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  • CLASSES

    Serotonin/5HT3 Antagonist Antiemetics/antinauseants

    DEA CLASS

    Rx

    DESCRIPTION

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

    COMMON BRAND NAMES

    Kytril, Sancuso, Sustol

    HOW SUPPLIED

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

    DOSAGE & INDICATIONS

    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 24 to 48 hours before chemotherapy. The patch may be worn for up to 7 days depending on the duration of chemotherapy. Remove the patch no sooner than 24 hours after chemotherapy. Total dose of granisetron in each patch is 34.3 mg.

    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 2 years and older and Adolescents

    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 2 years and older† and Adolescents†

    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

    MAXIMUM DOSAGE

    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.
    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.

    DOSING CONSIDERATIONS

    Hepatic Impairment

    Specific guidelines for dosage adjustments in hepatic impairment are not available; it appears that no dosage adjustments are needed.

    Renal Impairment

    Dosage Adjustments for Baseline Renal Impairment
    Granisetron Extended-Release Injection:
    Moderate renal impairment (CrCL 30 to 59 mL/min): Do not administer more frequently than every 14 days.
    Severe renal impairment (CrCL less than 30 mL/min): Avoid use of granisetron extended-release.
    Granisetron Injection, Tablets, Oral Solution, and Patch: Dosage adjustments are not necessary.

    ADMINISTRATION

    Oral Administration
    Oral Solid Formulations

    Oral tablets: When taken with food, the AUC is decreased by 5% and the Cmax is increased by 30%.

    Oral Liquid Formulations

    Oral solution: Measure dose with a calibrated oral syringe or other calibrated container.

    Injectable Administration

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

    Intravenous Administration

    Contains benzoyl alcohol as a preservative.
    Administer 30 minutes before the administration of chemotherapy.
    Intravenous injection:
    May be given undiluted over 30 seconds via Y-site.
    Intravenous infusion:
    Prepare IV infusion at time of administration. Dilute dose in 5% Dextrose injection or 0.9% Sodium Chloride injection to a total volume of 20 to 50 mL.
    Infuse IV over 5 minutes.
    Dilute granisetron has been shown to be stable for at least 24 hours when diluted in 5% Dextrose injection or 0.9% Sodium Chloride injection and stored at room temperature under normal lighting conditions.

    Subcutaneous Administration

    Extended-release granisetron (Sustol) 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 (Sustol):
    Remove the extended-release granisetron kit from the refrigerator at least 60 minutes prior to administration; all contents should warm to room temperature.
    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.
     
    Administration of extended-release granisetron (Sustol):
    Complete administration instructions with illustrations are available in the extended-release granisetron kit.
    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

    Each granisetron transdermal system is adhered to a rigid plastic film and a separate clear protective liner. Remove the clear protective liner revealing the printed side of the patch. The unprinted, sticky side of the patch is covered by a rigid plastic film. Bend the patch in the middle to allow removal of the plastic film and application of the patch. Do not cut the patch.
    Apply patch to clean, dry, intact healthy skin on the upper outer arm immediately after the pouch has been opened; do not place on skin that is red, irritated, or damaged. Apply 24 to 48 hours before chemotherapy, and remove a minimum of 24 hours after completion of chemotherapy. The patch can be worn for up to 7 days.

    STORAGE

    Granisol:
    - Protect from light
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    Kytril:
    - Discard penetrated multi-dose vial after 30 days
    - Do not freeze
    - Protect from light
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    - Store in carton until time of use
    Sancuso:
    - Store between 68 to 77 degrees F, excursions permitted 59 to 86 degrees F
    - Store in original package until time of use
    Sustol:
    - Discard product if it contains particulate matter, is cloudy, or discolored
    - Do not freeze
    - Protect from light
    - Refrigerate (between 36 and 46 degrees F)
    - Store at temperatures not exceeding 77 degrees F for no more than 7 days if refrigeration is not available

    CONTRAINDICATIONS / PRECAUTIONS

    Dolasetron hypersensitivity, granisetron hypersensitivity, ondansetron hypersensitivity, palonosetron hypersensitivity

    Granisetron should be avoided in patients with known or suspected granisetron hypersensitivity or to any inactive ingredients of the product; extended-release granisetron (Sustol) is also contraindicated in patients with ondansetron hypersensitivity, palonosetron hypersensitivity or dolasetron hypersensitivity. Regular-release granisetron should be used with caution in patients with hypersensitivity to other serotonin antagonists or similar drugs; cross sensitivity may be seen between these agents. Hypersensitivity reactions including anaphylaxis have been reported in granisetron-treated patients who have reported hypersensitivities to other serotonin antagonists. These reactions may occur up to 7 days or longer after administration of extended-release granisetron and may have an extended course. Inform patients of the signs and symptoms of anaphylaxis and instruct them to seek immediate medical care should they occur. If hypersensitivity reactions occur, administer appropriate treatment and monitor until signs and symptoms resolve.

    Benzyl alcohol hypersensitivity, neonates

    Some formulations of granisetron regular-release injection are formulated with benzyl alcohol, and should be avoided in patients with benzyl alcohol hypersensitivity. Granisetron injection that contains benzyl alcohol should be avoided in neonates. Exposure to large amounts of benzyl alcohol has been associated with 'gasping syndrome,' a potentially fatal condition characterized by metabolic acidosis and CNS, respiratory, circulatory, and renal dysfunction.

    Constipation, GI obstruction, ileus, surgery

    The use of granisetron in patients after abdominal surgery or in patients with chemotherapy-induced nausea and vomiting may mask a progressive ileus, GI obstruction, and/or gastric distension. Monitor patients for the development of constipation and decreased bowel activity, and consider optimizing bowel regimens; in patients receiving extended-release granisetron, drug may be released over at least 5 to 7 days.

    Sunlight (UV) exposure

    Granisetron may be degraded by direct natural or artificial sunlight. Due to a potential skin reaction, if there is a risk of sunlight (UV) exposure, patients wearing the granisetron patch should cover it with clothing during the period of wear and for 10 days after its removal.

    Alcoholism, bradycardia, cardiac arrhythmias, cardiac disease, coronary artery disease, diabetes mellitus, females, geriatric, heart failure, hypertension, hypocalcemia, hypokalemia, hypomagnesemia, long QT syndrome, malnutrition, myocardial infarction, QT prolongation, thyroid disease

    Although not adequately studied, QT prolongation has been reported after granisetron administration; data demonstrate that ECG interval changes are a class effect of the 5-HT(3) receptor antagonists. Use granisetron with caution in patients with cardiac disease or other conditions that may increase the risk of QT prolongation including cardiac arrhythmias, congenital long QT syndrome, heart failure, bradycardia, myocardial infarction, hypertension, coronary artery disease, hypomagnesemia, hypokalemia, hypocalcemia, or in patients receiving medications known to prolong the QT interval or cause electrolyte imbalances. Females, geriatric patients, patients with diabetes mellitus, thyroid disease, malnutrition, alcoholism, or hepatic dysfunction may also be at increased risk for QT prolongation. However, the theoretical concern regarding cardiovascular adverse events with these agents is not supported by clinical experience. The clinically significant benefits of these agents appear to outweigh the theoretically small risk of meaningful cardiovascular events; however, the risks and benefits should be determined for each individual patient.

    Bipolar disorder, depression, pain

    The development of serotonin syndrome, including some fatalities, has been reported with 5HT3-receptor antagonists. Most reports have been associated with concomitant use of serotonergic drugs (e.g., selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), monoamine oxidase inhibitors, mirtazapine, fentanyl, lithium, tramadol, and IV methylene blue), and have occurred in a post-anesthesia care unit or an infusion center. Patients with depression, bipolar disorder, or pain disorders may be at increased risk due to concomitant medications. Monitor patients for symptoms associated with serotonin syndrome, including metal status changes (e.g., agitation, hallucinations, delirium, and coma), autonomic instability (e.g., tachycardia, labile blood pressure, dizziness, diaphoresis, flushing, hyperthermia), neuromuscular symptoms (e.g., tremor, rigidity, myoclonus, hyperreflexia, incoordination), seizures. If symptoms occur, discontinue granisetron and initiate supportive care.

    Heating pad

    Heat exposure increases plasma concentrations of granisetron from the Sancuso patch. Patients should avoid prolonged exposure to external heat sources, such as a heating pad or electric blanket, in the vicinity of the Sancuso patch.

    Anticoagulant therapy, bleeding

    Use caution if treatment with extended-release granisetron is necessary in patients receiving concomitant anticoagulant therapy or antiplatelet therapy, as there is an increased risk of bruising or severe (greater than 4 cm) hematoma. Injection site reactions have been reported in patients receiving extended-release granisetron; some injection site reactions may occur up to 2 weeks or more after administration. Bleeding, in some cases prolonged, has also been reported and required emergency management in one patient. In patients with ongoing or unresolved injection-site reactions, administer extended-release granisetron at a site away from the areas affected.

    Pregnancy

    There are no available data on the use of granisetron in pregnant women; however, animal studies have revealed no teratogenic effects. Granisetron injection, patch, and oral formulations are classified as FDA pregnancy risk category B. It is not known if granisetron crosses the placenta; however, due to its low molecular weight, passage across the placental barrier is expected. Some formulations of granisetron injection contain benzyl alcohol which may cross the placenta and could result in untoward adverse events in the newly born neonate. Granisetron should be used during pregnancy only if the benefit to the mother outweighs the potential risk to the fetus. Other alternatives exist. When necessary, the American College of Obstetricians and Gynecologists recommends the use of ondansetron for the treatment of nausea and vomiting of pregnancy in patients who are dehydrated, requiring IV fluid replacement, and have failed other therapies.

    Breast-feeding

    According to the manufacturer, 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. If a breast-feeding infant experiences an adverse effect related to a maternally administered drug, healthcare providers are encouraged to report the adverse effect to the FDA.

    ADVERSE REACTIONS

    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
    ileus / Delayed / Incidence not known
    GI obstruction / 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 / 0.7-21.0
    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
    insomnia / Early / 0-5.0
    dizziness / Early / 3.0-5.0
    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
    agitation / Early / 0-2.0
    anxiety / Delayed / 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

    DRUG INTERACTIONS

    Acetaminophen; Butalbital; Caffeine; Codeine: (Moderate) Serotonin syndrome can occur during concomitant use of opiate agonists with serotonergic drugs, such as serotonin-receptor antagonists. Symptoms may occur hours to days after concomitant use, particularly after dose increases. Serotonin syndrome may occur within recommended dose ranges. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Acetaminophen; Codeine: (Moderate) Serotonin syndrome can occur during concomitant use of opiate agonists with serotonergic drugs, such as serotonin-receptor antagonists. Symptoms may occur hours to days after concomitant use, particularly after dose increases. Serotonin syndrome may occur within recommended dose ranges. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Acetaminophen; Hydrocodone: (Moderate) Serotonin syndrome can occur during concomitant use of opiate agonists with serotonergic drugs, such as serotonin-receptor antagonists. Symptoms may occur hours to days after concomitant use, particularly after dose increases. Serotonin syndrome may occur within recommended dose ranges. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Acetaminophen; Oxycodone: (Moderate) Serotonin syndrome can occur during concomitant use of opiate agonists with serotonergic drugs, such as serotonin-receptor antagonists. Symptoms may occur hours to days after concomitant use, particularly after dose increases. Serotonin syndrome may occur within recommended dose ranges. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Acetaminophen; 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.
    Aclidinium; Formoterol: (Moderate) Use granisetron with caution in combination with long-acting beta-agonists due to the risk of QT prolongation. Granisetron has been associated with QT prolongation. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Albuterol: (Minor) Use granisetron with caution in combination with short-acting beta-agonists due to the risk of QT prolongation. Granisetron has been associated with QT prolongation. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Albuterol; Ipratropium: (Minor) Use granisetron with caution in combination with short-acting beta-agonists due to the risk of QT prolongation. Granisetron has been associated with QT prolongation. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    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; 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.
    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.
    Amlodipine; Hydrochlorothiazide, HCTZ; Olmesartan: (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.
    Amlodipine; Hydrochlorothiazide, HCTZ; Valsartan: (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; Lansoprazole: (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.
    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: (Severe) 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, dolasetron and ondansetron may cause additive QT prolongation with apomorphine.
    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.
    Arformoterol: (Moderate) Use granisetron with caution in combination with long-acting beta-agonists due to the risk of QT prolongation. Granisetron has been associated with QT prolongation. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Aripiprazole: (Moderate) Use granisetron with caution in combination with apriprazole due to the risk of QT prolongation. Granisetron has been associated with QT prolongation. QT prolongation has occurred during therapeutic use of aripiprazole and following overdose.
    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; Butalbital; Caffeine; Codeine: (Moderate) Serotonin syndrome can occur during concomitant use of opiate agonists with serotonergic drugs, such as serotonin-receptor antagonists. Symptoms may occur hours to days after concomitant use, particularly after dose increases. Serotonin syndrome may occur within recommended dose ranges. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Aspirin, ASA; Carisoprodol; Codeine: (Moderate) Serotonin syndrome can occur during concomitant use of opiate agonists with serotonergic drugs, such as serotonin-receptor antagonists. Symptoms may occur hours to days after concomitant use, particularly after dose increases. Serotonin syndrome may occur within recommended dose ranges. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Aspirin, ASA; Oxycodone: (Moderate) Serotonin syndrome can occur during concomitant use of opiate agonists with serotonergic drugs, such as serotonin-receptor antagonists. Symptoms may occur hours to days after concomitant use, particularly after dose increases. Serotonin syndrome may occur within recommended dose ranges. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome. 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) Use granisetron with caution in combination with atomoxetine due to the risk of QT prolongation. Granisetron has been associated with QT prolongation. QT prolongation has occurred during therapeutic use of atomoxetine and following overdose.
    Atropine; 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.
    Atropine; Hyoscyamine; Phenobarbital; 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.
    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: (Moderate) Use granisetron with caution in combination with azithromycin due to the risk of QT prolongation. Granisetron has been associated with QT prolongation. QT prolongation and torsade de pointes (TdP) have been spontaneously reported during azithromycin postmarketing surveillance.
    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.
    Belladonna Alkaloids; Ergotamine; 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.
    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.
    Bendroflumethiazide; Nadolol: (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) Careful monitoring, particularly during treatment initiation and dose adjustment, is recommended during coadministration of benzhydrocodone and Serotonin-Receptor Antagonists because of the potential risk of serotonin syndrome. Discontinue benzhydrocodone if serotonin syndrome is suspected. 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. Serotonin syndrome, in its most severe form, can resemble neuroleptic malignant syndrome.
    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.
    Bepridil: (Severe) 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. Because of the potential for torsade de pointes (TdP), use of bepridil with granisetron is contraindicated.
    Bismuth Subcitrate Potassium; Metronidazole; Tetracycline: (Moderate) Use granisetron with caution in combination with metronidazole due to the risk of QT prolongation. Potential QT prolongation has been reported in limited case reports with metronidazole. Granisetron has been associated with QT prolongation.
    Bismuth Subsalicylate; Metronidazole; Tetracycline: (Moderate) Use granisetron with caution in combination with metronidazole due to the risk of QT prolongation. Potential QT prolongation has been reported in limited case reports with metronidazole. Granisetron has been associated with QT prolongation.
    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.
    Boceprevir: (Moderate) Close clinical monitoring is advised when administering granisetron with boceprevir due to an increased potential for granisetron-related adverse events. If granisetron dose adjustments are made, re-adjust the dose upon completion of boceprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of granisetron. Granisetron is metabolized by the hepatic isoenzyme CYP3A4; boceprevir inhibits this isoenzyme. Coadministration may result in elevated granisetron plasma concentrations.
    Brompheniramine; Guaifenesin; Hydrocodone: (Moderate) Serotonin syndrome can occur during concomitant use of opiate agonists with serotonergic drugs, such as serotonin-receptor antagonists. Symptoms may occur hours to days after concomitant use, particularly after dose increases. Serotonin syndrome may occur within recommended dose ranges. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Brompheniramine; Hydrocodone; Pseudoephedrine: (Moderate) Serotonin syndrome can occur during concomitant use of opiate agonists with serotonergic drugs, such as serotonin-receptor antagonists. Symptoms may occur hours to days after concomitant use, particularly after dose increases. Serotonin syndrome may occur within recommended dose ranges. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Budesonide; Formoterol: (Moderate) Use granisetron with caution in combination with long-acting beta-agonists due to the risk of QT prolongation. Granisetron has been associated with QT prolongation. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    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.
    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.
    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.
    Carbinoxamine; Hydrocodone; Phenylephrine: (Moderate) Serotonin syndrome can occur during concomitant use of opiate agonists with serotonergic drugs, such as serotonin-receptor antagonists. Symptoms may occur hours to days after concomitant use, particularly after dose increases. Serotonin syndrome may occur within recommended dose ranges. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Carbinoxamine; Hydrocodone; Pseudoephedrine: (Moderate) Serotonin syndrome can occur during concomitant use of opiate agonists with serotonergic drugs, such as serotonin-receptor antagonists. Symptoms may occur hours to days after concomitant use, particularly after dose increases. Serotonin syndrome may occur within recommended dose ranges. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    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 if possible, due to the risk of QT prolongation and torsade de pointes (TdP). Chloroquine administration is associated with an increased risk of QT prolongation and TdP. Granisetron has also been associated with QT prolongation. Coadministration may further increase the risk of QT prolongation and torsade de pointes.
    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) Serotonin syndrome can occur during concomitant use of opiate agonists with serotonergic drugs, such as serotonin-receptor antagonists. Symptoms may occur hours to days after concomitant use, particularly after dose increases. Serotonin syndrome may occur within recommended dose ranges. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Chlorpheniramine; Guaifenesin; Hydrocodone; Pseudoephedrine: (Moderate) Serotonin syndrome can occur during concomitant use of opiate agonists with serotonergic drugs, such as serotonin-receptor antagonists. Symptoms may occur hours to days after concomitant use, particularly after dose increases. Serotonin syndrome may occur within recommended dose ranges. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Chlorpheniramine; Hydrocodone: (Moderate) Serotonin syndrome can occur during concomitant use of opiate agonists with serotonergic drugs, such as serotonin-receptor antagonists. Symptoms may occur hours to days after concomitant use, particularly after dose increases. Serotonin syndrome may occur within recommended dose ranges. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Chlorpheniramine; Hydrocodone; Phenylephrine: (Moderate) Serotonin syndrome can occur during concomitant use of opiate agonists with serotonergic drugs, such as serotonin-receptor antagonists. Symptoms may occur hours to days after concomitant use, particularly after dose increases. Serotonin syndrome may occur within recommended dose ranges. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Chlorpheniramine; Hydrocodone; Pseudoephedrine: (Moderate) Serotonin syndrome can occur during concomitant use of opiate agonists with serotonergic drugs, such as serotonin-receptor antagonists. Symptoms may occur hours to days after concomitant use, particularly after dose increases. Serotonin syndrome may occur within recommended dose ranges. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome. 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) Use granisetron with caution in combination with ciprofloxacin due to the risk of QT prolongation. Rare cases of QT prolongation and torsade de pointes (TdP) have been reported with ciprofloxacin during postmarketing surveillance. Granisetron has been associated with QT prolongation.
    Cisapride: (Severe) 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: (Major) Monitor ECGs for QT prolongation when clofazimine is administered with granisetron. QT prolongation and torsade de pointes have been reported in patients receiving clofazimine in combination with QT prolonging medications. Granisetron has been associated with QT prolongation.
    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) Serotonin syndrome can occur during concomitant use of opiate agonists with serotonergic drugs, such as serotonin-receptor antagonists. Symptoms may occur hours to days after concomitant use, particularly after dose increases. Serotonin syndrome may occur within recommended dose ranges. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Codeine; Guaifenesin: (Moderate) Serotonin syndrome can occur during concomitant use of opiate agonists with serotonergic drugs, such as serotonin-receptor antagonists. Symptoms may occur hours to days after concomitant use, particularly after dose increases. Serotonin syndrome may occur within recommended dose ranges. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Codeine; Phenylephrine; Promethazine: (Moderate) Serotonin syndrome can occur during concomitant use of opiate agonists with serotonergic drugs, such as serotonin-receptor antagonists. Symptoms may occur hours to days after concomitant use, particularly after dose increases. Serotonin syndrome may occur within recommended dose ranges. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. (Moderate) Use granisetron with caution in combination with promethazine due to increased risk for QT prolongation and torsade de pointes (TdP). Granisetron has been associated with QT prolongation. Promethazine, a phenothiazine, is associated with a possible risk for QT prolongation.
    Codeine; Promethazine: (Moderate) Serotonin syndrome can occur during concomitant use of opiate agonists with serotonergic drugs, such as serotonin-receptor antagonists. Symptoms may occur hours to days after concomitant use, particularly after dose increases. Serotonin syndrome may occur within recommended dose ranges. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs. (Moderate) Use granisetron with caution in combination with promethazine due to increased risk for QT prolongation and torsade de pointes (TdP). Granisetron has been associated with QT prolongation. Promethazine, a phenothiazine, is associated with a possible risk for QT prolongation.
    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.
    Dasabuvir; Ombitasvir; Paritaprevir; 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.
    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) For patients taking a deutetrabenazine dosage more than 24 mg/day with granisetron, assess the QTc interval before and after increasing the dosage of either medication as concurrent use may increase the risk of QT prolongation. Clinically relevant QTc prolongation may occur with deutetrabenazine. Granisetron has been associated with QT prolongation.
    Dextromethorphan; Promethazine: (Moderate) Use granisetron with caution in combination with promethazine due to increased risk for QT prolongation and torsade de pointes (TdP). Granisetron has been associated with QT prolongation. Promethazine, a phenothiazine, is associated with a possible risk for QT prolongation.
    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.
    Diphenhydramine; Hydrocodone; Phenylephrine: (Moderate) Serotonin syndrome can occur during concomitant use of opiate agonists with serotonergic drugs, such as serotonin-receptor antagonists. Symptoms may occur hours to days after concomitant use, particularly after dose increases. Serotonin syndrome may occur within recommended dose ranges. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    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: (Severe) 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: (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.
    Erythromycin; Sulfisoxazole: (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) Use escitalopram with caution in combination with granisetron as concurrent use may increase the risk of QT prolongation. Escitalopram has been associated with a risk of QT prolongation and torsade de pointes (TdP). Granisetron has been associated with QT prolongation.
    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.
    Ezogabine: (Moderate) Use granisetron with caution in combination with ezogabine due to the risk of QT prolongation, as both drugs have been associated with QT prolongation.
    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) Use fluconazole with caution in combination with granisetron as concurrent use may increase the risk of QT prolongation. Granisetron has been associated with QT prolongation. Fluconazole has been associated with QT prolongation and rare cases of torsade de pointes (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.
    Fluoxetine; Olanzapine: (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.
    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.
    Fluticasone; Salmeterol: (Moderate) Use granisetron with caution in combination with long-acting beta-agonists due to the risk of QT prolongation. Granisetron has been associated with QT prolongation. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Fluticasone; Umeclidinium; Vilanterol: (Moderate) Use granisetron with caution in combination with long-acting beta-agonists due to the risk of QT prolongation. Granisetron has been associated with QT prolongation. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Fluticasone; Vilanterol: (Moderate) Use granisetron with caution in combination with long-acting beta-agonists due to the risk of QT prolongation. Granisetron has been associated with QT prolongation. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    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.
    Formoterol: (Moderate) Use granisetron with caution in combination with long-acting beta-agonists due to the risk of QT prolongation. Granisetron has been associated with QT prolongation. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Formoterol; Mometasone: (Moderate) Use granisetron with caution in combination with long-acting beta-agonists due to the risk of QT prolongation. Granisetron has been associated with QT prolongation. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    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.
    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.
    Glycopyrrolate; Formoterol: (Moderate) Use granisetron with caution in combination with long-acting beta-agonists due to the risk of QT prolongation. Granisetron has been associated with QT prolongation. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    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) Serotonin syndrome can occur during concomitant use of opiate agonists with serotonergic drugs, such as serotonin-receptor antagonists. Symptoms may occur hours to days after concomitant use, particularly after dose increases. Serotonin syndrome may occur within recommended dose ranges. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Guaifenesin; Hydrocodone; Pseudoephedrine: (Moderate) Serotonin syndrome can occur during concomitant use of opiate agonists with serotonergic drugs, such as serotonin-receptor antagonists. Symptoms may occur hours to days after concomitant use, particularly after dose increases. Serotonin syndrome may occur within recommended dose ranges. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome. 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) Serotonin syndrome can occur during concomitant use of opiate agonists with serotonergic drugs, such as serotonin-receptor antagonists. Symptoms may occur hours to days after concomitant use, particularly after dose increases. Serotonin syndrome may occur within recommended dose ranges. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Hydralazine; 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: (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; Irbesartan: (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; Lisinopril: (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; Losartan: (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; Metoprolol: (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.
    Hydrochlorothiazide, HCTZ; Olmesartan: (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; Propranolol: (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; Quinapril: (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; Spironolactone: (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; Telmisartan: (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; Triamterene: (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; Valsartan: (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) Serotonin syndrome can occur during concomitant use of opiate agonists with serotonergic drugs, such as serotonin-receptor antagonists. Symptoms may occur hours to days after concomitant use, particularly after dose increases. Serotonin syndrome may occur within recommended dose ranges. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Hydrocodone; Ibuprofen: (Moderate) Serotonin syndrome can occur during concomitant use of opiate agonists with serotonergic drugs, such as serotonin-receptor antagonists. Symptoms may occur hours to days after concomitant use, particularly after dose increases. Serotonin syndrome may occur within recommended dose ranges. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Hydrocodone; Phenylephrine: (Moderate) Serotonin syndrome can occur during concomitant use of opiate agonists with serotonergic drugs, such as serotonin-receptor antagonists. Symptoms may occur hours to days after concomitant use, particularly after dose increases. Serotonin syndrome may occur within recommended dose ranges. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Hydrocodone; Potassium Guaiacolsulfonate: (Moderate) Serotonin syndrome can occur during concomitant use of opiate agonists with serotonergic drugs, such as serotonin-receptor antagonists. Symptoms may occur hours to days after concomitant use, particularly after dose increases. Serotonin syndrome may occur within recommended dose ranges. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Hydrocodone; Potassium Guaiacolsulfonate; Pseudoephedrine: (Moderate) Serotonin syndrome can occur during concomitant use of opiate agonists with serotonergic drugs, such as serotonin-receptor antagonists. Symptoms may occur hours to days after concomitant use, particularly after dose increases. Serotonin syndrome may occur within recommended dose ranges. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Hydrocodone; Pseudoephedrine: (Moderate) Serotonin syndrome can occur during concomitant use of opiate agonists with serotonergic drugs, such as serotonin-receptor antagonists. Symptoms may occur hours to days after concomitant use, particularly after dose increases. Serotonin syndrome may occur within recommended dose ranges. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Hydroxychloroquine: (Major) Avoid coadministration of hydroxychloroquine and granisetron. Hydroxychloroquine increases the QT interval and should not be administered with other drugs known to prolong the QT interval. Ventricular arrhythmias and torsade de pointes have been reported with the use of hydroxychloroquine. Granisetron has been associated with QT prolongation.
    Hydroxyzine: (Moderate) Caution is recommended if hydroxyzine is administered with granisetron due to the potential for additive QT prolongation and risk of torsade de pointes (TdP). Postmarketing data indicate that hydroxyzine causes QT prolongation and TdP. Granisetron has been associated with QT prolongation.
    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) Serotonin syndrome can occur during concomitant use of opiate agonists with serotonergic drugs, such as serotonin-receptor antagonists. Symptoms may occur hours to days after concomitant use, particularly after dose increases. Serotonin syndrome may occur within recommended dose ranges. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome. 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.
    Indacaterol: (Moderate) Use granisetron with caution in combination with long-acting beta-agonists due to the risk of QT prolongation. Granisetron has been associated with QT prolongation. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Indacaterol; Glycopyrrolate: (Moderate) Use granisetron with caution in combination with long-acting beta-agonists due to the risk of QT prolongation. Granisetron has been associated with QT prolongation. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    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.
    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: (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 isocarboxazid. 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.
    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: (Moderate) Use ketoconazole with caution in combination with granisetron as concurrent use may increase the risk of QT prolongation. Ketoconazole and granisetron have been associated with prolongation of the QT interval.
    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.
    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.
    Levalbuterol: (Minor) Use granisetron with caution in combination with short-acting beta-agonists due to the risk of QT prolongation. Granisetron has been associated with QT prolongation. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Levofloxacin: (Moderate) Use granisetron with caution in combination with levofloxacin. Granisetron has been associated with QT prolongation. Levofloxacin has been associated with a risk of QT prolongation and torsade de pointes (TdP). Although extremely rare, TdP has been reported during postmarketing surveillance of levofloxacin.
    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.
    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.
    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.
    Long-acting beta-agonists: (Moderate) Use granisetron with caution in combination with long-acting beta-agonists due to the risk of QT prolongation. Granisetron has been associated with QT prolongation. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    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) Due to the potential for QT prolongation and torsade de pointes, caution is advised when administering lopinavir; ritonavir with granisetron. Both lopinavir; ritonavir and granisetron are associated with prolongation of the QT interval. In addition, lopinavir; ritonavir inhibits CYP3A4 and granisetron is a CYP3A substrate. Coadministration may increase the serum concentrations of granisetron. (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.
    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; Promethazine: (Moderate) Use granisetron with caution in combination with promethazine due to increased risk for QT prolongation and torsade de pointes (TdP). Granisetron has been associated with QT prolongation. Promethazine, a phenothiazine, is associated with a possible risk for QT prolongation.
    Mesoridazine: (Severe) 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., mesoridazine) and/or are arrhythmogenic, may result in clinical consequences.
    Metaproterenol: (Minor) Use granisetron with caution in combination with short-acting beta-agonists due to the risk of QT prolongation. Granisetron has been associated with QT prolongation. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    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.
    Metronidazole: (Moderate) Use granisetron with caution in combination with metronidazole due to the risk of QT prolongation. Potential QT prolongation has been reported in limited case reports with metronidazole. Granisetron has been associated with QT prolongation.
    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) Due to a possible risk for QT prolongation and torsade de pointes (TdP), mifepristone and granisetron should be used together cautiously. Mifepristone has been associated with dose-dependent prolongation of the QT interval. There is no experience with high exposure or concomitant use with other QT prolonging drugs. To minimize the risk of QT prolongation, the lowest effective dose should always be used. 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.
    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.
    Morphine: (Moderate) Serotonin syndrome can occur during concomitant use of opiate agonists with serotonergic drugs, such as serotonin-receptor antagonists. Symptoms may occur hours to days after concomitant use, particularly after dose increases. Serotonin syndrome may occur within recommended dose ranges. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    Morphine; Naltrexone: (Moderate) Serotonin syndrome can occur during concomitant use of opiate agonists with serotonergic drugs, such as serotonin-receptor antagonists. Symptoms may occur hours to days after concomitant use, particularly after dose increases. Serotonin syndrome may occur within recommended dose ranges. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome. 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.
    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).
    Norfloxacin: (Moderate) Use granisetron with caution in combination with norfloxacin due to an increased risk for QT prolongation and torsade de pointes (TdP). Granisetron has been associated with QT prolongation. Quinolones have been associated with QT prolongation and TdP. For norfloxacin specifically, extremely rare cases of TdP were reported during post-marketing surveillance. These reports generally involved patients with concurrent medical conditions or concomitant medications that may have been contributory.
    Octreotide: (Moderate) Use granisetron with caution in combination with octreotide due to increased risk for QT prolongation and torsade de pointes (TdP). Granisetron has been associated with QT prolongation. Arrhythmias, sinus bradycardia, and conduction disturbances have occurred during octreotide therapy warranting more cautious monitoring during octreotide administration in higher risk patients with cardiac disease. Since bradycardia is a risk factor for development of TdP the potential occurrence of bradycardia during octreotide administration could theoretically increase the risk of TdP in patients receiving drugs that prolong the QT interval.
    Ofloxacin: (Moderate) Use granisetron with caution in combination with ofloxacin due to the risk of QT prolongation. Granisetron has been associated with QT prolongation. Quinolones have been associated with a risk of QT prolongation and torsade de pointes (TdP). Although extremely rare, TdP has been reported during postmarketing surveillance of ofloxacin. These reports generally involved patients with concurrent medical conditions or concomitant medications that may have been contributory.
    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.
    Olodaterol: (Moderate) Use granisetron with caution in combination with long-acting beta-agonists due to the risk of QT prolongation. Granisetron has been associated with QT prolongation. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    Ombitasvir; Paritaprevir; 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.
    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.
    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) Serotonin syndrome can occur during concomitant use of opiate agonists with serotonergic drugs, such as serotonin-receptor antagonists. Symptoms may occur hours to days after concomitant use, particularly after dose increases. Serotonin syndrome may occur within recommended dose ranges. Inform patients taking this combination of the possible increased risk and monitor for the emergence of serotonin syndrome. Discontinue all serotonergic agents and initiate symptomatic treatment if serotonin syndrome occurs.
    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: (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 phenelzine. 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.
    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.
    Phenylephrine; Promethazine: (Moderate) Use granisetron with caution in combination with promethazine due to increased risk for QT prolongation and torsade de pointes (TdP). Granisetron has been associated with QT prolongation. Promethazine, a phenothiazine, is associated with a possible risk for QT prolongation.
    Pimavanserin: (Major) Pimavanserin may cause QT prolongation and should generally be avoided in patients receiving other medications known to prolong the QT interval, 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: (Severe) 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.
    Pirbuterol: (Minor) Use granisetron with caution in combination with short-acting beta-agonists due to the risk of QT prolongation. Granisetron has been associated with QT prolongation. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    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.
    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) Use granisetron with caution in combination with promethazine due to increased risk for QT prolongation and torsade de pointes (TdP). Granisetron has been associated with QT prolongation. Promethazine, a phenothiazine, is associated with a possible risk for QT prolongation.
    Propafenone: (Major) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering granisetron with propafenone. Granisetron has been associated with QT prolongation. Propafenone, a Class IC antiarrhythmic, also increases the QT interval, but largely due to prolongation of the QRS interval.
    Quetiapine: (Major) Due to a possible risk for QT prolongation and torsade de pointes (TdP), concurrent use of granisetron and quetiapine should be avoided if possible. 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. Limited data, including some case reports, suggest that quetiapine may be associated with a significant prolongation of the QTc interval in rare instances. According to its manufacturer, use of quetiapine should be avoided in combination with drugs known to increase the QT interval.
    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.
    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.
    Remifentanil: (Moderate) Concurrent use of remifentanil with other drugs that affect the serotonergic neurotransmitter system has resulted in serotonin syndrome. If concurrent use is necessary, closely monitor the patient, particularly during remifentanil initiation and dosage adjustment. Discontinue remifentanil if serotonin syndrome is suspected.
    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.
    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.
    Salmeterol: (Moderate) Use granisetron with caution in combination with long-acting beta-agonists due to the risk of QT prolongation. Granisetron has been associated with QT prolongation. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    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: (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 selegiline. 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.
    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.
    Short-acting beta-agonists: (Minor) Use granisetron with caution in combination with short-acting beta-agonists due to the risk of QT prolongation. Granisetron has been associated with QT prolongation. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    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.
    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) Monitor ECGs for QT prolongation and monitor electrolytes if coadministration of sorafenib with granisetron is necessary; correct any 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) 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 TdP, such as granisetron, should be used cautiously with sotalol. Sotalol administration is associated with QT prolongation and torsades de pointes (TdP). Proarrhythmic events should be anticipated after initiation of therapy and after each upward dosage adjustment.
    Sparfloxacin: (Severe) 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., sparfloxacin) and/or are arrhythmogenic, may result in clinical consequences.
    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) Caution is advised with the concomitant use of tamoxifen and granisetron due to an increased risk of QT prolongation. Granisetron has also been associated with QT prolongation. Tamoxifen has been reported to prolong the QT interval, usually in overdose or when used in high doses. Rare case reports of QT prolongation have also been described when tamoxifen is used at lower doses.
    Telaprevir: (Moderate) Close clinical monitoring is advised when administering granisetron with telaprevir due to an increased potential for granisetron-related adverse events. If granisetron dose adjustments are made, re-adjust the dose upon completion of telaprevir treatment. Although this interaction has not been studied, predictions about the interaction can be made based on the metabolic pathway of granisetron. Granisetron is metabolized by the hepatic isoenzyme CYP3A4; telaprevir inhibits this isoenzyme. Coadministration may result in elevated granisetron plasma concentrations.
    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.
    Telithromycin: (Moderate) Use granisetron with caution in combination with telithromycin due to the risk of QT prolongation. Granisetron has been associated with QT prolongation. Telithromycin is associated with QT prolongation and torsade de pointes (TdP).
    Telotristat Ethyl: (Moderate) Use caution if coadministration of telotristat ethyl and granisetron is necessary, as the systemic exposure of granisetron may be decreased resulting in reduced efficacy. If these drugs are used together, monitor patients for suboptimal efficacy of granisetron; consider increasing the dose of granisetron if necessary. Granisetron is a CYP3A4 substrate. The mean Cmax and AUC of another sensitive CYP3A4 substrate was decreased by 25% and 48%, respectively, when coadministered with telotristat ethyl; the mechanism of this interaction appears to be that telotristat ethyl increases the glucuronidation of the CYP3A4 substrate.
    Terbutaline: (Minor) Use granisetron with caution in combination with short-acting beta-agonists due to the risk of QT prolongation. Granisetron has been associated with QT prolongation. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    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: (Severe) 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.
    Tiotropium; Olodaterol: (Moderate) Use granisetron with caution in combination with long-acting beta-agonists due to the risk of QT prolongation. Granisetron has been associated with QT prolongation. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    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.
    Tranylcypromine: (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 tranylcypromine. 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.
    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.
    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.
    Umeclidinium; Vilanterol: (Moderate) Use granisetron with caution in combination with long-acting beta-agonists due to the risk of QT prolongation. Granisetron has been associated with QT prolongation. Beta-agonists may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses, when associated with hypokalemia, or when used with other drugs known to prolong the QT interval. This risk may be more clinically significant with long-acting beta-agonists as compared to short-acting beta-agonists.
    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) Use granisetron with caution in combination with vardenafil due to the risk of QT prolongation. Granisetron has been associated with QT prolongation. Vardenafil is associated with QT prolongation. Both therapeutic and supratherapeutic doses of vardenafil produce an increase in QTc interval.
    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.
    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.

    PREGNANCY AND LACTATION

    Pregnancy

    There are no available data on the use of granisetron in pregnant women; however, animal studies have revealed no teratogenic effects. Granisetron injection, patch, and oral formulations are classified as FDA pregnancy risk category B. It is not known if granisetron crosses the placenta; however, due to its low molecular weight, passage across the placental barrier is expected. Some formulations of granisetron injection contain benzyl alcohol which may cross the placenta and could result in untoward adverse events in the newly born neonate. Granisetron should be used during pregnancy only if the benefit to the mother outweighs the potential risk to the fetus. Other alternatives exist. When necessary, the American College of Obstetricians and Gynecologists recommends the use of ondansetron for the treatment of nausea and vomiting of pregnancy in patients who are dehydrated, requiring IV fluid replacement, and have failed other therapies.

    According to the manufacturer, 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. If a breast-feeding infant experiences an adverse effect related to a maternally administered drug, healthcare providers are encouraged to report the adverse effect to the FDA.

    MECHANISM OF ACTION

    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.

    PHARMACOKINETICS

    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).