Kytril

Serotonin/5HT3 Antagonist Antiemetics/antinauseants

Oral Administration

If the patient is prescribed a twice-daily regimen for emetogenic chemotherapy, the first oral dose is administered up to 1 hour before chemotherapy, and the second dose is given 12 hours after the first. The product is given only on the day(s) chemotherapy is given.

Injectable Administration

Visually inspect parenteral products for particulate matter and discoloration prior to administration whenever solution and container permit.

Intravenous Administration

Granisetron hydrochloride injection solution
For intravenous use only.
Administer 30 minutes before the administration of chemotherapy.
 
IV Push
May be given undiluted over 30 seconds via Y-site.
 
Intermittent IV infusion
Prepare IV infusion at the time of administration. Dilute dose in 5% Dextrose or 0.9% Sodium Chloride Injection.
Infuse IV over 5 minutes.
Storage: When diluted as directed, granisetron has been shown to be stable for at least 24 hours and stored at room temperature under normal lighting conditions.

Subcutaneous Administration

Extended-release granisetron subcutaneous injection (Sustol)
Extended-release granisetron injection is for subcutaneous injection only, and is intended for administration by a health care provider.
Do not substitute non-kit components for any of the components from the kit.
 
Preparation of extended-release granisetron injection:
Remove the extended-release granisetron kit from the refrigerator at least 60 minutes prior to administration; all contents should warm to room temperature. If needed, the injection can be placed back in the refrigerator after being kept at room temperature. The injection can remain at room temperature for up to a maximum of 7 days.
Once at room temperature, activate one of the syringe warming pouches. Wrap the syringe of extended-release granisetron in the warming pouch for 5 to 6 minutes to bring it to body temperature.
Do not administer if particulate matter or discoloration is observed, the tip cap is missing or has been tampered with, or if the Luer fitting is missing or dislodged. Note that the syringe is amber-colored glass. The injection is a sterile, clear, colorless to slightly yellow, viscous liquid.
 
Administration of extended-release granisetron injection:
Complete administration instructions with illustrations are available in the extended-release granisetron kit.
A topical anesthetic may be used at the injection site prior to administration. Do not inject extended-release granisetron anywhere the skin is burned, hardened, inflamed, swollen, or otherwise compromised.
Using aseptic technique, administer extended-release granisetron as a single slow subcutaneous injection in the back of the upper arm or the skin of the abdomen (at least 1 inch away from the umbilicus) over up to 20 to 30 seconds; due to viscosity, pressing the plunger harder will not expel extended-release granisetron faster.

Topical Administration Transdermal Patch Formulations

Granisetron transdermal patch (Sancuso)
Each patch releases 3.1 mg of granisetron per 24 hours for up to 7 days.
The patch should be applied directly after the pouch has been opened.
Only one patch should be worn at any time.
Do not cut the patch.
Open the pouch and apply the patch to clean, dry, nearly hairless, intact healthy skin on the upper outer arm. Do not place the patch on skin that is red, irritated, or damaged.
After the patch is applied, wash hands thoroughly.
Do not apply a heat pad or heat lamp over or in the vicinity of the patch and avoid extended exposure to heat.
Cover the application site of the patch with clothing, if there is a risk of exposure to direct natural or artificial sunlight throughout the period of wear and for 10 days following its removal.
Remove the patch by peeling off gently from the skin.
Upon removal, fold the patch in half with the sticky side together, and discard in the household trash in a manner that prevents accidental contact or ingestion by children, pets or others.

Severe

atrial fibrillation / Early / 0-3.0
anaphylactoid reactions / Rapid / 0-3.0
hematoma / Early / 3.0-3.0
injection site reaction / Rapid / 0-3.0
pancreatitis / Delayed / 0-3.0
bleeding / Early / 0-1.0
GI obstruction / Delayed / Incidence not known
ileus / Delayed / Incidence not known
bradycardia / Rapid / Incidence not known
AV block / Early / Incidence not known
seizures / Delayed / Incidence not known
serotonin syndrome / Delayed / Incidence not known
coma / Early / Incidence not known

Moderate

constipation / Delayed / 3.0-22.0
leukopenia / Delayed / 9.0-9.0
elevated hepatic enzymes / Delayed / 2.8-6.0
anemia / Delayed / 4.0-4.0
dyspnea / Early / 0-3.0
hypertension / Early / 1.0-2.0
thrombocytopenia / Delayed / 2.0-2.0
QT prolongation / Rapid / Incidence not known
palpitations / Early / Incidence not known
angina / Early / Incidence not known
chest pain (unspecified) / Early / Incidence not known
hypotension / Rapid / Incidence not known
erythema / Early / Incidence not known
burns / Early / Incidence not known
sinus tachycardia / Rapid / Incidence not known
hyperreflexia / Delayed / Incidence not known
hyperthermia / Delayed / Incidence not known
hallucinations / Early / Incidence not known

Mild

headache / Early / 1.0-21.0
fatigue / Early / 11.0-21.0
nausea / Early / 20.0-20.0
asthenia / Delayed / 2.0-18.0
vomiting / Early / 12.0-12.0
diarrhea / Early / 4.0-9.0
abdominal pain / Early / 4.0-7.0
dyspepsia / Early / 3.0-6.0
anorexia / Delayed / 6.0-6.0
gastroesophageal reflux / Delayed / 0-5.0
dizziness / Early / 3.0-5.0
insomnia / Early / 0-5.0
fever / Early / 3.0-5.0
drowsiness / Early / 1.0-4.0
syncope / Early / 0-3.0
urticaria / Rapid / 0-3.0
alopecia / Delayed / 3.0-3.0
flushing / Rapid / 0-3.0
dysgeusia / Early / 2.0-2.0
anxiety / Delayed / 0-2.0
agitation / Early / 0-2.0
paresthesias / Delayed / 1.0-2.0
rash / Early / 1.0-1.0
infection / Delayed / 0.2-0.4
photosensitivity / Delayed / Incidence not known
skin discoloration / Delayed / Incidence not known
pruritus / Rapid / Incidence not known
skin irritation / Early / Incidence not known
vesicular rash / Delayed / Incidence not known
diaphoresis / Early / Incidence not known
tremor / Early / Incidence not known

Kytril, Sancuso, Sustol

Rx

Oral/intravenous/subcutaneous/transdermal 5-HT3 antagonist
Used to offset nausea/vomiting from moderately or highly emetogenic chemotherapy; also used for prevention of radiation-induced nausea/vomiting, and the immediate-release IV formulation is also approved for postoperative nausea/vomiting
Risk of dose-dependent QT prolongation and torsades de pointes

For chemotherapy-induced nausea/vomiting (CINV) and chemotherapy-induced nausea/vomiting prophylaxis. For chemotherapy-induced nausea/vomiting (CINV) prophylaxis in patients receiving moderately and/or highly emetogenic chemotherapy for up to 5 consecutive days. Transdermal dosage Adults

Apply 1 patch (3.1 mg/24 hours) to upper outer arm a minimum of 24 hours, up to a maximum of 48 hours, before chemotherapy. The patch should be worn at minimum, 24 hours after chemotherapy is finished. The patch can be worn for up to 7 days.

For acute and delayed chemotherapy induced nausea/vomiting (CINV) prophylaxis associated with moderately emetogenic chemotherapy (MEC) or anthracycline and cyclophosphamide chemotherapy regimens, in combination with other antiemetics. Subcutaneous dosage Adults

10 mg subcutaneously on day 1, in combination with dexamethasone (MEC, 8 mg IV on day 1; AC regimens, 20 mg IV on day 1, followed by 8mg by mouth twice daily on days 2, 3, and 4), at least 30 minutes before initiation of chemotherapy; do not administer more frequently than every 7 days. If an NK1 receptor antagonist is also being administered, refer to the NK1 receptor antagonist monograph for dexamethasone dosing. In a randomized, multicenter, double-blind, parallel group study, intravenous extended-release granisetron was found to be non-inferior to palonosetron in both the acute and delayed settings. A complete response (CR) (no emesis and no rescue medications) was achieved in 83% of granisetron-treated patients (n = 200) in the acute phase after MEC compared with 89% of those who received palonosetron (n = 206); in the delayed phase, a CR was achieved in 69% vs. 70% of patients, respectively. After AC combination chemotherapy, CR in the acute phase was achieved in 70% vs. 64% of patients, respectively, and in 50% vs. 47% in the delayed phase.

For chemotherapy-induced nausea/vomiting (CINV) prophylaxis, including for high-dose cisplatin. Intravenous dosage Adults

10 mcg/kg IV within 30 minutes before beginning emetogenic chemotherapy. Doses as high as 40 mcg/kg IV have been used in clinical trials, but were not significantly superior to the recommended dose.

Children and Adolescents 2 years and older

10 mcg/kg, 20 mcg/kg, or 40 mcg/kg IV depending on protocol and practice setting; administer within 30 to 60 minutes before beginning emetogenic chemotherapy. 10 mcg/kg IV is the FDA-approved dose and has been established in clinical practice ; however, 20 mcg/kg and 40 mcg/kg doses have also been used in clinical practice. The Pediatric Oncology Group of Ontario (POGO) recommends granisetron 40 mcg/kg IV as a single daily dose prior to chemotherapy.

Oral dosage Adults

1 mg PO twice daily on days of chemotherapy administration. Give first dose up to 60 minutes before chemotherapy; give the second dose 12 hours later. Alternatively, give 2 mg as a single dose within 1 hour prior to chemotherapy.

Children and Adolescents 2 years and older†

40 mcg/kg/dose PO every 12 hours is recommended by the Pediatric Oncology Group of Ontario (POGO) for children receiving moderate or low emetogenic risk chemotherapy. Although no maximum dosage is defined, the usual adult dose given twice daily is 1 mg.

For chemotherapy-induced nausea/vomiting (CINV) prophylaxis in patients receiving highly emetogenic chemotherapy (HEC), in combination with fosaprepitant and dexamethasone†. Subcutaneous dosage Adults

10 mg subcutaneously on day 1, in combination with fosaprepitant 150 mg IV and dexamethasone, at least 30 minutes before initiation of chemotherapy. The FDA-approved labelling for prophylaxis of AC chemotherapy recommends dexamethasone 20 mg IV on day 1, followed by 8mg PO twice daily on days 2, 3, and 4, while another clinical trial has used dexamethasone 12 mg IV on day 1, followed by 8 mg by mouth for one dose on day 2 and twice daily on days 3 and 4. Extended-release granisetron improved the rate of complete response in the delayed phase after administration of highly-emetogenic chemotherapy (HEC) (no emesis, no rescue medications) compared with ondansetron (64.7% vs. 56.6%; p = 0.014), both given in combination with fosaprepitant and dexamethasone, in a multicenter, randomized, double-blind, placebo-controlled phase III clinical trial; overall nausea/vomiting was also improved in the granisetron arm (58.4% vs. 52.9%; adjusted p = 0.275).

For radiation-induced nausea/vomiting prophylaxis. Oral dosage Adults

2 mg PO single dose given within 1 hour of radiation.

For the treatment of post-operative nausea/vomiting (PONV)†.
NOTE: The FDA-approved product label recommends against granisetron for postoperative nausea/vomiting (PONV) due to lack of efficacy and risk of QT prolongation.
Intravenous dosage Adults

According to treatment guidelines, therapy with small-dose 5-HT3 receptor antagonists (e.g., 0.1 mg granisetron) should be initiated on the first signs of PONV. Small-doses, about 1/4 of the dose used for prophylaxis, are generally recommended for patients who did not receive prophylactic therapy. Doses in the range of 0.1 to 3 mg IV have been studied. Overall, data from a systematic review of antiemetic therapy revealed little evidence of dose-responsiveness with 5-HT3 receptor antagonists; however, some clinically relevant benefits were seen from higher granisetron doses, with increased response in the early and late treatment of active vomiting. Less efficacy was seen with 5-HT3 receptor antagonists in preventing further nausea in a nauseated patient.

For post-operative nausea/vomiting (PONV) prophylaxis†. Intravenous dosage Adults

0.35 to 3 mg (5 to 20 mcg/kg) IV at the end of surgery is as effective at preventing PONV as other first generation 5HT3 receptor antagonists, per treatment guidelines. Of note, current manufacturer labeling does not list an indication for PONV prophylaxis ; however, granisetron continues to be an effective alternative in PONV prophylaxis. Earlier package inserts recommended 1 mg IV push before induction of anesthesia or immediately before reversal of anesthesia to prevent PONV.

Oral dosage Children and Adolescents

20 mcg/kg or 40 mcg/kg (Max: 1 mg) PO 20 minutes before induction of anesthesia was effective in children undergoing strabismus surgery. In a randomized, double-blind, placebo-controlled trial, 73 pediatric patients received granisetron 20 mcg/kg, 40 mcg/kg, or placebo 20 minutes prior to strabismus repair surgery. Granisetron 20 and 40 mcg/kg were more effective than placebo in decreasing the incidence of PONV in the first 24 hours (29% in granisetron groups vs. 84% in placebo group, p < 0.05) and the number of children experiencing severe vomiting was reduced in the granisetron 20 mcg/kg and 40 mcg/kg groups compared to placebo (4%, 8%, and 48%, respectively, p < 0.05).

†Indicates off-label use

Hepatic Impairment

No dosage adjustment is recommended for hepatic impairment.

Renal Impairment

Granisetron Injection, Tablet or oral solution, and Transdermal Patch: No dosage adjustment is recommended.
 
Granisetron Extended-Release Subcutaneous Injection:
Moderate renal impairment (CrCL 30 to 59 mL/minute): Do not administer more frequently than once every 14 days.
Severe renal impairment (CrCL less than 30 mL/minute): Avoid use.

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) Avoid concomitant use of adagrasib and granisetron due to the potential for increased granisetron exposure and additive risk for QT/QTc prolongation and torsade de pointes (TdP). If use is necessary, monitor for granisetron-related adverse effects and consider taking additional steps to minimize the risk for QT prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring. Granisetron is a CYP3A substrate, adagrasib is a strong CYP3A inhibitor, and both medications have been associated with QT interval prolongation.
Alfentanil: (Moderate) If concomitant use of alfentanil and granisetron 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) Use granisetron with caution in combination with alfuzosin due to the risk of QT prolongation. Alfuzosin may prolong the QT interval in a dose-dependent manner. Granisetron has been associated with QT prolongation.
Aliskiren; Hydrochlorothiazide, HCTZ: (Moderate) According to the manufacturer, caution is warranted when administering granisetron to patients with preexisting electrolyte abnormalities. Patients taking certain diuretics may develop an electrolyte abnormality that may lead to cardiac dysrhythmias and/or QT prolongation. Hypokalemia or hypomagnesemia may occur with administration of potassium-depleting drugs such as loop diuretics and thiazide diuretics, increasing the potential for cardiac arrhythmias.
Amiloride; Hydrochlorothiazide, HCTZ: (Moderate) According to the manufacturer, caution is warranted when administering granisetron to patients with preexisting electrolyte abnormalities. Patients taking certain diuretics may develop an electrolyte abnormality that may lead to cardiac dysrhythmias and/or QT prolongation. Hypokalemia or hypomagnesemia may occur with administration of potassium-depleting drugs such as loop diuretics and thiazide diuretics, increasing the potential for cardiac arrhythmias.
Amiodarone: (Major) Granisetron has been associated with QT prolongation. According to the manufacturer, use of granisetron in patients concurrently treated with drugs known to prolong the QT interval and/or are arrhythmogenic, may result in clinical consequences. If possible, avoid coadministration of amiodarone and drugs known to prolong the QT interval. Amiodarone, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and torsades de pointes (TdP). Although the frequency of TdP is less with amiodarone than with other Class III agents, amiodarone is still associated with a risk of TdP. Due to the extremely long half-life of amiodarone, a drug interaction is possible for days to weeks after discontinuation of amiodarone.
Amisulpride: (Major) Monitor ECGs for QT prolongation when amisulpride is administered with granisetron. Amisulpride causes dose- and concentration- dependent QT prolongation. Granisetron has been associated with QT prolongation.
Amlodipine; Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) According to the manufacturer, caution is warranted when administering granisetron to patients with preexisting electrolyte abnormalities. Patients taking certain diuretics may develop an electrolyte abnormality that may lead to cardiac dysrhythmias and/or QT prolongation. Hypokalemia or hypomagnesemia may occur with administration of potassium-depleting drugs such as loop diuretics and thiazide diuretics, increasing the potential for cardiac arrhythmias.
Amoxicillin; Clarithromycin; Omeprazole: (Major) Due to an increased risk for QT prolongation and torsade de pointes (TdP), caution is advised when administering clarithromycin with granisetron. Both granisetron and clarithromycin are associated with prolongation of the QT interval, and clarithromycin has also been associated with an established risk for TdP.
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 granisetron.
Apalutamide: (Moderate) Monitor for decreased efficacy of granisetron if coadministration with apalutamide is necessary. Granisetron is a CYP3A4 substrate and apalutamide is a strong CYP3A4 inducer. In a human pharmacokinetic study, coadministration with another strong CYP3A4 inducer increased the total plasma clearance of granisetron by 25%. The clinical significance of this change is not known.
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 granisetron. Granisetron 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 and theoretically could increase plasma concentrations of granisetron. 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 granisetron. After administration, fosaprepitant is rapidly converted to aprepitant and shares many of the same drug interactions. However, as a single 150 mg intravenous dose, fosaprepitant only weakly inhibits CYP3A4 for a duration of 2 days; there is no evidence of CYP3A4 induction.
Aripiprazole: (Moderate) Concomitant use of aripiprazole and granisetron 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 granisetron. If concomitant drug use is unavoidable, frequently monitor electrocardiograms. Torsade de pointes (TdP), QT interval prolongation, and complete atrioventricular block have been reported with arsenic trioxide use. Granisetron has also been associated with QT prolongation. Concurrent use may result in additive risk of QT prolongation.
Artemether; Lumefantrine: (Major) Concurrent use of granisetron and artemether; lumefantrine should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Consider ECG monitoring if granisetron must be used with or after artemether; lumefantrine treatment. Both granisetron and artemether; lumefantrine are associated with prolongation of the QT interval.
Asenapine: (Major) 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, such as granisetron. Granisetron has been associated with QT prolongation. According to the manufacturer, the use of granisetron in patients concurrently treated with drugs known to prolong the QT interval (e.g., asenapine) and/or are arrhythmogenic, may result in clinical consequences.
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: (Minor) The plasma concentrations of granisetron may be elevated when administered concurrently with atazanavir. Clinical monitoring for adverse effects, such as GI or CNS effects, is recommended during coadministration. Atazanavir is a CYP3A4 inhibitor, while granisetron is a CYP3A4 substrate.
Atazanavir; Cobicistat: (Minor) Plasma concentrations of granisetron may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as GI or CNS effects, is recommended during coadministration. Cobicistat is a CYP3A4 inhibitor, while granisetron is a CYP3A4 substrate. (Minor) The plasma concentrations of granisetron may be elevated when administered concurrently with atazanavir. Clinical monitoring for adverse effects, such as GI or CNS effects, is recommended during coadministration. Atazanavir is a CYP3A4 inhibitor, while granisetron is a CYP3A4 substrate.
Atenolol; Chlorthalidone: (Moderate) According to the manufacturer, caution is warranted when administering granisetron to patients with preexisting electrolyte abnormalities. Patients taking certain diuretics may develop an electrolyte abnormality that may lead to cardiac dysrhythmias and/or QT prolongation. Hypokalemia or hypomagnesemia may occur with administration of potassium-depleting drugs such as loop diuretics and thiazide diuretics, increasing the potential for cardiac arrhythmias.
Atomoxetine: (Moderate) Concomitant use of atomoxetine and granisetron 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) According to the manufacturer, caution is warranted when administering granisetron to patients with preexisting electrolyte abnormalities. Patients taking certain diuretics may develop an electrolyte abnormality that may lead to cardiac dysrhythmias and/or QT prolongation. Hypokalemia or hypomagnesemia may occur with administration of potassium-depleting drugs such as loop diuretics and thiazide diuretics, increasing the potential for cardiac arrhythmias.
Azithromycin: (Major) Avoid coadministration of azithromycin with granisetron 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. Granisetron has been associated with QT prolongation.
Bedaquiline: (Major) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering bedaquiline with granisetron. Both drugs have been reported to prolong the QT interval. Prior to initiating bedaquiline, obtain serum electrolyte concentrations and a baseline ECG. An ECG should also be performed at least 2, 12, and 24 weeks after starting bedaquiline therapy.
Benazepril; Hydrochlorothiazide, HCTZ: (Moderate) According to the manufacturer, caution is warranted when administering granisetron to patients with preexisting electrolyte abnormalities. Patients taking certain diuretics may develop an electrolyte abnormality that may lead to cardiac dysrhythmias and/or QT prolongation. Hypokalemia or hypomagnesemia may occur with administration of potassium-depleting drugs such as loop diuretics and thiazide diuretics, increasing the potential for cardiac arrhythmias.
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 granisetron with other drugs that have serotonergic properties such as methylene blue. If serotonin syndrome is suspected, discontinue granisetron 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 granisetron 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 granisetron 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) According to the manufacturer, caution is warranted when administering granisetron to patients with preexisting electrolyte abnormalities. Patients taking certain diuretics may develop an electrolyte abnormality that may lead to cardiac dysrhythmias and/or QT prolongation. Hypokalemia or hypomagnesemia may occur with administration of potassium-depleting drugs such as loop diuretics and thiazide diuretics, increasing the potential for cardiac arrhythmias.
Bumetanide: (Moderate) According to the manufacturer, caution is warranted when administering granisetron to patients with preexisting electrolyte abnormalities. Patients taking certain diuretics may develop an electrolyte abnormality that may lead to cardiac dysrhythmias and/or QT prolongation. Hypokalemia or hypomagnesemia may occur with administration of potassium-depleting drugs such as loop diuretics and thiazide diuretics, increasing the potential for cardiac arrhythmias.
Buprenorphine: (Major) Buprenorphine has been associated with QT prolongation and has a possible risk of torsade de pointes (TdP). Granisetron also has a possible risk for QT prolongation and 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. In addition, concurrent use of opioids with other drugs that modulate serotonergic function, such as granisetron, has resulted in serotonin syndrome in some cases. 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 combination treatment with buprenorphine and ganisetron is required, patients should be carefully observed, particularly during treatment initiation and during dose adjustments of the serotonergic drug; discontinue buprenorphine if serotonin syndrome is suspected.
Buprenorphine; Naloxone: (Major) Buprenorphine has been associated with QT prolongation and has a possible risk of torsade de pointes (TdP). Granisetron also has a possible risk for QT prolongation and 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. In addition, concurrent use of opioids with other drugs that modulate serotonergic function, such as granisetron, has resulted in serotonin syndrome in some cases. 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 combination treatment with buprenorphine and ganisetron is required, patients should be carefully observed, particularly during treatment initiation and during dose adjustments of the serotonergic drug; discontinue buprenorphine if serotonin syndrome is suspected.
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) Use granisetron with caution in combination with rilpivirine due to the risk of QT prolongation. Granisetron has been associated with QT prolongation. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation.
Candesartan; Hydrochlorothiazide, HCTZ: (Moderate) According to the manufacturer, caution is warranted when administering granisetron to patients with preexisting electrolyte abnormalities. Patients taking certain diuretics may develop an electrolyte abnormality that may lead to cardiac dysrhythmias and/or QT prolongation. Hypokalemia or hypomagnesemia may occur with administration of potassium-depleting drugs such as loop diuretics and thiazide diuretics, increasing the potential for cardiac arrhythmias.
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) According to the manufacturer, caution is warranted when administering granisetron to patients with preexisting electrolyte abnormalities. Patients taking certain diuretics may develop an electrolyte abnormality that may lead to cardiac dysrhythmias and/or QT prolongation. Hypokalemia or hypomagnesemia may occur with administration of potassium-depleting drugs such as loop diuretics and thiazide diuretics, increasing the potential for cardiac arrhythmias.
Celecoxib; Tramadol: (Major) Because of the potential risk and severity of serotonin syndrome, use caution when administering granisetron with other drugs that have serotonergic properties such as tramadol. If serotonin syndrome is suspected, discontinue granisetron 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.
Ceritinib: (Major) Avoid coadministration of ceritinib with granisetron if possible due to the risk of QT prolongation. If concomitant use is unavoidable, periodically monitor ECGs and electrolytes; an interruption of ceritinib therapy, dose reduction, or discontinuation of therapy may be necessary if QT prolongation occurs. Ceritinib causes concentration-dependent prolongation of the QT interval. Granisetron has also been associated with QT prolongation.
Chloroquine: (Major) Avoid coadministration of chloroquine with granisetron 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. Granisetron has been associated with QT prolongation.
Chlorothiazide: (Moderate) According to the manufacturer, caution is warranted when administering granisetron to patients with preexisting electrolyte abnormalities. Patients taking certain diuretics may develop an electrolyte abnormality that may lead to cardiac dysrhythmias and/or QT prolongation. Hypokalemia or hypomagnesemia may occur with administration of potassium-depleting drugs such as loop diuretics and thiazide diuretics, increasing the potential for cardiac arrhythmias.
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; Dihydrocodeine; Phenylephrine: (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.
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), granisetron and chlorpromazine should be used together cautiously. Granisetron has been associated with QT prolongation. According to the manufacturer, use of granisetron with drugs known to prolong the QT interval or are arrhythmogenic, may result in clinical consequences. Phenothiazines have been associated with a risk of QT prolongation or TdP. This risk is generally higher at elevated concentrations of phenothiazines. Chlorpromazine is specifically associated with an established risk of QT prolongation and TdP; case reports have included patients receiving therapeutic doses of chlorpromazine. Agents that prolong the QT interval could lead to torsade de pointes when combined with a phenothiazine, and therefore are generally not recommended for combined use.
Chlorthalidone: (Moderate) According to the manufacturer, caution is warranted when administering granisetron to patients with preexisting electrolyte abnormalities. Patients taking certain diuretics may develop an electrolyte abnormality that may lead to cardiac dysrhythmias and/or QT prolongation. Hypokalemia or hypomagnesemia may occur with administration of potassium-depleting drugs such as loop diuretics and thiazide diuretics, increasing the potential for cardiac arrhythmias.
Chlorthalidone; Clonidine: (Moderate) According to the manufacturer, caution is warranted when administering granisetron to patients with preexisting electrolyte abnormalities. Patients taking certain diuretics may develop an electrolyte abnormality that may lead to cardiac dysrhythmias and/or QT prolongation. Hypokalemia or hypomagnesemia may occur with administration of potassium-depleting drugs such as loop diuretics and thiazide diuretics, increasing the potential for cardiac arrhythmias.
Ciprofloxacin: (Moderate) Concomitant use of ciprofloxacin and granisetron 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) Granisetron has been associated with QT prolongation. According to the manufacturer, use of granisetron with drugs known to prolong the QT interval or are arrhythmogenic, may result in clinical consequences. Because of the potential for torsade de pointes (TdP), use of cisapride with granisetron is contraindicated.
Citalopram: (Major) Because of the potential risk and severity of serotonin syndrome or QT prolongation, use caution and monitor closely when administering granisetron with other drugs that have serotonergic properties or may prolong the QT interval, such as citalopram. If serotonin syndrome is suspected, discontinue granisetron 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. In addition, granisetron has been associated with QT prolongation. According to the product labeling, use of granisetron in patients concurrently treated with drugs known to prolong the QT interval and/or are arrhythmogenic, may result in clinical consequences.
Clarithromycin: (Major) Due to an increased risk for QT prolongation and torsade de pointes (TdP), caution is advised when administering clarithromycin with granisetron. Both granisetron and clarithromycin are associated with prolongation of the QT interval, and clarithromycin has also been associated with an established risk for TdP.
Class IA Antiarrhythmics: (Major) Granisetron should be used cautiously and with close monitoring with Class IA antiarrhythmics (disopyramide, procainamide, and quinidine). Class IA antiarrhythmics are associated with QT prolongation and torsades de pointes (TdP). Granisetron has been associated with QT prolongation. According to the manufacturer, use of granisetron in patients concurrently treated with drugs known to prolong the QT interval and/or are arrhythmogenic, may result in clinical consequences.
Clofazimine: (Moderate) Concomitant use of clofazimine and granisetron 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) Use clozapine with caution in combination with granisteron. Treatment with clozapine has been associated with QT prolongation, torsade de pointes (TdP), cardiac arrest, and sudden death. Granisetron has been associated with QT prolongation.
Cobicistat: (Minor) Plasma concentrations of granisetron may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as GI or CNS effects, is recommended during coadministration. Cobicistat is a CYP3A4 inhibitor, while granisetron is a CYP3A4 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 granisetron 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 granisetron 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 granisetron 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. Granisetron has also been associated with QT prolongation.
Cyclobenzaprine: (Major) Because of the potential risk and severity of serotonin syndrome, use caution when administering granisetron with other drugs that have serotonergic properties such as cyclobenzaprine. 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. If serotonin syndrome is suspected, granisetron and concurrent serotonergic agents should be discontinued and appropriate medical treatment should be initiated.
Darunavir: (Minor) The plasma concentrations of granisetron may be elevated when administered concurrently with darunavir. Clinical monitoring for adverse effects, such as GI or CNS effects, is recommended during coadministration. Darunavir is a CYP3A4 inhibitor, while granisetron is a CYP3A4 substrate.
Darunavir; Cobicistat: (Minor) Plasma concentrations of granisetron may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as GI or CNS effects, is recommended during coadministration. Cobicistat is a CYP3A4 inhibitor, while granisetron is a CYP3A4 substrate. (Minor) The plasma concentrations of granisetron may be elevated when administered concurrently with darunavir. Clinical monitoring for adverse effects, such as GI or CNS effects, is recommended during coadministration. Darunavir is a CYP3A4 inhibitor, while granisetron is a CYP3A4 substrate.
Darunavir; Cobicistat; Emtricitabine; Tenofovir alafenamide: (Minor) Plasma concentrations of granisetron may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as GI or CNS effects, is recommended during coadministration. Cobicistat is a CYP3A4 inhibitor, while granisetron is a CYP3A4 substrate. (Minor) The plasma concentrations of granisetron may be elevated when administered concurrently with darunavir. Clinical monitoring for adverse effects, such as GI or CNS effects, is recommended during coadministration. Darunavir is a CYP3A4 inhibitor, while granisetron is a CYP3A4 substrate.
Dasatinib: (Moderate) Use granisetron with caution in combination with dasatinib due to the risk of QT prolongation. Granisetron has been associated with QT prolongation. 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 (i.e., degarelix) outweigh the potential risks in patients receiving granisetron as concurrent use may increase the risk of QT prolongation. Androgen deprivation therapy may prolong the QT/QTc interval. Granisetron has been associated with QT prolongation.
Desvenlafaxine: (Major) Because of the potential risk and severity of serotonin syndrome, use caution when administering granisetron with other drugs that have serotonergic properties such as desvenlafaxine. If serotonin syndrome is suspected, discontinue granisetron 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.
Deutetrabenazine: (Moderate) Use granisetron with caution in combination with deutetrabenazine. Granisetron has been associated with QT prolongation. 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 granisetron may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Dextromethorphan; Quinidine: (Major) Granisetron should be used cautiously and with close monitoring with Class IA antiarrhythmics (disopyramide, procainamide, and quinidine). Class IA antiarrhythmics are associated with QT prolongation and torsades de pointes (TdP). Granisetron has been associated with QT prolongation. According to the manufacturer, use of granisetron in patients concurrently treated with drugs known to prolong the QT interval and/or are arrhythmogenic, may result in clinical consequences.
Disopyramide: (Major) Granisetron should be used cautiously and with close monitoring with Class IA antiarrhythmics (disopyramide, procainamide, and quinidine). Class IA antiarrhythmics are associated with QT prolongation and torsades de pointes (TdP). Granisetron has been associated with QT prolongation. According to the manufacturer, use of granisetron in patients concurrently treated with drugs known to prolong the QT interval and/or are arrhythmogenic, may result in clinical consequences.
Dofetilide: (Major) Coadministration of dofetilide and granisetron 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). Granisetron has been associated with QT prolongation.
Dolasetron: (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.
Dolutegravir; Rilpivirine: (Moderate) Use granisetron with caution in combination with rilpivirine due to the risk of QT prolongation. Granisetron has been associated with QT prolongation. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation.
Donepezil: (Moderate) Use donepezil with caution in combination with granisetron as concurrent use may increase the risk of QT prolongation. Case reports indicate that QT prolongation and torsade de pointes (TdP) can occur during donepezil therapy. Granisetron has been associated with QT prolongation.
Donepezil; Memantine: (Moderate) Use donepezil with caution in combination with granisetron as concurrent use may increase the risk of QT prolongation. Case reports indicate that QT prolongation and torsade de pointes (TdP) can occur during donepezil therapy. Granisetron has been associated with QT prolongation.
Dronedarone: (Contraindicated) Concurrent use of granisetron and dronedarone is contraindicated. Granisetron has been associated with QT prolongation. According to the manufacturer, use of granisetron in patients concurrently treated with drugs known to prolong the QT interval and/or are arrhythmogenic, may result in clinical consequences. Dronedarone administration is associated with a dose-related increase in the QTc interval. The increase in QTc is approximately 10 milliseconds at doses of 400 mg twice daily (the FDA-approved dose) and up to 25 milliseconds at doses of 1600 mg twice daily. Although there are no studies examining the effects of dronedarone in patients receiving other QT prolonging drugs, coadministration of such drugs may result in additive QT prolongation.
Droperidol: (Major) Droperidol should be administered with extreme caution to patients receiving other agents that may prolong the QT interval. Droperidol administration is associated with an established risk for QT prolongation and torsades de pointes (TdP). Any drug known to have potential to prolong the QT interval should not be coadministered with droperidol. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with droperidol include granisetron.
Duloxetine: (Major) Because of the potential risk and severity of serotonin syndrome, use caution when administering granisetron with other drugs that have serotonergic properties such as duloxetine. If serotonin syndrome is suspected, discontinue granisetron 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 granisetron as concurrent use may increase the risk of QT prolongation. QT prolongation has been observed with use of efavirenz. Granisetron has also been associated with QT prolongation.
Efavirenz; Emtricitabine; Tenofovir Disoproxil Fumarate: (Moderate) Consider alternatives to efavirenz when coadministering with granisetron as concurrent use may increase the risk of QT prolongation. QT prolongation has been observed with use of efavirenz. Granisetron has also been associated with QT prolongation.
Efavirenz; Lamivudine; Tenofovir Disoproxil Fumarate: (Moderate) Consider alternatives to efavirenz when coadministering with granisetron as concurrent use may increase the risk of QT prolongation. QT prolongation has been observed with use of efavirenz. Granisetron has also been associated with QT prolongation.
Elbasvir; Grazoprevir: (Minor) Administering granisetron with grazoprevir may result in elevated granisetron plasma concentrations. Granisetron 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: (Minor) Use granisetron with caution in combination with elglustat due to the risk of QT prolongation. Eliglustat is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. Granisetron has been associated with QT prolongation.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Alafenamide: (Minor) Plasma concentrations of granisetron may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as GI or CNS effects, is recommended during coadministration. Cobicistat is a CYP3A4 inhibitor, while granisetron is a CYP3A4 substrate.
Elvitegravir; Cobicistat; Emtricitabine; Tenofovir Disoproxil Fumarate: (Minor) Plasma concentrations of granisetron may be elevated when administered concurrently with cobicistat. Clinical monitoring for adverse effects, such as GI or CNS effects, is recommended during coadministration. Cobicistat is a CYP3A4 inhibitor, while granisetron is a CYP3A4 substrate.
Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Moderate) Use granisetron with caution in combination with rilpivirine due to the risk of QT prolongation. Granisetron has been associated with QT prolongation. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation.
Emtricitabine; Rilpivirine; Tenofovir Disoproxil Fumarate: (Moderate) Use granisetron with caution in combination with rilpivirine due to the risk of QT prolongation. Granisetron has been associated with QT prolongation. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation.
Enalapril; Hydrochlorothiazide, HCTZ: (Moderate) According to the manufacturer, caution is warranted when administering granisetron to patients with preexisting electrolyte abnormalities. Patients taking certain diuretics may develop an electrolyte abnormality that may lead to cardiac dysrhythmias and/or QT prolongation. Hypokalemia or hypomagnesemia may occur with administration of potassium-depleting drugs such as loop diuretics and thiazide diuretics, increasing the potential for cardiac arrhythmias.
Encorafenib: (Major) Avoid coadministration of encorafenib and granisetron 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. Granisetron has also been associated with QT prolongation.
Entrectinib: (Major) Avoid coadministration of entrectinib with granisetron due to the risk of QT prolongation. Both entrectinib and granisetron have been associated with QT prolongation.
Enzalutamide: (Moderate) Monitor for decreased efficacy of granisetron if coadministration with enzalutamide is necessary. Granisetron is a CYP3A4 substrate and enzalutamide is a strong CYP3A4 inducer. In a human pharmacokinetic study, coadministration with another strong CYP3A4 inducer increased the total plasma clearance of granisetron by 25%. The clinical significance of this change is not known.
Eprosartan; Hydrochlorothiazide, HCTZ: (Moderate) According to the manufacturer, caution is warranted when administering granisetron to patients with preexisting electrolyte abnormalities. Patients taking certain diuretics may develop an electrolyte abnormality that may lead to cardiac dysrhythmias and/or QT prolongation. Hypokalemia or hypomagnesemia may occur with administration of potassium-depleting drugs such as loop diuretics and thiazide diuretics, increasing the potential for cardiac arrhythmias.
Eribulin: (Major) Eribulin has been associated with QT prolongation. If eribulin and another drug that prolongs the QT interval must be coadministered, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation. Drugs with a possible risk for QT prolongation and torsades de pointes (TdP) that should be used cautiously with eribulin include granisetron.
Erythromycin: (Major) Due to a possible risk for QT prolongation and torsade de pointes (TdP), granisetron and erythromycin should be used together cautiously. Granisetron has been associated with QT prolongation. According to the manufacturer, use of granisetron with drugs known to prolong the QT interval or are arrhythmogenic, may result in clinical consequences. Erythromycin administration is associated with QT prolongation and TdP.
Escitalopram: (Moderate) Concomitant use of escitalopram and granisetron 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) According to the manufacturer, caution is warranted when administering granisetron to patients with preexisting electrolyte abnormalities. Patients taking certain diuretics may develop an electrolyte abnormality that may lead to cardiac dysrhythmias and/or QT prolongation. Hypokalemia or hypomagnesemia may occur with administration of potassium-depleting drugs such as loop diuretics and thiazide diuretics, increasing the potential for cardiac arrhythmias.
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 granisetron with other drugs that have serotonergic properties such as fentanyl. If serotonin syndrome is suspected, discontinue granisetron 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.
Fingolimod: (Moderate) Use granisetron with caution in combination with fingolimod due to the risk of QT prolongation. Fingolimod initiation results in decreased heart rate and may prolong the QT interval. Fingolimod has not been studied in patients treated with drugs that prolong the QT interval, but drugs that prolong the QT interval have been associated with cases of TdP in patients with bradycardia. Granisetron has been associated with QT prolongation.
Flecainide: (Major) Flecainide should be used cautiously and with close monitoring with granisetron. Granisetron has been associated with QT prolongation. According to the manufacturer, use of granisetron in patients concurrently treated with drugs known to prolong the QT interval and/or are arrhythmogenic, may result in clinical consequences. 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 granisetron 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) Use fluoxetine with caution in combination with granisteron as there is an increased risk for QT prolongation, torsade de pointes (TdP), and serotonin syndrome. If serotonin syndrome is suspected, discontinue granisetron and concurrent serotonergic agents and initiate appropriate medical treatment. QT prolongation and TdP have been reported in patients treated with fluoxetine. Granisetron has also been associated with QT prolongation.
Fluphenazine: (Minor) Use granisetron with caution in combination with fluphenazine due to the risk of QT prolongation. Theoretically, fluphenazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation, such as granisetron.
Fluvoxamine: (Moderate) Use granisetron with caution in combination with fluvoxamine due to increased the risk of serotonin syndrome, QT prolongation, and torsade de pointes. If serotonin syndrome occurs, all serotonergic agents should be discontinued and appropriate medical treatment should be implemented. Cases of QT prolongation and TdP have been reported during postmarketing use of fluvoxamine. Granisetron has been associated with QT prolongation.
Foscarnet: (Major) When possible, avoid concurrent use of foscarnet with other drugs known to prolong the QT interval, such as granisetron. Foscarnet has been associated with postmarketing reports of both QT prolongation and torsade de pointes (TdP). Granisetron has also been associated with QT prolongation. If these drugs are administered together, obtain an electrocardiogram and electrolyte concentrations before and periodically during treatment.
Fosinopril; Hydrochlorothiazide, HCTZ: (Moderate) According to the manufacturer, caution is warranted when administering granisetron to patients with preexisting electrolyte abnormalities. Patients taking certain diuretics may develop an electrolyte abnormality that may lead to cardiac dysrhythmias and/or QT prolongation. Hypokalemia or hypomagnesemia may occur with administration of potassium-depleting drugs such as loop diuretics and thiazide diuretics, increasing the potential for cardiac arrhythmias.
Fostemsavir: (Moderate) Use granisetron with caution in combination with fostemsavir due to the risk of QT prolongation. Granisetron has been associated with QT prolongation. 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) According to the manufacturer, caution is warranted when administering granisetron to patients with preexisting electrolyte abnormalities. Patients taking certain diuretics may develop an electrolyte abnormality that may lead to cardiac dysrhythmias and/or QT prolongation. Hypokalemia or hypomagnesemia may occur with administration of potassium-depleting drugs such as loop diuretics and thiazide diuretics, increasing the potential for cardiac arrhythmias.
Gemifloxacin: (Moderate) Use granisetron with caution in combination with gemifloxacin due to an increased risk for QT prolongation and torsade de pointes (TdP). Granisetron has been associated with QT prolongation. Gemifloxacin may prolong the QT interval in some patients, with the maximal change in the QTc interval occurring approximately 5 to 10 hours following oral administration. The likelihood of QTc prolongation may increase with increasing dose of gemifloxacin; therefore, the recommended dose should not be exceeded especially in patients with renal or hepatic impairment where the Cmax and AUC are slightly higher.
Gemtuzumab Ozogamicin: (Moderate) Use gemtuzumab ozogamicin and granisetron together with caution due to the potential for additive QT interval prolongation and risk of torsade de pointes (TdP). If these agents are used together, obtain an ECG and serum electrolytes prior to the start of gemtuzumab and as needed during treatment. Granisetron has been associated with QT prolongation. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin.
Gilteritinib: (Moderate) Use caution and monitor for evidence of QT prolongation if concurrent use of gilteritinib and granisetron is necessary. Both drugs have been associated with QT prolongation.
Glasdegib: (Major) Avoid coadministration of glasdegib with granisetron 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. Granisetron has also been associated with QT prolongation.
Goserelin: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., goserelin) outweigh the potential risks of QT prolongation in patients receiving granisetron as concurrent use may increase the risk of QT prolongation. Androgen deprivation therapy may prolong the QT/QTc interval. Granisetron has also been associated with QT prolongation.
Guaifenesin; 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.
Halogenated Anesthetics: (Major) Halogenated anesthetics should be used cautiously and with close monitoring with granisetron. Halogenated anesthetics can prolong the QT interval. Granisetron has been associated with QT prolongation. According to the manufacturer, use of granisetron in patients concurrently treated with drugs known to prolong the QT interval and/or are arrhythmogenic, may result in clinical consequences.
Haloperidol: (Moderate) Caution is advisable when combining haloperidol concurrently 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. Granisetron has been associated with QT prolongation.
Histrelin: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., histrelin) outweigh the potential risks of QT prolongation in patients receiving granisetron as concurrent use may increase the risk of QT prolongation. Androgen deprivation therapy may prolong the QT/QTc interval. Granisetron has also been associated with QT prolongation.
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) According to the manufacturer, caution is warranted when administering granisetron to patients with preexisting electrolyte abnormalities. Patients taking certain diuretics may develop an electrolyte abnormality that may lead to cardiac dysrhythmias and/or QT prolongation. Hypokalemia or hypomagnesemia may occur with administration of potassium-depleting drugs such as loop diuretics and thiazide diuretics, increasing the potential for cardiac arrhythmias.
Hydrochlorothiazide, HCTZ; Methyldopa: (Moderate) According to the manufacturer, caution is warranted when administering granisetron to patients with preexisting electrolyte abnormalities. Patients taking certain diuretics may develop an electrolyte abnormality that may lead to cardiac dysrhythmias and/or QT prolongation. Hypokalemia or hypomagnesemia may occur with administration of potassium-depleting drugs such as loop diuretics and thiazide diuretics, increasing the potential for cardiac arrhythmias.
Hydrochlorothiazide, HCTZ; Moexipril: (Moderate) According to the manufacturer, caution is warranted when administering granisetron to patients with preexisting electrolyte abnormalities. Patients taking certain diuretics may develop an electrolyte abnormality that may lead to cardiac dysrhythmias and/or QT prolongation. Hypokalemia or hypomagnesemia may occur with administration of potassium-depleting drugs such as loop diuretics and thiazide diuretics, increasing the potential for cardiac arrhythmias.
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.
Hydrocodone; Pseudoephedrine: (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) Concomitant use of hydroxychloroquine and granisetron increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Hydroxyzine: (Moderate) Concomitant use of hydroxyzine and granisetron 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 granisetron with other drugs that have serotonergic properties such as methylene blue. If serotonin syndrome is suspected, discontinue granisetron 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) Drugs with a possible risk for QT prolongation and torsade de pointes (TdP), such as ibutilide, should be used cautiously with granisetron. Granisetron has been associated with QT prolongation. According to the manufacturer, use of granisetron in patients concurrently treated with drugs known to prolong the QT interval and/or are arrhythmogenic, may result in clinical consequences. Ibutilide administration can cause QT prolongation and 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 granisetron, a CYP3A substrate, as granisetron toxicities may be significantly increased. The AUC of a sensitive CYP3A substrate was increased 5.4-fold when coadministered with idelalisib.
Iloperidone: (Major) Iloperidone has been associated with QT prolongation; however, torsade de pointes (TdP) has not been reported. According to the manufacturer, since iloperidone may prolong the QT interval, it should be avoided in combination with other agents also known to have this effect, such as granisetron.
Inotuzumab Ozogamicin: (Major) Avoid coadministration of inotuzumab ozogamicin with granisetron 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 at baseline, after treatment initiation, and periodically during therapy as clinically indicated. Both inotuzumab and granisetron have been associated with QT prolongation.
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) According to the manufacturer, caution is warranted when administering granisetron to patients with preexisting electrolyte abnormalities. Patients taking certain diuretics may develop an electrolyte abnormality that may lead to cardiac dysrhythmias and/or QT prolongation. Hypokalemia or hypomagnesemia may occur with administration of potassium-depleting drugs such as loop diuretics and thiazide diuretics, increasing the potential for cardiac arrhythmias.
Isavuconazonium: (Minor) Concomitant use of isavuconazonium with granisetron may result in increased serum concentrations of granisetron. Granisetron 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 granisetron with other drugs that have serotonergic properties such as the 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 granisetron and concurrent serotonergic agents and initiate appropriate medical treatment.
Itraconazole: (Moderate) Use itraconazole with caution in combination with granisetron as concurrent use may increase the risk of QT prolongation. Itraconazole and granisetron have been associated with prolongation of the QT interval.
Ivosidenib: (Major) Avoid coadministration of ivosidenib with granisetron 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. Granisetron has been associated with QT prolongation.
Ketoconazole: (Contraindicated) Avoid concomitant use of ketoconazole and granisetron due to an increased risk for torsade de pointes (TdP) and QT/QTc prolongation.
Lansoprazole; Amoxicillin; Clarithromycin: (Major) Due to an increased risk for QT prolongation and torsade de pointes (TdP), caution is advised when administering clarithromycin with granisetron. Both granisetron and clarithromycin are associated with prolongation of the QT interval, and clarithromycin has also been associated with an established risk for TdP.
Lapatinib: (Moderate) Monitor for evidence of QT prolongation if lapatinib is administered with goserelin; correct electrolyte abnormalities prior to treatment. Granisetron has been associated with QT prolongation. Lapatinib has also been associated with concentration-dependent QT prolongation; ventricular arrhythmias and torsade de pointes (TdP) have been reported in postmarketing experience with lapatinib.
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 granisetron 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. Granisetron has been associated with QT prolongation.
Lenvatinib: (Major) Avoid coadministration of lenvatinib with granisetron due to the risk of QT prolongation. Prolongation of the QT interval has been reported with lenvatinib therapy. Granisetron has also been associated with QT prolongation.
Lesinurad: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of granisetron; monitor for potential reduction in efficacy. Granisetron is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
Lesinurad; Allopurinol: (Moderate) Lesinurad may decrease the systemic exposure and therapeutic efficacy of granisetron; monitor for potential reduction in efficacy. Granisetron is a CYP3A substrate, and lesinurad is a weak CYP3A inducer.
Letermovir: (Moderate) A clinically relevant increase in the plasma concentration of granisetron may occur if given with letermovir. In patients who are also receiving treatment with cyclosporine, the magnitude of this interaction may be amplified. Granisetron is a CYP3A4 substrate. Letermovir is a moderate CYP3A4 inhibitor; however, when given with cyclosporine, the combined effect on CYP3A4 substrates is similar to a strong CYP3A4 inhibitor.
Leuprolide: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving granisetron as concurrent use may increase the risk of QT prolongation. Androgen deprivation therapy may prolong the QT/QTc interval. Granisetron has also been associated with QT prolongation.
Leuprolide; Norethindrone: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., leuprolide) outweigh the potential risks of QT prolongation in patients receiving granisetron as concurrent use may increase the risk of QT prolongation. Androgen deprivation therapy may prolong the QT/QTc interval. Granisetron has also been associated with QT prolongation.
Levofloxacin: (Moderate) Concomitant use of levofloxacin and granisetron 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 granisetron 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 granisetron with other drugs that have serotonergic properties such as levomilnacipran. If serotonin syndrome is suspected, discontinue granisetron 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 granisetron with other drugs that have serotonergic properties such as linezolid. If serotonin syndrome is suspected, discontinue granisetron 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) According to the manufacturer, caution is warranted when administering granisetron to patients with preexisting electrolyte abnormalities. Patients taking certain diuretics may develop an electrolyte abnormality that may lead to cardiac dysrhythmias and/or QT prolongation. Hypokalemia or hypomagnesemia may occur with administration of potassium-depleting drugs such as loop diuretics and thiazide diuretics, increasing the potential for cardiac arrhythmias.
Lithium: (Moderate) Use lithium with caution in combination with granisetron due to the risk of QT prolongation and serotonin syndrome. If serotonin syndrome is suspected, discontinue granisetron and concurrent serotonergic agents and initiate appropriate medical treatment. Both lithium and granisetron have been associated with QT prolongation.
Lofexidine: (Major) Monitor ECG if lofexidine is coadministered with granisetron due to the potential for additive QT prolongation. Lofexidine prolongs the QT interval. In addition, there are postmarketing reports of torsade de pointes. Granisetron has been associated with QT prolongation.
Lonafarnib: (Moderate) Monitor for increased granisetron-related adverse effects, such as gastrointestinal or CNS effects, if coadministration with lonafarnib is necessary. Concurrent use may increase granisetron exposure. Granisetron is a CYP3A4 substrate and lonafarnib is a strong CYP3A4 inhibitor.
Loop diuretics: (Moderate) According to the manufacturer, caution is warranted when administering granisetron to patients with preexisting electrolyte abnormalities. Patients taking certain diuretics may develop an electrolyte abnormality that may lead to cardiac dysrhythmias and/or QT prolongation. Hypokalemia or hypomagnesemia may occur with administration of potassium-depleting drugs such as loop diuretics and thiazide diuretics, increasing the potential for cardiac arrhythmias.
Loperamide: (Moderate) Use granisetron with caution in combination with loperamide due to the risk of QT prolongation. Granisetron has been associated with 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.
Loperamide; Simethicone: (Moderate) Use granisetron with caution in combination with loperamide due to the risk of QT prolongation. Granisetron has been associated with 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.
Lopinavir; Ritonavir: (Major) Avoid coadministration of lopinavir with granisetron due to the potential for additive QT prolongation. If use together is necessary, obtain a baseline ECG to assess initial QT interval and determine frequency of subsequent ECG monitoring, avoid any non-essential QT prolonging drugs, and correct electrolyte imbalances. Both drugs have been associated with QT prolongation. (Minor) Plasma concentrations of granisetron may be elevated when administered concurrently with ritonavir. Clinical monitoring for adverse effects, such as gastrointestinal or CNS effects, is recommended during coadministration. Ritonavir is a CYP3A4 inhibitor; granisetron is a CYP3A4 substrate.
Losartan; Hydrochlorothiazide, HCTZ: (Moderate) According to the manufacturer, caution is warranted when administering granisetron to patients with preexisting electrolyte abnormalities. Patients taking certain diuretics may develop an electrolyte abnormality that may lead to cardiac dysrhythmias and/or QT prolongation. Hypokalemia or hypomagnesemia may occur with administration of potassium-depleting drugs such as loop diuretics and thiazide diuretics, increasing the potential for cardiac arrhythmias.
Macimorelin: (Major) Avoid concurrent administration of macimorelin with drugs that prolong the QT interval, such as granisetron. 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. Granisetron has been associated with QT prolongation.
Maprotiline: (Moderate) Use granisetron with caution in combination with maprotiline due to the risk of QT prolongation and torsade de pointes (TdP). Granisetron has been associated with 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 TdP 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.
Mefloquine: (Moderate) Mefloquine should be used with caution in patients receiving granisetron due to increased risk for QT prolongation and torsade de pointes (TdP). Granisetron has been associated with 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. However, due to the lack of clinical data, mefloquine should be used with caution in patients receiving drugs that prolong the QT interval.
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) Because of the potential risk and severity of serotonin syndrome, use caution and monitor closely when administering methadone with other drugs that have serotonergic properties such as granisetron. 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. If serotonin syndrome is suspected, discontinue granisetron and concurrent serotonergic agents and initiate appropriate medical treatment. In addition, methadone is associated with a risk for QT prolongation and torsade de pointes (TdP), especially at higher doses (> 200 mg/day but averaging approximately 400 mg/day in adult patients). Therefore, methadone should be used cautiously with drugs having a possible risk for QT prolongation and torsade de pointes (TdP) such as granisetron.
Methenamine; Sodium Acid Phosphate; Methylene Blue; Hyoscyamine: (Major) Because of the potential risk and severity of serotonin syndrome, use caution when administering granisetron with other drugs that have serotonergic properties such as methylene blue. If serotonin syndrome is suspected, discontinue granisetron 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.
Methyclothiazide: (Moderate) According to the manufacturer, caution is warranted when administering granisetron to patients with preexisting electrolyte abnormalities. Patients taking certain diuretics may develop an electrolyte abnormality that may lead to cardiac dysrhythmias and/or QT prolongation. Hypokalemia or hypomagnesemia may occur with administration of potassium-depleting drugs such as loop diuretics and thiazide diuretics, increasing the potential for cardiac arrhythmias.
Methylene Blue: (Major) Because of the potential risk and severity of serotonin syndrome, use caution when administering granisetron with other drugs that have serotonergic properties such as methylene blue. If serotonin syndrome is suspected, discontinue granisetron 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) According to the manufacturer, caution is warranted when administering granisetron to patients with preexisting electrolyte abnormalities. Patients taking certain diuretics may develop an electrolyte abnormality that may lead to cardiac dysrhythmias and/or QT prolongation. Hypokalemia or hypomagnesemia may occur with administration of potassium-depleting drugs such as loop diuretics and thiazide diuretics, increasing the potential for cardiac arrhythmias.
Metoprolol; Hydrochlorothiazide, HCTZ: (Moderate) According to the manufacturer, caution is warranted when administering granisetron to patients with preexisting electrolyte abnormalities. Patients taking certain diuretics may develop an electrolyte abnormality that may lead to cardiac dysrhythmias and/or QT prolongation. Hypokalemia or hypomagnesemia may occur with administration of potassium-depleting drugs such as loop diuretics and thiazide diuretics, increasing the potential for cardiac arrhythmias.
Metronidazole: (Moderate) Concomitant use of metronidazole and granisetron 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 granisetron may lead to additive QT interval prolongation. If these drugs are used together, consider electrocardiogram monitoring. In clinical trials, QT prolongation has been reported in patients who received midostaurin as single-agent therapy or in combination with cytarabine and daunorubicin. QT prolongation has been reported with IV and oral granisetron in post-marketing surveillance. In a randomized, single-blind, parallel study of healthy patients treated with the granisetron patch (Sancuso, n = 60) or IV granisetron (10 mcg/kg, n = 60), the baseline corrected QTcF for Sancuso was below 10 milliseconds suggesting no effects on QT prolongation.
Mifepristone: (Major) Concomitant use of granisetron 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.
Milnacipran: (Major) Because of the potential risk and severity of serotonin syndrome, use caution when administering granisetron with other drugs that have serotonergic properties such as milnacipran. If serotonin syndrome is suspected, discontinue granisetron 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.
Mirtazapine: (Moderate) Use caution when using mirtazapine in combination with granistetron as concurrent use may increase the risk of QT prolongation and serotonin syndrome. If serotonin syndrome occurs, all serotonergic agents should be discontinued and appropriate medical treatment should be implemented. 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. Granisetron has been associated with QT prolongation.
Mitotane: (Major) Use caution if mitotane and granisetron are used concomitantly, and monitor for decreased efficacy of granisetron and a possible change in dosage requirements. Mitotane is a strong CYP3A4 inducer and granisetron is a CYP3A4 substrate; coadministration may result in decreased plasma concentrations of granisetron. In a human pharmacokinetic study, hepatic enzyme induction with phenobarbital resulted in a 25% increase in total plasma clearance of IV granisetron; the clinical significance of this change is not known.
Mobocertinib: (Major) Concomitant use of mobocertinib and granisetron 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.
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) Concurrent use of granisetron and moxifloxacin should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Granisetron has been associated with QT prolongation. Moxifloxacin has also been associated with prolongation of the QT interval. Additionally, post-marketing surveillance has identified very rare cases of ventricular arrhythmias including TdP, usually in patients with severe underlying proarrhythmic conditions. The likelihood of QT prolongation may increase with increasing concentrations of moxifloxacin, therefore the recommended dose or infusion rate should not be exceeded.
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 granisetron. Additionally, nilotinib is a moderate inhibitor of CYP3A4 and granisetron is a substrate of CYP3A4; administering these drugs together may result in increased granisetron levels. If the use of granisetron is necessary, hold nilotinib therapy. If these drugs are used together, consider a granisetron dose reduction and monitor patients for toxicity (e.g., QT interval prolongation).
Nirmatrelvir; Ritonavir: (Minor) Plasma concentrations of granisetron may be elevated when administered concurrently with ritonavir. Clinical monitoring for adverse effects, such as gastrointestinal or CNS effects, is recommended during coadministration. Ritonavir is a CYP3A4 inhibitor; granisetron is a CYP3A4 substrate.
Ofloxacin: (Moderate) Concomitant use of ofloxacin and granisetron 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) Use granisetron with caution in combination with olanzapine due to increased risk for QT prolongation and torsade de pointes (TdP). Granisetron has been associated with QT prolongation. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances.
Olanzapine; Fluoxetine: (Moderate) Use fluoxetine with caution in combination with granisteron as there is an increased risk for QT prolongation, torsade de pointes (TdP), and serotonin syndrome. If serotonin syndrome is suspected, discontinue granisetron and concurrent serotonergic agents and initiate appropriate medical treatment. QT prolongation and TdP have been reported in patients treated with fluoxetine. Granisetron has also been associated with QT prolongation. (Moderate) Use granisetron with caution in combination with olanzapine due to increased risk for QT prolongation and torsade de pointes (TdP). Granisetron has been associated with QT prolongation. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances.
Olanzapine; Samidorphan: (Moderate) Use granisetron with caution in combination with olanzapine due to increased risk for QT prolongation and torsade de pointes (TdP). Granisetron has been associated with QT prolongation. Limited data, including some case reports, suggest that olanzapine may be associated with a significant prolongation of the QTc interval in rare instances.
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) According to the manufacturer, caution is warranted when administering granisetron to patients with preexisting electrolyte abnormalities. Patients taking certain diuretics may develop an electrolyte abnormality that may lead to cardiac dysrhythmias and/or QT prolongation. Hypokalemia or hypomagnesemia may occur with administration of potassium-depleting drugs such as loop diuretics and thiazide diuretics, increasing the potential for cardiac arrhythmias.
Olmesartan; Hydrochlorothiazide, HCTZ: (Moderate) According to the manufacturer, caution is warranted when administering granisetron to patients with preexisting electrolyte abnormalities. Patients taking certain diuretics may develop an electrolyte abnormality that may lead to cardiac dysrhythmias and/or QT prolongation. Hypokalemia or hypomagnesemia may occur with administration of potassium-depleting drugs such as loop diuretics and thiazide diuretics, increasing the potential for cardiac arrhythmias.
Ondansetron: (Major) Granisetron has been associated with QT prolongation. According to the manufacturer, use of granisetron in patients concurrently treated with drugs known to prolong the QT interval and/or are arrhythmogenic, may result in clinical consequences. Drugs with a possible risk for QT prolongation and torsade de pointes (TdP) that should be used cautiously and with close monitoring with granisetron include ondansetron. The two drugs are from the same therapeutic class, and would not be expected to be prescribed together. Serotonergic actions of the two drugs might also increase the risk for additive serotonergic side effects.
Oritavancin: (Minor) Granisetron is metabolized by CYP3A4; oritavancin is a weak CYP3A4 inducer. Plasma concentrations and efficacy of granisetron may be reduced if these drugs are administered concurrently.
Osilodrostat: (Moderate) Monitor ECGs in patients receiving osilodrostat with granisetron. Osilodrostat is associated with dose-dependent QT prolongation. Granisetron has been associated with QT prolongation.
Osimertinib: (Major) Avoid coadministration of granisetron 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. Granisetron has also been associated with QT prolongation.
Oxaliplatin: (Major) Monitor electrolytes and ECGs for QT prolongation if coadministration of granisetron with oxaliplatin is necessary; correct electrolyte abnormalities prior to administration of oxaliplatin. Granisetron has been associated with QT prolongation; QT prolongation and ventricular arrhythmias including fatal torsade de pointes have also been reported with oxaliplatin use in postmarketing experience.
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 granisetron 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. Granisetron is a serotonergic drug that has been associated with QT prolongation.
Pacritinib: (Major) Concomitant use of pacritinib and granisetron increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Paliperidone: (Major) Paliperidone has been associated with QT prolongation; torsade de pointes (TdP) and ventricular fibrillation have been reported in the setting of overdose. According to the manufacturer, since paliperidone may prolong the QT interval, it should be avoided in combination with other agents also known to have this effect, such as granisetron. However, if coadministration is necessary and the patient has known risk factors for cardiac disease or arrhythmias, close monitoring is essential.
Panobinostat: (Major) QT prolongation has been reported with panobinostat therapy in patients with multiple myeloma in a clinical trial; use of panobinostat with other agents that prolong the QT interval is not recommended. Obtain an electrocardiogram at baseline and periodically during treatment. Hold panobinostat if the QTcF increases to >= 480 milliseconds during therapy; permanently discontinue if QT prolongation does not resolve. Drugs with a possible risk for QT prolongation and torsade de pointes that should be used cautiously and with close monitoring with panobinostat include granisetron.
Paroxetine: (Major) Because of the potential risk and severity of serotonin syndrome, use caution when administering granisetron with other drugs that have serotonergic properties such as paroxetine. If serotonin syndrome is suspected, discontinue granisetron 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.
Pasireotide: (Moderate) Use granisetron with caution in combination with pasireotide due to increased risk for QT prolongation. Granisetron has been associated with QT prolongation. QT prolongation has occurred with pasireotide at therapeutic and supra-therapeutic doses. Granisetron has been associated with QT prolongation.
Pazopanib: (Major) Coadministration of pazopanib and other drugs that prolong the QT interval is not advised; pazopanib and granisetron have been reported to prolong the QT interval. If pazopanib and granisetron must be continued, closely monitor the patient for QT interval prolongation. In addition, pazopanib is a weak inhibitor of CYP3A4. Coadministration of pazopanib and granisetron, a CYP3A4 substrate, may cause an increase in systemic concentrations of granisetron. Use caution when concurrent administration of granisetron and pazopanib is necessary.
Pentamidine: (Major) Granisetron has been associated with QT prolongation. According to the manufacturer, use of granisetron in patients concurrently treated with drugs known to prolong the QT interval and/or are arrhythmogenic, may result in clinical consequences. Pentamidine has been associated with QT prolongation.
Perphenazine: (Minor) Use granisetron with caution in combination with perphenazine due to increased risk for QT prolongation and torsade de pointes (TdP). Granisetron has been associated with QT prolongation. Perphenazine, a phenothiazine, is associated with a possible risk for QT prolongation.
Perphenazine; Amitriptyline: (Minor) Use granisetron with caution in combination with perphenazine due to increased risk for QT prolongation and torsade de pointes (TdP). Granisetron has been associated with QT prolongation. Perphenazine, a phenothiazine, is associated with a possible risk for QT prolongation.
Phenelzine: (Moderate) Because of the potential risk and severity of serotonin syndrome, use caution when administering granisetron with other drugs that have serotonergic properties such as the 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 granisetron and concurrent serotonergic agents and initiate appropriate medical treatment.
Phenobarbital: (Minor) In a human pharmacokinetic study, hepatic enzyme induction with phenobarbital resulted in an increase in total plasma clearance of intravenous granisetron by 25%. The clinical significance of this change is not known.
Phenobarbital; Hyoscyamine; Atropine; Scopolamine: (Minor) In a human pharmacokinetic study, hepatic enzyme induction with phenobarbital resulted in an increase in total plasma clearance of intravenous granisetron by 25%. The clinical significance of this change is not known.
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 granisetron. Use of granisetron in patients concurrently treated with drugs known to prolong the QT interval and/or are arrhythmogenic, may result in clinical consequences.
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 granisetron with pimozide is contraindicated.
Pitolisant: (Major) Avoid coadministration of pitolisant with granisetron as concurrent use may increase the risk of QT prolongation. Pitolisant prolongs the QT interval. Granisetron has been associated with QT prolongation.
Ponesimod: (Major) In general, do not initiate ponesimod in patients taking granisetron 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. Granisetron has been associated with QT prolongation.
Posaconazole: (Moderate) Use posaconazole with caution in combination with granisetron as concurrent use may increase the risk of QT prolongation. Posaconazole has been associated with prolongation of the QT interval as well as rare cases of torsade de pointes. Granisetron has been associated with QT prolongation.
Primaquine: (Moderate) Use granisetron with caution in combination with primaquine due to increased risk for QT prolongation.
Primidone: (Minor) In a human pharmacokinetic study, hepatic enzyme induction with phenobarbital resulted in a 25% increase in total plasma clearance of intravenous granisetron. The clinical significance of this change is not known. Primidone is the prodrug of phenobarbital and therefore a similar interaction is expected.
Procainamide: (Major) Granisetron should be used cautiously and with close monitoring with Class IA antiarrhythmics (disopyramide, procainamide, and quinidine). Class IA antiarrhythmics are associated with QT prolongation and torsades de pointes (TdP). Granisetron has been associated with QT prolongation. According to the manufacturer, use of granisetron in patients concurrently treated with drugs known to prolong the QT interval and/or are arrhythmogenic, may result in clinical consequences.
Prochlorperazine: (Minor) Use granisetron with caution in combination with prochlorperazine due to increased risk for QT prolongation and torsade de pointes (TdP). Granisetron has been associated with QT prolongation. Theoretically, prochlorperazine may increase the risk of QT prolongation if coadministered with other drugs that have a risk of QT prolongation.
Promethazine: (Moderate) Concomitant use of promethazine and granisetron 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 granisetron 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 granisetron 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 granisetron 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.
Propranolol; Hydrochlorothiazide, HCTZ: (Moderate) According to the manufacturer, caution is warranted when administering granisetron to patients with preexisting electrolyte abnormalities. Patients taking certain diuretics may develop an electrolyte abnormality that may lead to cardiac dysrhythmias and/or QT prolongation. Hypokalemia or hypomagnesemia may occur with administration of potassium-depleting drugs such as loop diuretics and thiazide diuretics, increasing the potential for cardiac arrhythmias.
Quetiapine: (Major) Concomitant use of quetiapine and granisetron 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) According to the manufacturer, caution is warranted when administering granisetron to patients with preexisting electrolyte abnormalities. Patients taking certain diuretics may develop an electrolyte abnormality that may lead to cardiac dysrhythmias and/or QT prolongation. Hypokalemia or hypomagnesemia may occur with administration of potassium-depleting drugs such as loop diuretics and thiazide diuretics, increasing the potential for cardiac arrhythmias.
Quinidine: (Major) Granisetron should be used cautiously and with close monitoring with Class IA antiarrhythmics (disopyramide, procainamide, and quinidine). Class IA antiarrhythmics are associated with QT prolongation and torsades de pointes (TdP). Granisetron has been associated with QT prolongation. According to the manufacturer, use of granisetron in patients concurrently treated with drugs known to prolong the QT interval and/or are arrhythmogenic, may result in clinical consequences.
Quinine: (Major) Concurrent use of quinine and granisetron 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. Granisetron has also been associated with QT prolongation. In addition, concentrations of granisetron may be increased with concomitant use of quinine. Granisetron is a CYP3A4 substrate and quinine is a CYP3A4 inhibitor.
Quizartinib: (Major) Concomitant use of quizartinib and granisetron increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Ranolazine: (Moderate) Use granisetron with caution in combination with ranolazine due to the risk of QT prolongation. Granisetron has been associated with QT prolongation. Ranolazine is associated with dose- and plasma concentration-related increases in the QTc interval. Although there are no studies examining the effects of ranolazine in patients receiving other QT prolonging drugs, coadministration of such drugs may result in additive QT prolongation.
Rasagiline: (Major) Because of the potential risk and severity of serotonin syndrome, use caution when administering granisetron with other drugs that have serotonergic properties such as rasagiline. If serotonin syndrome is suspected, discontinue granisetron 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.
Relugolix: (Moderate) Use granisetron with caution in combination with relugolix due to the risk of QT prolongation. Granisetron has been associated with QT prolongation. Androgen deprivation therapy (i.e., relugolix) may also prolong the QT/QTc interval.
Relugolix; Estradiol; Norethindrone acetate: (Moderate) Use granisetron with caution in combination with relugolix due to the risk of QT prolongation. Granisetron has been associated with QT prolongation. 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 granisetron due to an increased risk for QT prolongation. Ribociclib has been shown to prolong the QT interval in a concentration-dependent manner. Granisetron has also been associated with QT prolongation. Concomitant use may increase the risk for QT prolongation.
Ribociclib; Letrozole: (Major) Avoid coadministration of ribociclib with granisetron due to an increased risk for QT prolongation. Ribociclib has been shown to prolong the QT interval in a concentration-dependent manner. Granisetron has also been associated with QT prolongation. Concomitant use may increase the risk for QT prolongation.
Rifapentine: (Moderate) Monitor for decreased efficacy of granisetron if coadministration with rifapentine is necessary. Concurrent use may decrease granisetron exposure. Granisetron is a CYP3A4 substrate and rifapentine is a strong CYP3A4 inducer. In a human pharmacokinetic study, coadministration with another strong CYP3A4 inducer increased the total plasma clearance of granisetron by 25%. The clinical significance of this change is not known.
Rilpivirine: (Moderate) Use granisetron with caution in combination with rilpivirine due to the risk of QT prolongation. Granisetron has been associated with QT prolongation. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation.
Risperidone: (Moderate) Use risperidone and granisetron together with caution due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Granisetron has been associated with QT prolongation. Risperidone has been associated with a possible risk for QT prolongation and/or TdP, primarily in the overdose setting.
Ritonavir: (Minor) Plasma concentrations of granisetron may be elevated when administered concurrently with ritonavir. Clinical monitoring for adverse effects, such as gastrointestinal or CNS effects, is recommended during coadministration. Ritonavir is a CYP3A4 inhibitor; granisetron is a CYP3A4 substrate.
Romidepsin: (Moderate) Consider monitoring electrolytes and ECGs at baseline and periodically during treatment if romidepsin is administered with granisetron. Romidepsin has been reported to prolong the QT interval. Granisetron has been associated with QT prolongation.
Saquinavir: (Major) Due to a possible risk for QT prolongation and torsade de pointes (TdP), concurrent use of granisetron and saquinavir should be avoided if possible. If no acceptable alternative therapy is available, perform a baseline ECG prior to initiation of concomitant therapy and carefully follow monitoring recommendations. Granisetron has been associated with QT prolongation. According to the manufacturer, use of granisetron with drugs known to prolong the QT interval or are arrhythmogenic, may result in clinical consequences. Saquinavir boosted with ritonavir increases the QT interval in a dose-dependent fashion, which may increase the risk for serious arrhythmias such as TdP.
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 granisetron is necessary due to the risk of additive QT prolongation. Concentration-dependent QT prolongation has been observed with selpercatinib therapy. Granisetron has been associated with QT prolongation.
Sertraline: (Moderate) Use caution and monitor patients for QT prolongation and serotonin syndrome when administering granisetron with sertraline. Granisetron has been associated with QT prolongation. 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 serotinin syndrome. If serotonin syndrome occurs, discontinue serotonergic agents and initiate appropriate medical treatment.
Siponimod: (Major) In general, do not initiate treatment with siponimod in patients receiving granisetron 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. Granisetron has been associated with QT prolongation.
Sodi um Stibogluconate: (Moderate) Concomitant use of sodium stibogluconate and granisetron 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) Use granisetron with caution in combination with solifenacin due to the risk of QT prolongation and torsade de pointes (TdP). Granisetron has been associated with QT prolongation. Solifenacin has been associated with dose-dependent prolongation of the QT interval. Torsades de pointes has been reported with post-marketing use, although causality was not determined.
Sorafenib: (Major) Avoid coadministration of sorafenib with granisetron 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. Both drugs have been associated with QT prolongation.
Sotalol: (Major) Concomitant use of sotalol and granisetron increases the risk of QT/QTc prolongation and torsade de pointes (TdP). Avoid concomitant use if possible, especially in patients with additional risk factors for TdP. Consider taking steps to minimize the risk for QT/QTc interval prolongation and TdP, such as electrolyte monitoring and repletion and ECG monitoring, if concomitant use is necessary.
Spironolactone; Hydrochlorothiazide, HCTZ: (Moderate) According to the manufacturer, caution is warranted when administering granisetron to patients with preexisting electrolyte abnormalities. Patients taking certain diuretics may develop an electrolyte abnormality that may lead to cardiac dysrhythmias and/or QT prolongation. Hypokalemia or hypomagnesemia may occur with administration of potassium-depleting drugs such as loop diuretics and thiazide diuretics, increasing the potential for cardiac arrhythmias.
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) Monitor patients for QT prolongation if coadministration of granisetron with sunitinib is necessary. Sunitinib can cause QT prolongation. Granisetron has also been associated with QT prolongation.
Tacrolimus: (Moderate) Consider ECG and electrolyte monitoring periodically during treatment if tacrolimus is administered with granisetron as concurrent use may increase the risk of QT prolongation. Tacrolimus may prolong the QT interval and cause torsade de pointes (TdP). Granisetron has been associated with QT prolongation.
Tamoxifen: (Moderate) Concomitant use of tamoxifen and granisetron 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) Use granisetron with caution in combination with telavancin due to increased risk for QT prolongation. Both granisetron and telavancin have been associated with QT prolongation.
Telmisartan; Hydrochlorothiazide, HCTZ: (Moderate) According to the manufacturer, caution is warranted when administering granisetron to patients with preexisting electrolyte abnormalities. Patients taking certain diuretics may develop an electrolyte abnormality that may lead to cardiac dysrhythmias and/or QT prolongation. Hypokalemia or hypomagnesemia may occur with administration of potassium-depleting drugs such as loop diuretics and thiazide diuretics, increasing the potential for cardiac arrhythmias.
Tetrabenazine: (Major) Granisetron has been associated with QT prolongation. According to the manufacturer, the use of granisetron in patients concurrently treated with drugs known to prolong the QT interval (e.g., tetrabenazine) and/or are arrhythmogenic, may result in clinical consequences. 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) According to the manufacturer, caution is warranted when administering granisetron to patients with preexisting electrolyte abnormalities. Patients taking certain diuretics may develop an electrolyte abnormality that may lead to cardiac dysrhythmias and/or QT prolongation. Hypokalemia or hypomagnesemia may occur with administration of potassium-depleting drugs such as loop diuretics and thiazide diuretics, increasing the potential for cardiac arrhythmias.
Thioridazine: (Contraindicated) Because of the potential for torsade de pointes (TdP), use of thioridazine with granisetron is contraindicated. Thioridazine is associated with a well-established risk of QT prolongation and TdP; granisetron has also been associated with QT prolongation. Thioridazine 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.
Tolterodine: (Moderate) Use granisetron with caution in combination with tolterodine due to increased risk for QT prolongation and torsade de pointes (TdP). Granisetron has been associated with QT prolongation. Tolterodine has also been associated with dose-dependent prolongation of the QT interval, especially in poor CYP2D6 metabolizers.
Toremifene: (Major) Avoid coadministration of granisetron 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. Granisetron has also been associated with QT prolongation.
Torsemide: (Moderate) According to the manufacturer, caution is warranted when administering granisetron to patients with preexisting electrolyte abnormalities. Patients taking certain diuretics may develop an electrolyte abnormality that may lead to cardiac dysrhythmias and/or QT prolongation. Hypokalemia or hypomagnesemia may occur with administration of potassium-depleting drugs such as loop diuretics and thiazide diuretics, increasing the potential for cardiac arrhythmias.
Tramadol: (Major) Because of the potential risk and severity of serotonin syndrome, use caution when administering granisetron with other drugs that have serotonergic properties such as tramadol. If serotonin syndrome is suspected, discontinue granisetron 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 granisetron with other drugs that have serotonergic properties such as tramadol. If serotonin syndrome is suspected, discontinue granisetron 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.
Tranylcypromine: (Moderate) Because of the potential risk and severity of serotonin syndrome, use caution when administering granisetron with other drugs that have serotonergic properties such as the 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 granisetron and concurrent serotonergic agents and initiate appropriate medical treatment.
Trazodone: (Major) Because trazodone can prolong the QT/QTc interval at therapeutic doses and there are postmarketing reports of torsade de pointes (TdP), the manufacturer of trazodone recommends avoiding use in patients receiving other drugs that increase the QT interval, such as granisetron. In addition, coadministration of trazodone and granisetron may increase the risk of serotonin syndrome. Serotonin syndrome has been reported with both drugs when taken alone, but especially when coadministered with other serotonergic agents. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome. Discontinue granisetron and trazodone and initiate symptomatic treatment if serotonin syndrome occurs.
Triamterene; Hydrochlorothiazide, HCTZ: (Moderate) According to the manufacturer, caution is warranted when administering granisetron to patients with preexisting electrolyte abnormalities. Patients taking certain diuretics may develop an electrolyte abnormality that may lead to cardiac dysrhythmias and/or QT prolongation. Hypokalemia or hypomagnesemia may occur with administration of potassium-depleting drugs such as loop diuretics and thiazide diuretics, increasing the potential for cardiac arrhythmias.
Triclabendazole: (Moderate) Concomitant use of triclabendazole and granisetron 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.
Tricyclic antidepressants: (Moderate) Use granisetron with caution in combination with tricyclic antidepressants due to increased risk for QT prolongation, torsade de pointes (TdP), and serotonin syndrome. Discontinue all serotonergic agents and initiate supportive therapy if serotonin syndrome is suspected. Granisetron has been associated with QT prolongation. Tricyclic antidepressants (TCAs) share pharmacologic properties similar to the Class IA antiarrhythmic agents and may prolong the QT interval, particularly in overdose or with higher-dose prescription therapy (elevated serum concentrations).
Trifluoperazine: (Minor) Use granisetron with caution in combination with trifluoperazine due to increased risk for QT prolongation. Granisetron has been associated with QT prolongation. Trifluoperazine is associated with a possible risk for QT prolongation.
Triptorelin: (Moderate) Consider whether the benefits of androgen deprivation therapy (i.e., triptorelin) outweigh the potential risks of QT prolongation in patients receiving granisetron as concurrent use may increase the risk of QT prolongation. Androgen deprivation therapy may prolong the QT/QTc interval. Granisetron has also been associated with QT prolongation.
Tucatinib: (Moderate) Monitor for increased granisetron-related adverse effects, such as gastrointestinal or CNS effects, if coadministration with tucatinib is necessary. Concurrent use may increase granisetron exposure. Granisetron is a CYP3A4 substrate and tucatinib is a strong CYP3A4 inhibitor.
Valsartan; Hydrochlorothiazide, HCTZ: (Moderate) According to the manufacturer, caution is warranted when administering granisetron to patients with preexisting electrolyte abnormalities. Patients taking certain diuretics may develop an electrolyte abnormality that may lead to cardiac dysrhythmias and/or QT prolongation. Hypokalemia or hypomagnesemia may occur with administration of potassium-depleting drugs such as loop diuretics and thiazide diuretics, increasing the potential for cardiac arrhythmias.
Vandetanib: (Major) Avoid coadministration of vandetanib with granisetron 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. Granisetron has also been associated with QT prolongation.
Vardenafil: (Moderate) Concomitant use of vardenafil and granisetron may increase the risk of QT/QTc prolongation and torsade de pointes (TdP) in some patients. Consider taking steps to minimize the risk of QT/QTc interval prolongation and TdP, such as avoidance, electrolyte monitoring and repletion, and ECG monitoring, especially in patients with additional risk factors for TdP.
Vemurafenib: (Major) Vemurafenib has been associated with QT prolongation. If vemurafenib and another drug, such as granisetron, that is associated with a possible risk for QT prolongation and torsade de pointes (TdP) must be coadministered, ECG monitoring is recommended; closely monitor the patient for QT interval prolongation. Also, vemurafenib is an inducer of CYP3A4 and decreased plasma concentrations of drugs metabolized by this enzyme, such as granisetron, could be expected with concurrent use. Use caution, and monitor therapeutic effects of granisetron when coadministered with vemurafenib.
Venlafaxine: (Moderate) Use granisetron with caution in combination with venlafaxine due to increased risk for QT prolongation and serotonin syndrome. If serotonin syndrome is suspected, discontinue granisetron and concurrent serotonergic agents and initiate appropriate medical treatment. Venlafaxine administration is associated with a possible risk of QT prolongation; torsade de pointes (TdP) has reported with postmarketing use. Granisetron has been associated with QT prolongation.
Vilazodone: (Major) Because of the potential risk and severity of serotonin syndrome, use caution when administering granisetron with other drugs that have serotonergic properties such as vilazodone. If serotonin syndrome is suspected, discontinue granisetron 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 granisetron 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. Granisetron has been associated with QT prolongation.
Vonoprazan; Amoxicillin; Clarithromycin: (Major) Due to an increased risk for QT prolongation and torsade de pointes (TdP), caution is advised when administering clarithromycin with granisetron. Both granisetron and clarithromycin are associated with prolongation of the QT interval, and clarithromycin has also been associated with an established risk for TdP.
Voriconazole: (Moderate) Administer voriconazole with caution in combination with granisetron due to additive QT prolongation. Granisetron has been associated with QT prolongation. Voriconazole has been associated with QT prolongation and rare cases of torsade de pointes.
Vorinostat: (Moderate) Use granisetron with caution in combination with vorinostat due to the risk of QT prolongation. Both granisetron and vorinostat have been associated with QT prolongation.
Vortioxetine: (Moderate) Because of the potential risk and severity of serotonin syndrome, use caution when administering granisetron with other drugs that have serotonergic properties such as vortioxetine. 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. If serotonin syndrome is suspected, discontinue granisetron and concurrent serotonergic agents and initiate appropriate medical treatment.
Ziprasidone: (Major) Concomitant use of ziprasidone and granisetron should be avoided due to the potential for additive QT prolongation. Clinical trial data indicate that ziprasidone causes QT prolongation; there are postmarketing reports of torsade de pointes (TdP) in patients with multiple confounding factors. Granisetron has been associated with QT prolongation.

Granisetron/Granisetron Hydrochloride/Kytril Intravenous Inj Sol: 0.1mg, 1mL, 1mg
Granisetron/Granisetron Hydrochloride/Kytril Oral Tab: 1mg
Sancuso Transdermal Film ER: 3.1mg, 24h
Sustol Subcutaneous Inj Sol: 0.4mL, 10mg

Adults

40 mcg/kg IV; 2 mg PO; 1 transdermal patch; 10 mg subcutaneously.

Geriatric

40 mcg/kg IV; 2 mg PO; 1 transdermal patch; 10 mg subcutaneously.

Adolescents

10 mcg/kg IV is the FDA-approved dosage; up to 40 mcg/kg IV is used off-label. Safety and efficacy have not been established for oral, subcutaneous, or transdermal formulations; however, up to 40 mcg/kg PO twice daily has been used off-label for chemotherapy-induced nausea/vomiting.

Children

2 years and older: 10 mcg/kg IV is the FDA-approved dosage; up to 40 mcg/kg IV is used off-label. Safety and efficacy have not been established for oral, subcutaneous, or transdermal formulations; however, up to 40 mcg/kg PO twice daily has been used off-label for chemotherapy-induced nausea/vomiting. Use of the subcutaneous formulation is not recommended in children under 12 years.
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.

Granisetron may have central and peripheral actions. Granisetron selectively blocks 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 granisetron is mediated centrally, peripherally, or a combination of both remains to be determined. Its affinity for 5-HT3 receptors is 4,000 to 40,000 times higher than for other serotonin receptors. Emesis during chemotherapy appears to be associated with the release of serotonin from enterochromaffin cells in the small intestine, stimulating 5-HT3 receptors. This evokes vagal afferent discharge, inducing vomiting. Blocking these nerve endings in the intestines prevents signals to the central nervous system. Granisetron may antagonize the effects of serotonin on the cholinergic neurons of the colon, slowing colonic transit time.

Granisetron is administered orally, intravenously, subcutaneously, and transdermally. Granisetron distributes freely between plasma and erythrocytes; approximately 65% of the drug is protein bound. There is considerable interpatient variability in the clearance. Approximately 12% of an intravenous dose is eliminated unchanged in the urine in 48 hours; the remainder of a dose is excreted as metabolites in the urine (49%) and the feces (34%).
 
Affected cytochrome P450 isoenzymes: CYP1A1, CYP3A4
Granisetron is metabolized by CYP1A1 and CYP3A4. Granisetron metabolism involves N-demethylation and aromatic ring oxidation followed by conjugation. Animal studies indicate that the metabolites may have pharmacologic activity. Granisetron does not induce or inhibit the cytochrome P450 enzyme system.

Oral Route

Coadministration of granisetron with food decreases the AUC by about 5% and increases the Cmax by about 30% in healthy volunteers. Oral administration results in a half-life of 6.23 hours in normal volunteers; no data are available for the oral half-life in cancer patients.

Intravenous Route

The terminal half-life of granisetron after IV administration is 9 to 12 hours in cancer patients and 5 to 7.7 hours in healthy individuals.

Subcutaneous Route

In healthy subjects, extended-release granisetron is released from the polymer and remains detectable in plasma for 7 days post-dose. A mean concentration of 3.5 ng/mL (range, 0 to 14 ng/mL) was observed at 5 days post-dose. After a single subcutaneous injection (10 mg), the Cmax was 9.8 ng/mL (+/- 4.8 ng/mL) after abdominal administration (n = 113) and 10.8 ng/mL (+/- 4.6 ng/mL) when administered in the upper arm (n = 113); the mean AUC was 680 ng*hour/mL (+/- 362 ng*hour/mL) and 720 ng*hour/mL (+/- 366 ng*hour/mL), respectively. The time to maximum concentration (Tmax) was delayed in patients compared to healthy subjects; in healthy subjects, the mean Tmax was 12 hours (range, 1 to 144 hours) after abdominal administration and 11 hours (range, 1 to 120 hours) when given in the upper arm; in patients, the Tmax was approximately 24 hours. The terminal elimination half-life was approximately 24 hours, and was comparable between healthy subjects and patients.

Topical Route

After transdermal application, granisetron crosses intact skin into systemic circulation by passive diffusion. After a 7-day application of the granisetron patch in healthy subjects (n = 24), a Cmax of 5 ng/mL (CV, 170%) was reached at approximately 48 hours (range, 24 to 168 hours) after patch application; the mean AUC0 to 168 was 527 ng x hour/mL (CV, 173%). Based on the measure of residual content of the patch after removal, approximately 66% (SD, +/- 10.9) of granisetron is delivered from the patch after 7 days. Minimal accumulation of granisetron occurred after consecutive application of two granisetron patches (Sancuso) for 7 days each. The mean plasma concentration at 24 hours after the second patch application was 1.5-told higher due to residual granisetron from the first patch. However, at 48 hours after the second patch was applied, the difference in plasma concentrations decreased (1.3-fold increase compared to the first patch).

Pregnancy

Available published data and postmarketing reports with granisetron in pregnant women have not identified a drug-associated risk of major birth defects, miscarriage, or adverse maternal or fetal outcomes. Granisetron should be used during pregnancy only if the benefit to the mother outweighs the potential risk to the fetus. In a published ex vivo human placental perfusion model, no transplacental passage of granisetron was detected at a concentration (5 ng/mL) that mimics the plasma concentration achieved following transdermal application of granisetron. In animal reproduction studies, no adverse developmental effects were observed in pregnant rats and rabbits administered granisetron during organogenesis at intravenous doses up to 24 times and 16 times, respectively, the maximum recommended human dose delivered by the granisetron patch, based on body surface area. Some formulations of granisetron injection contain benzyl alcohol; benzyl alcohol is known to cross the placenta and may pose a risk to the fetus or newborn. Evidence is limited on the safety or efficacy of the serotonin 5-HT3 inhibitors for treating nausea and vomiting of pregnancy. Alternatives in this class to granisetron exist for consideration for use during pregnancy, due to more published data in this population. The American College of Obstetricians and Gynecologists (ACOG) include ondansetron as a third-line pharmacologic treatment option for nausea and vomiting of pregnancy in patients who have failed other therapies.

It is not known whether granisetron is excreted in human milk. However, due to its low molecular weight, transfer into breast milk should be expected. Caution should be exercised when administering granisetron 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.