treatment.
Halogenated Anesthetics: (Major) Halogenated anesthetics should be used cautiously and with close monitoring with dolasetron. Halogenated anesthetics can prolong the QT interval. Dolasetron has been associated with a dose-dependant prolongation in the QT, PR, and QRS intervals on an electrocardiogram. Use of dolasetron injection for the prevention of chemotherapy-induced nausea and vomiting is contraindicated because the risk of QT prolongation is higher with the doses required for this indication; when the injection is used at lower doses (i.e., those approved for post-operative nausea and vomiting) or when the oral formulation is used, the risk of QT prolongation is lower and caution is advised.
Haloperidol: (Moderate) Administer dolasetron with caution in combination with haloperidol 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. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram.
Histrelin: (Moderate) Consider whether the benefits of androgen deprivation therapy outweigh the potential risks in patients receiving dolasetron as concurrent use may increase the risk of QT prolongation. Androgen deprivation therapy (i.e., histrelin) may prolong the QT/QTc interval. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram.
Homatropine; Hydrocodone: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering hydrocodone with serotonin-receptor antagonists. The development of serotonin syndrome has been reported with 5-HT3 receptor antagonists, mostly when used in combination with other serotonergic medications. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Hydrochlorothiazide, HCTZ: (Moderate) Caution is advisable during concurrent use of dolasetron and thiazide diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with dolasetron.
Hydrochlorothiazide, HCTZ; Moexipril: (Moderate) Caution is advisable during concurrent use of dolasetron and thiazide diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with dolasetron.
Hydrocodone: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering hydrocodone with serotonin-receptor antagonists. The development of serotonin syndrome has been reported with 5-HT3 receptor antagonists, mostly when used in combination with other serotonergic medications. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Hydrocodone; Ibuprofen: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering hydrocodone with serotonin-receptor antagonists. The development of serotonin syndrome has been reported with 5-HT3 receptor antagonists, mostly when used in combination with other serotonergic medications. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Hydromorphone: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering hydromorphone with serotonin-receptor antagonists. The development of serotonin syndrome has been reported with 5-HT3 receptor antagonists, mostly when used in combination with other serotonergic medications. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Hydroxychloroquine: (Major) Avoid coadministration of dolasetron and hydroxychloroquine due to the risk of increased 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. Hydroxychloroquine prolongs the QT interval. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram.
Hydroxyzine: (Moderate) Concomitant use of hydroxyzine and dolasetron 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.
Hyoscyamine; Methenamine; Methylene Blue; Phenyl Salicylate; Sodium Biphosphate: (Major) Because of the potential risk and severity of serotonin syndrome, use caution when administering dolasetron with other drugs that have serotonergic properties such as methylene blue. If serotonin syndrome is suspected, discontinue dolasetron and concurrent serotonergic agents and initiate appropriate medical treatment. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death.
Ibuprofen; Oxycodone: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering oxycodone with serotonin-receptor antagonists. The development of serotonin syndrome has been reported with 5-HT3 receptor antagonists, mostly when used in combination with other serotonergic medications. Inform patients taking this combination of the possible increased risks and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Ibutilide: (Major) Use caution during concurrent use of dolasetron and ibutilide. Dolasetron has been associated with a dose-dependant prolongation in the QT, PR, and QRS intervals on an electrocardiogram. Use of dolasetron injection for the prevention of chemotherapy-induced nausea and vomiting is contraindicated because the risk of QT prolongation is higher with the doses required for this indication; when the injection is used at lower doses (i.e., those approved for post-operative nausea and vomiting) or when the oral formulation is used, the risk of QT prolongation is lower and caution is advised. 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.
Idelalisib: (Major) Avoid concomitant use of idelalisib, a strong CYP3A inhibitor, with dolasetron, a CYP3A substrate, as dolasetron toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Iloperidone: (Major) Due to a possible risk for QT prolongation and torsade de pointes (TdP), dolasetron and iloperidone should be used together cautiously. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram. Iloperidone has been associated with QT prolongation. 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.
Inotuzumab Ozogamicin: (Major) Avoid coadministration of inotuzumab ozogamicin with dolasetron due to the potential for additive QT interval 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. Inotuzumab has been associated with QT interval prolongation. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an ECG.
Ipecac: (Major) Ipecac has been shown to be effective in producing emesis in patients who have ingested antiemetics, provided ipecac is given promptly (usually within 1 hour of antiemetic consumption). If ipecac is administered after the antiemetic therapy has begun to exert therapeutic effects, ipecac may be less effective. The duration of the antiemetics action may need to be taken into account when selecting the appropriate clinical path for treating patients for overdosage. Patients on chronic or longer-acting antiemetic therapy, such as the 5HT-3 receptor antagonists, may be unresponsive to ipecac or other methods which induce vomiting.
Irbesartan; Hydrochlorothiazide, HCTZ: (Moderate) Caution is advisable during concurrent use of dolasetron and thiazide diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with dolasetron.
Isavuconazonium: (Moderate) Concomitant use of isavuconazonium with dolasetron may result in increased serum concentrations of dolasetron. Dolasetron is a substrate of the hepatic isoenzyme CYP3A4; isavuconazole, the active moiety of isavuconazonium, is a moderate inhibitor of this enzyme. Caution and close monitoring are advised if these drugs are used together.
Isocarboxazid: (Moderate) Because of the potential risk and severity of serotonin syndrome, use caution when administering dolasetron with other drugs that have serotonergic properties such as monoamine oxidase inhibitors (MAOIs). Serotonin syndrome has been described following the concomitant use of 5-HT3 receptor antagonists and other serotonergic drugs. Monitor for the emergence of serotonin syndrome. If serotonin syndrome is suspected, discontinue dolasetron and concurrent serotonergic agents and initiate appropriate medical treatment.
Isoflurane: (Major) Halogenated anesthetics should be used cautiously and with close monitoring with dolasetron. Halogenated anesthetics can prolong the QT interval. Dolasetron has been associated with a dose-dependant prolongation in the QT, PR, and QRS intervals on an electrocardiogram. Use of dolasetron injection for the prevention of chemotherapy-induced nausea and vomiting is contraindicated because the risk of QT prolongation is higher with the doses required for this indication; when the injection is used at lower doses (i.e., those approved for post-operative nausea and vomiting) or when the oral formulation is used, the risk of QT prolongation is lower and caution is advised.
Isoniazid, INH; Pyrazinamide, PZA; Rifampin: (Moderate) Blood concentrations of hydrodolasetron, the active metabolite of dolasetron, may be decreased when dolasetron is administered concomitantly with rifampin, a potent inducer of cytochrome P450.
Isoniazid, INH; Rifampin: (Moderate) Blood concentrations of hydrodolasetron, the active metabolite of dolasetron, may be decreased when dolasetron is administered concomitantly with rifampin, a potent inducer of cytochrome P450.
Itraconazole: (Moderate) Administer dolasetron with caution in combination with itraconazole as concurrent use may increase the risk of QT prolongation. Itraconazole has been associated with prolongation of the QT interval. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram.
Ivosidenib: (Major) Avoid coadministration of ivosidenib with dolasetron 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. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram.
Ketoconazole: (Contraindicated) Avoid concomitant use of ketoconazole and dolasetron due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
Lansoprazole; Amoxicillin; Clarithromycin: (Contraindicated) Clarithromycin is associated with an established risk for QT prolongation and torsades de pointes (TdP). Clarithromycin should be used cautiously with other agents known to cause QT prolongation. Agents with potential to prolong the QT interval include: dolasetron.
Lapatinib: (Moderate) Administer dolasetron with caution in combination with lapatinib as concurrent use may increase the risk of QT prolongation. Lapatinib has been associated with concentration-dependent QT prolongation; ventricular arrhythmias and torsade de pointes (TdP) have been reported in postmarketing experience. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram.
Lasmiditan: (Moderate) Serotonin syndrome may occur during coadministration of lasmiditan and serotonin-receptor antagonists. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome, particularly after a dose increase or the addition of other serotonergic medications to an existing regimen. Discontinue all serotonergic agents if serotonin syndrome occurs and implement appropriate medical management.
Lefamulin: (Major) Avoid coadministration of lefamulin with dolasetron 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. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram.
Lenvatinib: (Major) Avoid coadministration of lenvatinib with dolasetron due to the risk of QT prolongation. Prolongation of the QT interval has been reported with lenvatinib therapy. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram.
Leuprolide: (Moderate) Consider whether the benefits of androgen deprivation therapy outweigh the potential risks in patients receiving dolasetron as concurrent use may increase the risk of QT prolongation. Androgen deprivation therapy (i.e., leuprolide) may prolong the QT/QTc interval. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram.
Leuprolide; Norethindrone: (Moderate) Consider whether the benefits of androgen deprivation therapy outweigh the potential risks in patients receiving dolasetron as concurrent use may increase the risk of QT prolongation. Androgen deprivation therapy (i.e., leuprolide) may prolong the QT/QTc interval. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram.
Levofloxacin: (Moderate) Concomitant use of levofloxacin and dolasetron 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 dolasetron due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
Levomilnacipran: (Major) Because of the potential risk and severity of serotonin syndrome, use caution when administering dolasetron with other drugs that have serotonergic properties such as levomilnacipran. If serotonin syndrome is suspected, discontinue dolasetron and concurrent serotonergic agents and initiate appropriate medical treatment. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death.
Levorphanol: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering levorphanol with serotonin-receptor antagonists. The development of serotonin syndrome has been reported with 5-HT3 receptor antagonists, mostly when used in combination with other serotonergic medications. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Linezolid: (Major) Because of the potential risk and severity of serotonin syndrome, use caution when administering dolasetron with other drugs that have serotonergic properties such as linezolid. If serotonin syndrome is suspected, discontinue dolasetron and concurrent serotonergic agents and initiate appropriate medical treatment. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death.
Lisinopril; Hydrochlorothiazide, HCTZ: (Moderate) Caution is advisable during concurrent use of dolasetron and thiazide diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with dolasetron.
Lithium: (Moderate) Administer dolasetron with caution in combination with lithium as concurrent use may increase the risk of QT prolongation; the risk of serotonin syndrome may also increase. Lithium has been associated with QT prolongation. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram. If serotonin syndrome occurs, discontinue all serotonergic agents and initiate appropriate medical treatment.
Lofexidine: (Major) Monitor ECG if lofexidine is coadministered with dolasetron due to the potential for additive QT prolongation. Lofexidine prolongs the QT interval. In addition, there are postmarketing reports of torsade de pointes. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals.
Loop diuretics: (Moderate) Caution is advisable during concurrent use of dolasetron and loop diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with dolasetron.
Loperamide: (Moderate) Administer dolasetron with caution in combination with loperamide as concurrent use may increase the risk of QT prolongation. At high doses, loperamide has been associated with serious cardiac toxicities, including syncope, ventricular tachycardia, QT prolongation, torsade de pointes (TdP), and cardiac arrest. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram.
Loperamide; Simethicone: (Moderate) Administer dolasetron with caution in combination with loperamide as concurrent use may increase the risk of QT prolongation. At high doses, loperamide has been associated with serious cardiac toxicities, including syncope, ventricular tachycardia, QT prolongation, torsade de pointes (TdP), and cardiac arrest. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram.
Lopinavir; Ritonavir: (Major) Avoid coadministration of lopinavir with dolasetron 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. Lopinavir is associated with QT prolongation. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram.
Losartan; Hydrochlorothiazide, HCTZ: (Moderate) Caution is advisable during concurrent use of dolasetron and thiazide diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with dolasetron.
Lumacaftor; Ivacaftor: (Minor) Lumacaftor; ivacaftor may reduce the efficacy of dolasetron by decreasing its systemic exposure. Dolasetron is partially metabolized by CYP3A4. Lumacaftor is a strong inducer of CYP3A. When oral dolasetron was administered with rifampin, another strong CYP3A inducer, for 7 days, the AUC and Cmax of hydrodolasetron decreased by 28% and 17%, respectively. Of note, rifampin is also a weak inducer of CYP2D6, the primary substrate of dolasetron, but lumacaftor; ivacaftor does not affect CYP2D6.
Lumacaftor; Ivacaftor: (Minor) Lumacaftor; ivacaftor may reduce the efficacy of dolasetron by decreasing its systemic exposure. Dolasetron is partially metabolized by CYP3A4. Lumacaftor is a strong inducer of CYP3A. When oral dolasetron was administered with rifampin, another strong CYP3A inducer, for 7 days, the AUC and Cmax of hydrodolasetron decreased by 28% and 17%, respectively. Of note, rifampin is also a weak inducer of CYP2D6, the primary substrate of dolasetron, but lumacaftor; ivacaftor does not affect CYP2D6.
Macimorelin: (Major) Avoid concurrent administration of macimorelin with drugs that prolong the QT interval, such as dolasetron. 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. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram.
Maprotiline: (Moderate) Administer dolasetron with caution in combination with maprotiline as concurrent use may increase the risk of QT prolongation. 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. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram.
Mefloquine: (Moderate) Administer dolasetron with caution in combination with mefloquine 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. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram.
Meperidine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering meperidine with serotonin-receptor antagonists. The development of serotonin syndrome has been reported with 5-HT3 receptor antagonists, mostly when used in combination with other serotonergic medications. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Metaxalone: (Moderate) Concomitant use of metaxalone and serotonin-receptor antagonists (5HT-3 receptor antagonists) may increase the risk for serotonin syndrome. Monitor patients for serotonin syndrome if concomitant use is necessary.
Methadone: (Major) Due to a possible risk for QT prolongation and torsade de pointes (TdP), dolasetron and methadone should be used together cautiously. Dolasetron has been associated with a dose-dependant prolongation in the QT, PR, and QRS intervals on an electrocardiogram. Use of dolasetron injection for the prevention of chemotherapy-induced nausea and vomiting is contraindicated because the risk of QT prolongation is higher with the doses required for this indication; when the injection is used at lower doses (i.e., those approved for post-operative nausea and vomiting) or when the oral formulation is used, the risk of QT prolongation is lower and caution is advised. he 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.
Methenamine; Sodium Acid Phosphate; Methylene Blue; Hyoscyamine: (Major) Because of the potential risk and severity of serotonin syndrome, use caution when administering dolasetron with other drugs that have serotonergic properties such as methylene blue. If serotonin syndrome is suspected, discontinue dolasetron and concurrent serotonergic agents and initiate appropriate medical treatment. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death.
Methylene Blue: (Major) Because of the potential risk and severity of serotonin syndrome, use caution when administering dolasetron with other drugs that have serotonergic properties such as methylene blue. If serotonin syndrome is suspected, discontinue dolasetron and concurrent serotonergic agents and initiate appropriate medical treatment. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death.
Metolazone: (Moderate) Caution is advisable during concurrent use of dolasetron and thiazide diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with dolasetron.
Metoprolol; Hydrochlorothiazide, HCTZ: (Moderate) Caution is advisable during concurrent use of dolasetron and thiazide diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with dolasetron.
Metronidazole: (Moderate) Concomitant use of metronidazole and dolasetron 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 dolasetron may lead to additive QT interval prolongation. If these drugs are used together, consider obtaining electrocardiograms (ECG) to monitor the QT interval. Monitor electrolytes prior to and during dolasetron therapy and correct electrolyte abnormalities before starting therapy. ECG monitoring is recommended in elderly patients and patients with congestive heart failure, bradycardia, or renal impairment. In clinical trials, QT prolongation has been reported in patients who received midostaurin as single-agent therapy or in combination with cytarabine and daunorubicin. Dolasetron may cause dose-dependent ECG interval changes including PR and QTc prolongation and QRS widening. Ventricular tachycardia, ventricular fibrillation, and torsade de pointes have been reported following IV administration of dolasetron in post-marketing surveillance.
Mifepristone: (Major) Concomitant use of dolasetron and mifepristone 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.
Mirabegron: (Moderate) Mirabegron is a moderate CYP2D6 inhibitor. Exposure of drugs metabolized by CYP2D6 isoenzymes such as dolasetron may be increased when co-administered with mirabegron. Dolasetron is primarily metabolized by CYP2D6. Therefore, appropriate monitoring and dose adjustment may be necessary.
Mirtazapine: (Moderate) Administer dolasetron with caution in combination with mirtazapine as concurrent use may increase the risk of QT prolongation; the risk of serotonin syndrome may also increase. Mirtazapine has been associated with dose-dependent prolongation of the QT interval. Torsade de pointes (TdP) has been reported postmarketing, primarily in overdose or in patients with other risk factors for QT prolongation. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram. If serotonin syndrome occurs, discontinue all serotonergic agents and initiate appropriate medical treatment.
Mitotane: (Moderate) Use caution if mitotane and dolasetron are used concomitantly, and monitor for decreased efficacy of dolasetron and a possible change in dosage requirements. Mitotane is a strong CYP3A4 inducer and dolasetron is a CYP3A4 substrate; coadministration may result in decreased plasma concentrations of dolasetron. When oral dolasetron was administered with rifampin, another strong CYP3A inducer, for 7 days, the AUC and Cmax of hydrodolasetron decreased by 28% and 17%, respectively.
Mobocertinib: (Major) Concomitant use of mobocertinib and dolasetron 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.
Monoamine oxidase inhibitors: (Moderate) Because of the potential risk and severity of serotonin syndrome, use caution when administering dolasetron with other drugs that have serotonergic properties such as monoamine oxidase inhibitors (MAOIs). Serotonin syndrome has been described following the concomitant use of 5-HT3 receptor antagonists and other serotonergic drugs. Monitor for the emergence of serotonin syndrome. If serotonin syndrome is suspected, discontinue dolasetron and concurrent serotonergic agents and initiate appropriate medical treatment.
Morphine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering morphine with serotonin-receptor antagonist. The development of serotonin syndrome has been reported with 5-HT3 receptor antagonists, mostly when used in combination with other serotonergic medications. Inform patients taking this combination of the possible increased risks and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Morphine; Naltrexone: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering morphine with serotonin-receptor antagonist. The development of serotonin syndrome has been reported with 5-HT3 receptor antagonists, mostly when used in combination with other serotonergic medications. Inform patients taking this combination of the possible increased risks and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Moxifloxacin: (Major) Due to a possible risk for QT prolongation and torsade de pointes (TdP), dolasetron and moxifloxacin should be used together cautiously. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram. Quinolones have been associated with a risk of QT prolongation and TdP. Although extremely rare, TdP has been reported during postmarketing surveillance of moxifloxacin. These reports generally involved patients with concurrent medical conditions or concomitant medications that may have been contributory. Moxifloxacin should be used cautiously with other agents that may prolong the QT interval or increase the risk of TdP.
Nalbuphine: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering nalbuphine with serotonin-receptor antagonists. The development of serotonin syndrome has been reported with 5-HT3 receptor antagonists, mostly when used in combination with other serotonergic medications. Inform patients taking this combination of the possible increased risks and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Nilotinib: (Major) Avoid the concomitant use of nilotinib with other agents that prolong the QT interval, such as dolasetron. Sudden death and QT interval prolongation have occurred in patients who received nilotinib therapy. Dolasetron has also been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals. Concomitant use may increase the risk for QT prolongation.
Ofloxacin: (Moderate) Concomitant use of ofloxacin and dolasetron 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) Administer dolasetron with caution in combination with olanzapine as concurrent use may increase the risk of QT prolongation. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram.
Olanzapine; Fluoxetine: (Moderate) Administer dolasetron with caution in combination with olanzapine as concurrent use may increase the risk of QT prolongation. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram. (Moderate) Concomitant use of fluoxetine and dolasetron 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; Samidorphan: (Moderate) Administer dolasetron with caution in combination with olanzapine as concurrent use may increase the risk of QT prolongation. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram.
Oliceridine: (Moderate) If concomitant use of oliceridine and serotonin-receptor antagonists is warranted, monitor patients for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. The concomitant use of opioids with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome.
Olmesartan; Amlodipine; Hydrochlorothiazide, HCTZ: (Moderate) Caution is advisable during concurrent use of dolasetron and thiazide diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with dolasetron.
Olmesartan; Hydrochlorothiazide, HCTZ: (Moderate) Caution is advisable during concurrent use of dolasetron and thiazide diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with dolasetron.
Ondansetron: (Major) These drugs would not be expected to be given together due to therapeutic class duplication; side effects, such as serotonergic actions, may be additive. Ondansetron has been associated with QT prolongation and post-marketing reports of torsade de pointes (TdP). If ondansetron and another drug that prolongs the QT interval must be coadministered, ECG monitoring is recommended. Dolasetron is associated with a lower, but possible risk for QT prolongation and TdP.
Oritavancin: (Minor) Dolasetron is metabolized by CYP3A4 and CYP2D6; oritavancin is a weak CYP3A4 and CYP2D6 inducer. Plasma concentrations and efficacy of dolasetron may be reduced if these drugs are administered concurrently.
Osilodrostat: (Moderate) Monitor ECGs in patients receiving osilodrostat with dolasetron. Osilodrostat is associated with dose-dependent QT prolongation. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram.
Osimertinib: (Major) Avoid coadministration of dolasetron 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. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram.
Oxaliplatin: (Major) Monitor ECGs and electrolytes in patients receiving oxaliplatin and dolasetron concomitantly; correct electrolyte abnormalities prior to administration of oxaliplatin. QT prolongation and ventricular arrhythmias including fatal torsade de pointes have been reported with oxaliplatin use in postmarketing experience. Dolasetron has also been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram.
Oxycodone: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering oxycodone with serotonin-receptor antagonists. The development of serotonin syndrome has been reported with 5-HT3 receptor antagonists, mostly when used in combination with other serotonergic medications. Inform patients taking this combination of the possible increased risks and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Oxymorphone: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering oxymorphone with serotonin-receptor antagonists. The development of serotonin syndrome has been reported with 5-HT3 receptor antagonists, mostly when used in combination with other serotonergic medications. Inform patients taking this combination of the possible increased risks and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Ozanimod: (Major) In general, do not initiate ozanimod in patients taking dolasetron due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). Additionally, there is a potential for hypertensive crisis. If treatment initiation is considered, seek advice from a cardiologist and monitor for hypertension. An active metabolite of ozanimod inhibits MAO-B, which may increase the potential for hypertensive crisis. Ozanimod may also 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. Dolasetron is a serotonergic drug that has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram.
Pacritinib: (Major) Concomitant use of pacritinib and dolasetron 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) Avoid coadministration of paliperidone and dolasetron if possible due to a possible increased risk for QT prolongation and torsade de pointes (TdP). If coadministration is necessary and the patient has known risk factors for cardiac disease or arrhythmias, close monitoring is essential. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram. Paliperidone has been associated with QT prolongation; torsade de pointes (TdP) and ventricular fibrillation have been reported in the setting of overdose.
Panobinostat: (Major) The co-administration of panobinostat with antiemetic agents such as dolasetron may increase the risk of QT prolongation. If concomitant use cannot be avoided, obtain electrocardiograms frequently and closely monitor patients for signs and symptoms of dolasetron toxicity, including QT prolongation and cardiac arrhythmias. Panobinostat is a CYP2D6 inhibitor and dolasetron is a CYP2D6 substrate. When a single-dose of a CYP2D6-sensitive substrate was administered after 3 doses of panobinostat (20 mg given on days 3, 5, and 8), the CYP2D6 substrate Cmax increased by 20% to 200% and the AUC value increased by 20% to 130% in 14 patients with advanced cancer; exposure was highly variable (coefficient of variance > 150%).
Paroxetine: (Major) Because of the potential risk and severity of serotonin syndrome, use caution when administering dolasetron with other drugs that have serotonergic properties such as paroxetine. Serotonin syndrome is characterized by the rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death. If serotonin syndrome is suspected, discontinue dolasetron and concurrent serotonergic agents and initiate appropriate medical treatment. In addition, because dolasetron is a CYP2D6 substrate and has a possible risk of QT prolongation and torsade de pointes, concurrent use of a potent CYP2D6 inhibitor such as paroxetine may increase the risk of such events.
Pasireotide: (Moderate) Administer dolasetron with caution in combination with pasireotide as concurrent use may increase the risk of QT prolongation. QT prolongation has occurred with pasireotide at therapeutic and supra-therapeutic doses. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram.
Pazopanib: (Major) Due to a possible risk for QT prolongation and torsade de pointes (TdP), dolasetron and pazopanib should be used together cautiously. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram. Coadministration of pazopanib and other drugs that prolong the QT interval is not advised; pazopanib has also been reported to prolong the QT interval.
Peginterferon Alfa-2b: (Moderate) Monitor for adverse effects associated with increased exposure to dolasetron if peginterferon alfa-2b is coadministered. Peginterferon alfa-2b is a CYP2D6 inhibitor, while dolasetron is a CYP2D6 substrate.
Pentamidine: (Major) Due to a possible risk for QT prolongation and torsade de pointes (TdP), dolasetron and pentamidine should be used together cautiously. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram. Systemic pentamidine has also been associated with QT prolongation. Concurrent use may increase the risk of QT prolongation.
Perphenazine: (Minor) Due to a possible risk for QT prolongation and torsade de pointes (TdP), dolasetron and perphenazine should be used together cautiously. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram. Perphenazine, a phenothiazine, is also associated with a possible risk for QT prolongation.
Perphenazine; Amitriptyline: (Minor) Due to a possible risk for QT prolongation and torsade de pointes (TdP), dolasetron and perphenazine should be used together cautiously. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram. Perphenazine, a phenothiazine, is also associated with a possible risk for QT prolongation.
Phenelzine: (Moderate) Because of the potential risk and severity of serotonin syndrome, use caution when administering dolasetron with other drugs that have serotonergic properties such as monoamine oxidase inhibitors (MAOIs). Serotonin syndrome has been described following the concomitant use of 5-HT3 receptor antagonists and other serotonergic drugs. Monitor for the emergence of serotonin syndrome. If serotonin syndrome is suspected, discontinue dolasetron and concurrent serotonergic agents and initiate appropriate medical treatment.
Pimavanserin: (Major) Pimavanserin may cause QT prolongation and should generally be avoided in patients receiving other medications known to prolong the QT interval, such as dolasetron. Dolasetron has been associated with a dose-dependant prolongation in the QT, PR, and QRS intervals on an electrocardiogram. Use of dolasetron injection for the prevention of chemotherapy-induced nausea and vomiting is contraindicated because the risk of QT prolongation is higher with the doses required for this indication; when the injection is used at lower doses (i.e., those approved for post-operative nausea and vomiting) or when the oral formulation is used, the risk of QT prolongation is lower. 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 dolasetron with pimozide is contraindicated.
Pitolisant: (Major) Avoid coadministration of pitolisant with dolasetron as concurrent use may increase the risk of QT prolongation. Pitolisant prolongs the QT interval. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram.
Ponesimod: (Major) In general, do not initiate ponesimod in patients taking dolasetron due to the risk of additive bradycardia, QT prolongation, and torsade de pointes (TdP). If treatment initiation is considered, seek advice from a cardiologist. 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. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram.
Posaconazole: (Moderate) Administer dolasetron with caution in combination with posaconazole. Posaconazole has been associated with prolongation of the QT interval as well as rare cases of torsade de pointes. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram.
Primaquine: (Moderate) Administer dolasetron with caution in combination with primaquine as concurrent use may increase the risk of QT prolongation. Primaquine has the potential for QT prolongation. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram.
Procainamide: (Major) Dolasetron should be used cautiously with procainamide. Procainamide is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Dolasetron has been associated with a dose-dependant prolongation in the QT, PR, and QRS intervals on an electrocardiogram. Use of dolasetron injection for the prevention of chemotherapy-induced nausea and vomiting is contraindicated because the risk of QT prolongation is higher with the doses required for this indication; when the injection is used at lower doses (i.e., those approved for post-operative nausea and vomiting) or when the oral formulation is used, the risk of QT prolongation is lower and caution is advised.
Prochlorperazine: (Minor) Administer dolasetron with caution in combination with prochlorperazine. Prochlorperazine is associated with a possible risk for QT prolongation. Theoretically, prochlorperazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram.
Promethazine: (Moderate) Concomitant use of promethazine and dolasetron 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 dolasetron 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 dolasetron 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 propafenone and dolasetron 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 quetiapine and dolasetron 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) Caution is advisable during concurrent use of dolasetron and thiazide diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with dolasetron.
Quinidine: (Contraindicated) Quinidine administration is associated with QT prolongation and torsades de pointes (TdP). Quinidine inhibits CYP2D6 and has QT-prolonging actions; quinidine is contraindicated with other drugs that prolong the QT interval and are metabolized by CYP2D6 as the effects on the QT interval may be increased during concurrent use of these agents. Drugs that prolong the QT and are substrates for CYP2D6 that are contraindicated with quinidine include dolasetron.
Quinine: (Major) Concurrent use of quinine and dolasetron 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. Dolasetron has also been associated with a dose-dependant prolongation in the QT, PR, and QRS intervals on an electrocardiogram. Use of dolasetron injection for the prevention of chemotherapy-induced nausea and vomiting is contraindicated because the risk of QT prolongation is higher with the doses required for this indication; when the injection is used at lower doses (i.e., those approved for post-operative nausea and vomiting) or when the oral formulation is used, the risk of QT prolongation is lower and caution is advised. In addition, concentrations of dolasetron may be increased with concomitant use of quinine. Dolasetron is a CYP3A4 and CYP2D6 substrate and quinine is an inhibitor of both enzymes.
Quizartinib: (Major) Concomitant use of quizartinib and dolasetron 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) Administer dolasetron with caution in combination with ranolazine. 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. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram.
Relugolix: (Moderate) Administer dolasetron with caution in combination with relugolix. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval.
Relugolix; Estradiol; Norethindrone acetate: (Moderate) Administer dolasetron with caution in combination with relugolix. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval.
Remifentanil: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering remifentanil with serotonin-receptor antagonists. Inform patients taking this combination of the possible increased risks and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Ribociclib: (Major) Avoid coadministration of ribociclib with dolasetron due to an increased risk for QT prolongation. Ribociclib has been shown to prolong the QT interval in a concentration-dependent manner. Dolasetron has also been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals. Concomitant use may increase the risk for QT prolongation.
Ribociclib; Letrozole: (Major) Avoid coadministration of ribociclib with dolasetron due to an increased risk for QT prolongation. Ribociclib has been shown to prolong the QT interval in a concentration-dependent manner. Dolasetron has also been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals. Concomitant use may increase the risk for QT prolongation.
Rifampin: (Moderate) Blood concentrations of hydrodolasetron, the active metabolite of dolasetron, may be decreased when dolasetron is administered concomitantly with rifampin, a potent inducer of cytochrome P450.
Rilpivirine: (Moderate) Administer dolasetron with caution in combination with rilpivirine. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram.
Risperidone: (Moderate) Administer dolasetron with caution in combination with risperidone. Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram.
Romidepsin: (Moderate) Consider monitoring electrolytes and ECGs at baseline and periodically during treatment if romidepsin is administered with dolasetron. Romidepsin has been reported to prolong the QT interval. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram.
Saquinavir: (Contraindicated) Concurrent use of saquinavir boosted with ritonavir and dolasetron should be avoided if possible due to the risk of life threatening arrhythmias such as torsade de pointes (TdP). Saquinavir boosted with ritonavir causes dose-dependent QT and PR prolongation; if possible, avoid use with other drugs that may prolong the QT or PR interval, such as dolasetron. If no alternative therapy is acceptable, perform a baseline ECG prior to initiation of concomitant therapy and follow recommended ECG monitoring.
Selegiline: (Moderate) Monitor for signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increase, during concomitant selegiline and serotonin-receptor antagonist use. If serotonin syndrome occurs, discontinue therapy. Concomitant use increases the risk for serotonin syndrome.
Selpercatinib: (Major) Monitor ECGs more frequently for QT prolongation if coadministration of selpercatinib with dolasetron is necessary due to the risk of additive QT prolongation. Concentration-dependent QT prolongation has been observed with selpercatinib therapy. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram.
Sertraline: (Moderate) Use caution and monitor patients for QT prolongation and serotonin syndrome when administering dolasetron with sertraline. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram. Sertraline's FDA-approved labeling recommends avoiding concomitant use with drugs known to prolong the QTc interval; however, the risk of sertraline-induced QT prolongation is generally considered to be low in clinical practice. Its effect on QTc interval is minimal (typically less than 5 msec), and the drug has been used safely in patients with cardiac disease (e.g., recent myocardial infarction, unstable angina, chronic heart failure). In addition, taking these drugs together may increase the risk for serotonin syndrome. If concurrent use is required and serotonin syndrome occurs, discontinue all serotonergic agents and initiate appropriate medical treatment.
Sevoflurane: (Major) Halogenated anesthetics should be used cautiously and with close monitoring with dolasetron. Halogenated anesthetics can prolong the QT interval. Dolasetron has been associated with a dose-dependant prolongation in the QT, PR, and QRS intervals on an electrocardiogram. Use of dolasetron injection for the prevention of chemotherapy-induced nausea and vomiting is contraindicated because the risk of QT prolongation is higher with the doses required for this indication; when the injection is used at lower doses (i.e., those approved for post-operative nausea and vomiting) or when the oral formulation is used, the risk of QT prolongation is lower and caution is advised.
Siponimod: (Major) In general, do not initiate treatment with siponimod in patients receiving dolasetron 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. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram.
Sodium Stibogluconate: (Moderate) Concomitant use of sodium stibogluconate and dolasetron 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) Administer dolasetron with caution in combination with solifenacin. Solifenacin has been associated with dose-dependent prolongation of the QT interval. Torsade de pointes (TdP) has been reported with postmarketing use, although causality was not determined. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram.
Sorafenib: (Major) Avoid coadministration of sorafenib with dolasetron 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. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram. Sorafenib is also associated with QTc prolongation.
Sotalol: (Major) Use caution during concurrent use of dolasetron and sotalol. Sotalol administration is associated with QT prolongation and torsades de pointes (TdP). Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment. Dolasetron has been associated with a dose-dependant prolongation in the QT, PR, and QRS intervals on an electrocardiogram. Use of dolasetron injection for the prevention of chemotherapy-induced nausea and vomiting is contraindicated because the risk of QT prolongation is higher with the doses required for this indication; when the injection is used at lower doses (i.e., those approved for post-operative nausea and vomiting) or when the oral formulation is used, the risk of QT prolongation is lower and caution is advised.
Spironolactone; Hydrochlorothiazide, HCTZ: (Moderate) Caution is advisable during concurrent use of dolasetron and thiazide diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with dolasetron.
Sufentanil: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering sufentanil with serotonin-receptor antagonists. The development of serotonin syndrome has been reported with 5-HT3 receptor antagonists, mostly when used in combination with other serotonergic medications. Inform patients taking this combination of the possible increased risks and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Sunitinib: (Moderate) Administer dolasetron with caution in combination with sunitinib as concurrent use may increase the risk of QT prolongation. Sunitinib can prolong the QT interval. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram.
Tacrolimus: (Moderate) Consider ECG and electrolyte monitoring periodically during treatment if tacrolimus is administered with dolasetron. Tacrolimus may prolong the QT interval and cause torsade de pointes (TdP). Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram.
Tamoxifen: (Moderate) Concomitant use of tamoxifen and dolasetron 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.
Tapentadol: (Moderate) Because of the potential risk and severity of serotonin syndrome, caution should be observed when administering tapentadol with serotonin-receptor antagonists. The development of serotonin syndrome has been reported with 5-HT3 receptor antagonists, mostly when used in combination with other serotonergic medications. Inform patients taking this combination of the possible increased risks and monitor for the emergence of serotonin syndrome particularly during treatment initiation and dose adjustment. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
Telavancin: (Moderate) Administer dolasetron with caution in combination with telavancin as concurrent use may increase the risk of QT prolongation. Telavancin has been associated with QT prolongation. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram.
Telmisartan; Hydrochlorothiazide, HCTZ: (Moderate) Caution is advisable during concurrent use of dolasetron and thiazide diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with dolasetron.
Tetrabenazine: (Major) Due to a possible risk for QT prolongation and torsade de pointes (TdP), concurrent use of dolasetron and tetrabenazine should be avoided. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram. 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.
Thiazide diuretics: (Moderate) Caution is advisable during concurrent use of dolasetron and thiazide diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with dolasetron.
Thioridazine: (Contraindicated) Because of the potential for torsade de pointes (TdP), use of thioridazine with dolasetron is contraindicated. Thioridazine is associated with a well-established risk of QT prolongation and TdP and is considered contraindicated for use along with agents that may prolong the QT interval and increase the risk of TdP, and/or cause orthostatic hypotension. Dolasetron has also been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram.
Tolterodine: (Moderate) Administer dolasetron with caution in combination with tolterodine as concurrent use may increase the risk of QT prolongation. Tolterodine has been associated with dose-dependent prolongation of the QT interval, especially in poor CYP2D6 metabolizers. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram.
Toremifene: (Major) Avoid coadministration of dolasetron 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. Dolasetron has also been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram.
Torsemide: (Moderate) Caution is advisable during concurrent use of dolasetron and loop diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with dolasetron.
Tramadol: (Major) Because of the potential risk and severity of serotonin syndrome, use caution when administering dolasetron with other drugs that have serotonergic properties such as tramadol. If serotonin syndrome is suspected, discontinue dolasetron and concurrent serotonergic agents and initiate appropriate medical treatment. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death.
Tramadol; Acetaminophen: (Major) Because of the potential risk and severity of serotonin syndrome, use caution when administering dolasetron with other drugs that have serotonergic properties such as tramadol. If serotonin syndrome is suspected, discontinue dolasetron and concurrent serotonergic agents and initiate appropriate medical treatment. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death.
Trandolapril; Verapamil: (Major) Use caution and monitor ECG if a drug known to prolong the PR interval (e.g., verapamil) is combined with dolasetron. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram. Concurrent use may result in additive effects.
Tranylcypromine: (Moderate) Because of the potential risk and severity of serotonin syndrome, use caution when administering dolasetron with other drugs that have serotonergic properties such as monoamine oxidase inhibitors (MAOIs). Serotonin syndrome has been described following the concomitant use of 5-HT3 receptor antagonists and other serotonergic drugs. Monitor for the emergence of serotonin syndrome. If serotonin syndrome is suspected, discontinue dolasetron and concurrent serotonergic agents and initiate appropriate medical treatment.
Trazodone: (Major) Concomitant use of trazodone and dolasetron 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.
Triamterene; Hydrochlorothiazide, HCTZ: (Moderate) Caution is advisable during concurrent use of dolasetron and thiazide diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with dolasetron.
Triclabendazole: (Moderate) Concomitant use of triclabendazole and dolasetron 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) Administer dolasetron with caution in combination with trifluoperazine. Trifluoperazine is associated with a possible risk for QT prolongation. Theoretically, trifluoperazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram.
Triptorelin: (Moderate) Consider whether the benefits of androgen deprivation therapy outweigh the potential risks in patients receiving dolasetron as concurrent use may increase the risk of QT prolongation. Androgen deprivation therapy (i.e., triptorelin) may prolong the QT/QTc interval. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram.
Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) Caution is advisable during concurrent use of dolasetron and thiazide diuretics as electrolyte imbalance caused by diuretics may increase the risk of QT prolongation with dolasetron.
Vandetanib: (Major) Avoid coadministration of vandetanib with dolasetron 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. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram.
Vardenafil: (Moderate) Concomitant use of vardenafil and dolasetron 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) If vemurafenib and dolasetron must be coadministered, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation. Vemurafenib has been associated with QT prolongation. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram. Concurrent use may increase the risk of QT prolongation.
Venlafaxine: (Moderate) Concomitant use of venlafaxine and dolasetron 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.
Verapamil: (Major) Use caution and monitor ECG if a drug known to prolong the PR interval (e.g., verapamil) is combined with dolasetron. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram. Concurrent use may result in additive effects.
Vilazodone: (Major) Because of the potential risk and severity of serotonin syndrome, use caution when administering dolasetron with other drugs that have serotonergic properties such as vilazodone. If serotonin syndrome is suspected, discontinue dolasetron and concurrent serotonergic agents and initiate appropriate medical treatment. Serotonin syndrome is characterized by rapid development of hyperthermia, hypertension, myoclonus, rigidity, autonomic instability, mental status changes (e.g., delirium or coma), and in rare cases, death.
Voclosporin: (Moderate) Concomitant use of voclosporin and dolasetron may increase the risk of QT prolongation. Consider interventions to minimize the risk of progression to torsades 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. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on ECG.
Vonoprazan; Amoxicillin; Clarithromycin: (Contraindicated) Clarithromycin is associated with an established risk for QT prolongation and torsades de pointes (TdP). Clarithromycin should be used cautiously with other agents known to cause QT prolongation. Agents with potential to prolong the QT interval include: dolasetron.
Voriconazole: (Moderate) Administer dolasetron with caution in combination with voriconazole as concurrent use may increase the risk of QT prolongation. Voriconazole has been associated with QT prolongation and rare cases of torsade de pointes. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram.
Vorinostat: (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.
Ziprasidone: (Contraindicated) Concomitant use of ziprasidone and dolasetron is contraindicated by the manufacturer of ziprasidone due to the potential for additive QT prolongation and torsade de pointes (TdP). Clinical trial data indicate that ziprasidone causes QT prolongation; there are postmarketing reports of TdP in patients with multiple confounding factors. Dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram.
Dolasetron and its active metabolite, hydrodolasetron, selectively block type 3 serotonin (5-HT3) receptors. 5-HT3 receptors are found centrally in the chemoreceptor trigger zone and peripherally at vagal nerve terminals in the intestines. Whether the action of dolasetron is mediated centrally, peripherally, or a combination of both remains to be determined. Nausea and vomiting during chemotherapy appears to be associated with the release of serotonin from enterochromaffin cells in the small intestine. Blocking these nerve endings in the intestines prevents signals to the central nervous system.
Dolasetron is administered intravenously or orally. Once in the systemic circulation the parent drug is rapidly eliminated and completely metabolized to hydrodolasetron by the ubiquitous enzyme, carbonyl reductase. Hydrodolasetron is widely distributed in the body and protein binding ranges 69-77% (approximately 50% to alpha-1-acid glycoprotein). Further metabolism of hydrodolasetron occurs primarily via cytochrome P450 2D6 to a hydroxylated metabolite. CYP3A and flavin monooxygenase are responsible for the N-oxidation of hydrodolasetron. Hydrodolasetron elimination is by multiple routes. Two thirds of the administered dose is recovered in the urine and one third in the feces. The elimination half-life of dolasetron and hydrodolasetron is < 10 minutes and 8.1 hours, respectively.
Affected cytochrome P450 isoenzymes: CYP2D6, CYP3A
-Route-Specific Pharmacokinetics
Oral Route
Following oral administration, dolasetron is well absorbed. Peak plasma hydrodolasetron concentrations occur approximately 1 hour after dosing. The apparent absolute bioavailability of oral dolasetron, determined by the major active metabolite hydrodolasetron, is approximately 75%. Food does not affect the oral bioavailability of dolasetron.
-Special Populations
Hepatic Impairment
Dosage adjustments for dolasetron are not needed in patients with hepatic impairment.
Renal Impairment
Dosage adjustments for dolasetron are not needed in patients with renal impairment.
Pediatrics
In pediatric patients, the mean apparent clearance of hydrodolasetron is greater and the half-life shorter compared to healthy adult patients receiving the same dose. In a pharmacokinetic study, the apparent clearance of hydrodolasetron in pediatric and adolescent patients was 1.4 to 2 times higher than in adults. A similar trend was observed in pediatric cancer studies, where the apparent clearance of hydrodolasetron was highest and the half-lives the shortest in the youngest studied age groups. Similarly, in patients undergoing surgery with general anesthesia and given a single 1.2 mg/kg IV dose, the clearance was 40% greater and the terminal half-life 36% shorter for hydrodolasetron compared to healthy adults.
Geriatric
The pharmacokinetics of dolasetron in elderly and younger adult patients are similar. Dosage adjustments are not needed in the elderly.