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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)†.
    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.

    †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:
    - Protect from light
    - Store at controlled room temperature (between 68 and 77 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 (unspecified) / 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; Oxycodone: (Major) 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. If concomitant treatment is clinically warranted, careful observation of the patient is advised, especially during initiation of the second therapy and after dosage increases of either agent. Instruct patients to immediately report symptoms of agitation, hallucinations, tachycardia, fever, excessive sweating, shivering or shaking, muscle twitching or stiffness, trouble with coordination, nausea, vomiting, or diarrhea.
    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.
    Albuterol: (Minor) 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 the beta-agonists. Beta-agonists, such as albuterol, may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Albuterol; Ipratropium: (Minor) 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 the beta-agonists. Beta-agonists, such as albuterol, may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Alfuzosin: (Major) Due to a possible risk for QT prolongation and torsade de pointes (TdP), granisetron and alfuzosin 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. Based on electrophysiology studies performed by its manufacturer, alfuzosin has a slight effect to prolong the QT interval. The QT prolongation appeared less with alfuzosin 10 mg than with 40 mg. The manufacturer warns that the QT effect of alfuzosin should be considered prior to administering the drug to patients taking other medications known to prolong the QT interval.
    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.
    Anthracyclines: (Major) According to the manufacturer, caution is advised if granisetron is administered to patients receiving drugs known to cause QT prolongation, including cardio-toxic chemotherapy. Cumulative high-dose anthracyclines may aggravate cardiac arrhythmias, including QT prolongation, that are possible with granisetron. Acute ECG changes during anthracycline therapy are usually transient and include ST-T wave changes, QT prolongation, and changes in QRS voltage. Sinus tachycardia is the most common arrhythmia, but other arrhythmias such as supraventricular tachycardia (SVT), ventricular tachycardia, heart block, and premature ventricular contractions (PVCs) have been reported during anthracycline therapy.
    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) 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 the beta-agonists. Beta-agonists, such as albuterol, may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Aripiprazole: (Major) QT prolongation has occurred during therapeutic use of aripiprazole and following overdose. 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. Granisetron should be used cautiously and with close monitoring with aripiprazole
    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; Oxycodone: (Major) 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. If concomitant treatment is clinically warranted, careful observation of the patient is advised, especially during initiation of the second therapy and after dosage increases of either agent. Instruct patients to immediately report symptoms of agitation, hallucinations, tachycardia, fever, excessive sweating, shivering or shaking, muscle twitching or stiffness, trouble with coordination, nausea, vomiting, or diarrhea.
    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: (Major) QT prolongation has occurred during therapeutic use of atomoxetine and following overdose. Atomoxetine is considered a drug with a possible risk of torsade de pointes (TdP). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with atomoxetine include granisetron.
    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: (Major) Due to an increased risk for QT prolongation and torsade de pointes (TdP), caution is advised when administering granisetron with azithromycin. Granisetron has been associated with QT prolongation, and cases of QT prolongation and TdP have been reported with the post-marketing use of azithromycin. 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.
    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.
    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: (Major) Potential QT prolongation has been reported in limited case reports with metronidazole. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with metronidazole include granisetron.
    Bismuth Subsalicylate; Metronidazole; Tetracycline: (Major) Potential QT prolongation has been reported in limited case reports with metronidazole. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with metronidazole include granisetron.
    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.
    Brigatinib: (Moderate) Monitor for decreased efficacy of granisetron if coadministration with brigatinib is necessary. Granisetron is a CYP3A substrate and brigatinib induces CYP3A in vitro; plasma concentrations of granisetron may decrease.
    Budesonide; Formoterol: (Moderate) 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 the beta-agonists. Beta-agonists, such as albuterol, may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    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.
    Ceritinib: (Major) Periodically monitor electrolytes and ECGs in patients receiving concomitant treatment with ceritinib and granisetron; 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.
    Chloroprocaine: (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., local anesthetics) and/or are arrhythmogenic, may result in clinical consequences.
    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.
    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: (Major) Due to an increased risk for QT prolongation and torsade de pointes (TdP), caution is advised when administering granisetron with ciprofloxacin. Granisetron has been associated with QT prolongation. According to the manufacturer, use of granisetron in patients concurrently treated with other potentially QT prolonging drugs, such as ciprofloxacin, may result in clinical consequences.
    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.
    Clozapine: (Major) Due to a possible risk for QT prolongation and torsade de pointes (TdP), granisetron and clozapine 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. Treatment with clozapine has been associated with QT prolongation, TdP, cardiac arrest, and sudden death. The manufacturer of clozapine recommends caution during concurrent use with medications known to cause 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.
    Cobicistat; Elvitegravir; 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.
    Cobicistat; Elvitegravir; 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.
    Codeine; Phenylephrine; Promethazine: (Major) Promethazine carries a possible risk of QT prolongation. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with promethazine include granisetron.
    Codeine; Promethazine: (Major) Promethazine carries a possible risk of QT prolongation. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with promethazine include granisetron.
    Crizotinib: (Major) Monitor ECGs for QT prolongation and monitor electrolytes in patients receiving crizotinib concomitantly with granisetron. An interruption of therapy, dose reduction, or discontinuation of therapy may be necessary for crizotinib patients if QT prolongation occurs. Crizotinib has been associated with concentration-dependent QT prolongation; granisetron has also been associated with QT prolongation.
    Cyclobenzaprine: (Major) Both cyclobenzaprine and granisetron are associated with a possible risk for QT prolongation and torsade de pointes (TdP); therefore, caution and close monitoring are recommended during co-administration of cyclobenzaprine and granisetron. In addition, 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.
    Dasabuvir; Ombitasvir; Paritaprevir; Ritonavir: (Major) The use of ritonavir could result in QT prolongation. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with ritonavir include granisetron. In addition, concurrent administration may result in elevated granisetron plasma concentrations. Granisetron is metabolized by the hepatic isoenzyme CYP3A4; ritonavir is an inhibitor of this enzyme.
    Dasatinib: (Major) Due to a possible risk for QT prolongation and torsade de pointes (TdP), granisetron and dasatinib 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. In vitro studies have shown that dasatinib has the potential to prolong cardiac ventricular repolarization (prolong QT interval). In addition, dasatinib is a weak inhibitor of CYP3A4. Coadministration of dasatinib with granisetron, a CYP3A4 substrate, may result in an elevated plasma concentration of granisetron.
    Degarelix: (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 with granisetron include degarelix.
    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: (Major) 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. Clinically relevant QTc prolongation may occur with deutetrabenazine. Granisetron has been associated with QT prolongation.
    Dextromethorphan; Promethazine: (Major) Promethazine carries a possible risk of QT prolongation. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with promethazine include granisetron.
    Dextromethorphan; Quinidine: (Major) Granisetron should be used cautiously and with close monitoring with Class IA antiarrhythmics (disopyramide, procainamide, and quinidine). Class IA antiarrhythmics are associated with QT prolongation and torsades de pointes (TdP). Granisetron has been associated with QT prolongation. According to the manufacturer, use of granisetron in patients concurrently treated with drugs known to prolong the QT interval and/or are arrhythmogenic, may result in clinical consequences.
    Disopyramide: (Major) Granisetron should be used cautiously and with close monitoring with Class IA antiarrhythmics (disopyramide, procainamide, and quinidine). Class IA antiarrhythmics are associated with QT prolongation and torsades de pointes (TdP). Granisetron has been associated with QT prolongation. According to the manufacturer, use of granisetron in patients concurrently treated with drugs known to prolong the QT interval and/or are arrhythmogenic, may result in clinical consequences.
    Dofetilide: (Severe) Because of the potential for torsades de pointes (TdP), concurrent use of granisetron and dofetilide is contraindicated. Dofetilide, a Class III antiarrhythmic agent, is associated with a well-established risk of QT prolongation and 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.
    Dolasetron: (Major) Because of the potential risk and severity of serotonin syndrome, use caution and monitor closely when administering dolasetron 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, dolasetron has been associated with a dose-dependent prolongation in the QT, PR, and QRS intervals on an electrocardiogram. Granisetron has a possible risk for QT prolongation and torsade de pointes (TdP) and should be used cautiously and with close monitoring with dolasetron.
    Donepezil: (Major) Case reports indicate that QT prolongation and torsade de pointes (TdP) can occur during donepezil therapy. Donepezil is considered a drug with a known risk of TdP. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with donepezil include granisetron.
    Donepezil; Memantine: (Major) Case reports indicate that QT prolongation and torsade de pointes (TdP) can occur during donepezil therapy. Donepezil is considered a drug with a known risk of TdP. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with donepezil include granisetron.
    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: (Major) Although data are limited, coadministration of efavirenz and granisetron may increase the risk for QT prolongation and torsade de pointes (TdP). QT prolongation has been observed with use of efavirenz. Granisetron has also been associated with QT prolongation. In addition, efavirenz may induce the CYP3A4 metabolism of granisetron; potentially reducing the efficacy of granisetron by decreasing its systemic exposure.
    Efavirenz; Emtricitabine; Tenofovir: (Major) Although data are limited, coadministration of efavirenz and granisetron may increase the risk for QT prolongation and torsade de pointes (TdP). QT prolongation has been observed with use of efavirenz. Granisetron has also been associated with QT prolongation. In addition, efavirenz may induce the CYP3A4 metabolism of granisetron; potentially reducing the efficacy of granisetron by decreasing its systemic exposure.
    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: (Major) Eliglustat is predicted to cause PR, QRS, and/or QT prolongation at significantly elevated plasma concentrations. Drugs with a possible risk for QT prolongation and torsade de pointes (TdP) that should be used cautiously and with close monitoring with eliglustat include granisetron.
    Emtricitabine; Rilpivirine; Tenofovir alafenamide: (Major) Due to a possible risk for QT prolongation and torsade de pointes (TdP), granisetron and rilpivirine 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. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation.
    Emtricitabine; Rilpivirine; Tenofovir disoproxil fumarate: (Major) Due to a possible risk for QT prolongation and torsade de pointes (TdP), granisetron and rilpivirine 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. 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.
    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: (Major) Escitalopram has been associated with QT prolongation. Coadministration with other drugs that have a possible risk for QT prolongation and torsade de pointes (TdP), such as granisetron, should be done with caution and close monitoring.
    Ester local anesthetics: (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., local anesthetics) and/or are arrhythmogenic, may result in clinical consequences.
    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: (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 with granisetron include ezogabine.
    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: (Major) Fingolimod initiation results in decreased heart rate and may prolong the QT interval. After the first fingolimod dose, overnight monitoring with continuous ECG in a medical facility is advised for patients taking QT prolonging drugs with a known risk of torsades de pointes (TdP). 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. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with fingolimod include granisetron.
    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: (Severe) The concomitant administration of fluconazole and granisetron is contraindicated. Fluconazole has been associated with QT prolongation and is contraindicated for use with other drugs that both prolong the QT interval and are CYP3A4 substrates, such as granisetron. Coadministration may result in elevated granisetron plasma concentrations, causing an increased risk for adverse events, such as QT prolongation.
    Fluoxetine: (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 fluoxetine. 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, because QT prolongation and torsade de pointes (TdP) have been reported in patients treated with fluoxetine, the manufacturer recommends caution when using fluoxetine with other drugs that prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP include granisetron.
    Fluoxetine; Olanzapine: (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 fluoxetine. 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, because QT prolongation and torsade de pointes (TdP) have been reported in patients treated with fluoxetine, the manufacturer recommends caution when using fluoxetine with other drugs that prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP include granisetron. (Major) Due to a possible risk for QT prolongation and torsade de pointes (TdP), granisetron and olanzapine 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. 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) Due to a possible risk for QT prolongation and torsade de pointes (TdP), granisetron and fluphenazine should be used together cautiously. 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. Fluphenazine, a phenothiazine, is associated with a possible risk for QT prolongation.
    Fluticasone; Salmeterol: (Moderate) 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 the beta-agonists. Beta-agonists, such as albuterol, may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Fluticasone; Umeclidinium; Vilanterol: (Moderate) 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 the beta-agonists. Beta-agonists, such as albuterol, may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Fluticasone; Vilanterol: (Moderate) 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 the beta-agonists. Beta-agonists, such as albuterol, may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Fluvoxamine: (Major) Concomitant use of fluvoxamine and granisetron may increase the risk of serotonin syndrome, QT prolongation, and torsade de pointes. Cases of QT prolongation and TdP have been reported during postmarketing use of fluvoxamine. Granisetron has been associated with QT prolongation. In addition, both fluvoxamine and granisetron have central serotonin-enhancing effects; therefore, 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, all serotonergic agents should be discontinued and appropriate medical treatment should be implemented.
    Formoterol: (Moderate) 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 the beta-agonists. Beta-agonists, such as albuterol, may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Formoterol; Mometasone: (Moderate) 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 the beta-agonists. Beta-agonists, such as albuterol, may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    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: (Major) Due to an increased risk for QT prolongation and torsade de pointes (TdP), caution is advised when administering granisetron with gemifloxacin. Granisetron has been associated with QT prolongation. According to the manufacturer, use of granisetron in patients concurrently treated with other drugs known to prolong the QT interval and/or are arrhythmogenic, may result in clinical consequences. 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: (Major) 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. Although QT interval prolongation has not been reported with gemtuzumab, it has been reported with other drugs that contain calicheamicin. Granisetron has been associated with QT prolongation.
    Glycopyrrolate; Formoterol: (Moderate) 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 the beta-agonists. Beta-agonists, such as albuterol, may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Goserelin: (Major) Granisetron should be used cautiously and with close monitoring with goserelin. 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. Androgen deprivation therapy (e.g., goserelin) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval.
    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: (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., haloperidol) and/or are arrhythmogenic, may result in clinical consequences.
    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.
    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: (Major) Post-marketing data indicate that hydroxyzine causes QT prolongation and Torsade de Pointes (TdP). Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with hydroxyzine include granisetron.
    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: (Major) 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. If concomitant treatment is clinically warranted, careful observation of the patient is advised, especially during initiation of the second therapy and after dosage increases of either agent. Instruct patients to immediately report symptoms of agitation, hallucinations, tachycardia, fever, excessive sweating, shivering or shaking, muscle twitching or stiffness, trouble with coordination, nausea, vomiting, or diarrhea.
    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) 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 the beta-agonists. Beta-agonists, such as albuterol, may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Indacaterol; Glycopyrrolate: (Moderate) 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 the beta-agonists. Beta-agonists, such as albuterol, may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    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: (Major) Caution is advised when administering itraconazole with drugs that are known to prolong that QT interval and are metabolized by CYP3A4, such as granisetron. Both granisetron and itraconazole are associated with QT prolongation; coadministration may increase this risk. In addition, coadministration of itraconazole (a potent CYP3A4 inhibitor) with granisetron (a CYP3A4 substrate) may result in elevated granisetron plasma concentrations and an increased risk for adverse events, including QT prolongation. If itraconazole therapy is stopped, it may be prudent to continue close monitoring for up to 2 weeks after discontinuing itraconazole. Once discontinued, the plasma concentration of itraconazole decreases to almost undetectable concentrations within 7 to 14 days. The decline in plasma concentrations may be even more gradual in patients with hepatic cirrhosis or who are receiving concurrent CYP3A4 inhibitors.
    Ivacaftor: (Moderate) Use caution when administering ivacaftor and granisetron concurrently. Ivacaftor is an inhibitor of CYP3A. Co-administration of ivacaftor with CYP3A substrates, such as granisetron, can increase granisetron exposure leading to increased or prolonged therapeutic effects and adverse events.
    Ketoconazole: (Major) Caution is advised when administering ketoconazole with drugs that are known to prolong that QT interval and are metabolized by CYP3A4, such as granisetron. Both granisetron and ketoconazole are associated with QT prolongation; coadministration may increase this risk. In addition, coadministration of ketoconazole (a potent CYP3A4 inhibitor) with granisetron (a CYP3A4 substrate) may result in elevated granisetron plasma concentrations and an increased risk for adverse events, including QT prolongation.
    Lapatinib: (Major) Due to a possible risk for QT prolongation and torsade de pointes (TdP), granisetron and lapatinib 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. In vitro, lapatinib, at clinically relevant concentrations, inhibits CYP3A4 and CYP2C8. If lapatinib will be coadministered with granisetron, a CYP3A4 substrate, exercise caution and consider granisetron dose reduction.
    Lenvatinib: (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 lenvatinib. QT prolongation was reported in patients with radioactive iodine-refractory differentiated thyroid cancer (RAI-refractory DTC) in a double-blind, randomized, placebo-controlled clinical trial after receiving lenvatinib daily at the recommended dose; the QT/QTc interval was not prolonged, however, after a single 32 mg dose (1.3 times the recommended daily dose) in healthy subjects.
    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.
    Leuprolide: (Major) Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with leuprolide include granisetron.
    Leuprolide; Norethindrone: (Major) Androgen deprivation therapy (e.g., leuprolide) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with leuprolide include granisetron.
    Levalbuterol: (Minor) 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 the beta-agonists. Beta-agonists, such as albuterol, may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Levofloxacin: (Major) Concurrent use of granisetron and levofloxacin should be avoided due to an increased risk for QT prolongation and torsade de pointes (TdP). Levofloxacin has been associated with prolongation of the QT interval and infrequent cases of arrhythmia. Additionally, rare cases of TdP have been spontaneously reported during postmarketing surveillance in patients receiving levofloxacin. Granisetron has also 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., levofloxacin) and/or are arrhythmogenic, may result in clinical consequences.
    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: (Major) Granisetron and lithium are associated with QT prolongation. Coadministration may increase the risk of QT prolongation; therefore, granisetron and lithium should be coadministered with caution and close monitoring. Because of the potential risk and severity of serotonin syndrome, use caution when administering granisetron with other drugs that have serotonergic properties such as lithium. 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.
    Long-acting beta-agonists: (Moderate) 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 the beta-agonists. Beta-agonists, such as albuterol, may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    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: (Major) At high doses, loperamide has been associated with serious cardiac toxicities, including syncope, ventricular tachycardia, QT prolongation, torsade de pointes (TdP), and cardiac arrest. Drugs with a possible risk for QT prolongation and TdP, like granisetron, should be used cautiously and with close monitoring with loperamide.
    Loperamide; Simethicone: (Major) At high doses, loperamide has been associated with serious cardiac toxicities, including syncope, ventricular tachycardia, QT prolongation, torsade de pointes (TdP), and cardiac arrest. Drugs with a possible risk for QT prolongation and TdP, like granisetron, should be used cautiously and with close monitoring with loperamide.
    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. (Major) The use of ritonavir could result in QT prolongation. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with ritonavir include granisetron. In addition, concurrent administration may result in elevated granisetron plasma concentrations. Granisetron is metabolized by the hepatic isoenzyme CYP3A4; ritonavir is an inhibitor of this enzyme.
    Lumacaftor; Ivacaftor: (Moderate) Use caution when administering ivacaftor and granisetron concurrently. Ivacaftor is an inhibitor of CYP3A. Co-administration of ivacaftor with CYP3A substrates, such as granisetron, can increase granisetron exposure leading to increased or prolonged therapeutic effects and adverse events.
    Maprotiline: (Major) Due to a possible risk for QT prolongation and torsade de pointes (TdP), granisetron and maprotiline 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. 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: (Major) Due to a possible risk for QT prolongation and torsade de pointes (TdP), granisetron and mefloquine 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. 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: (Major) Promethazine carries a possible risk of QT prolongation. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with promethazine include granisetron.
    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) 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 the beta-agonists. Beta-agonists, such as albuterol, may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    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: (Major) Potential QT prolongation has been reported in limited case reports with metronidazole. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with metronidazole include granisetron.
    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, RU-486: (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: (Major) Concomitant use of mirtazapine and granisetron may increase the risk of serotonin syndrome, QT prolongation, and torsade de pointes. Cases of QT prolongation, TdP, ventricular tachycardia, and sudden death have been reported during use of mirtazapine, primarily after overdose or in patients with risk factors for QT prolongation (e.g., concurrent use of other medications associated with QT prolongation). Granisetron has been associated with QT prolongation. In addition, both mirtazapine and granisetron have central serotonin-enhancing effects; therefore, 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, all serotonergic agents should be discontinued and appropriate medical treatment should be implemented.
    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: (Major) Because of the potential risk and severity of serotonin syndrome, caution and careful monitoring are recommended when coadministering drugs that have serotonergic properties such as morphine and serotonin-receptor antagonists. 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. Morphine and the serotonin-receptor antagonist should be discontinued if serotonin syndrome occurs and supportive symptomatic treatment should be initiated.
    Morphine; Naltrexone: (Major) Because of the potential risk and severity of serotonin syndrome, caution and careful monitoring are recommended when coadministering drugs that have serotonergic properties such as morphine and serotonin-receptor antagonists. 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. Morphine and the serotonin-receptor antagonist should be discontinued if serotonin syndrome occurs and supportive symptomatic treatment should be initiated.
    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: (Major) Due to an increased risk for QT prolongation and torsade de pointes (TdP), caution is advised when administering granisetron with norfloxacin. Granisetron has been associated with QT prolongation. According to the manufacturer, use of granisetron in patients concurrently treated with other drugs known to prolong the QT interval and/or are arrhythmogenic, may result in clinical consequences. 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: (Major) Due to a possible risk for QT prolongation and torsade de pointes (TdP), granisetron and octreotide 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. 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: (Major) Due to an increased risk for QT prolongation and torsade de pointes (TdP), caution is advised when administering granisetron with ofloxacin. Granisetron has been associated with QT prolongation. Some quinolones, including ofloxacin, have also been associated with QT prolongation. Additionally, post-marketing surveillance for ofloxacin has identified very rare cases of TdP.
    Olanzapine: (Major) Due to a possible risk for QT prolongation and torsade de pointes (TdP), granisetron and olanzapine 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. 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) 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 the beta-agonists. Beta-agonists, such as albuterol, may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Ombitasvir; Paritaprevir; Ritonavir: (Major) The use of ritonavir could result in QT prolongation. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with ritonavir include granisetron. In addition, concurrent administration may result in elevated granisetron plasma concentrations. Granisetron is metabolized by the hepatic isoenzyme CYP3A4; ritonavir is an inhibitor of this enzyme.
    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) Monitor electrolytes and ECGs for QT prolongation if coadministration of granisetron with osimertinib is necessary; an interruption of osimertinib therapy and dose reduction may be necessary if QT prolongation occurs. Concentration-dependent QTc prolongation occurred during clinical trials of osimertinib, and 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: (Major) 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. If concomitant treatment is clinically warranted, careful observation of the patient is advised, especially during initiation of the second therapy and after dosage increases of either agent. Instruct patients to immediately report symptoms of agitation, hallucinations, tachycardia, fever, excessive sweating, shivering or shaking, muscle twitching or stiffness, trouble with coordination, nausea, vomiting, or diarrhea.
    Paliperidone: (Major) Paliperidone has been associated with QT prolongation; however, torsade de pointes (TdP) has not been reported. 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 considered necessary by the practitioner, and the patient has known risk factors for cardiac disease or arrhythmia, then 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: (Major) Cautious use of pasireotide and drugs that prolong the QT interval is needed, as coadministration may have additive effects on the prolongation of 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.
    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) Due to a possible risk for QT prolongation and torsade de pointes (TdP), granisetron and perphenazine should be used together cautiously. 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. Perphenazine, a phenothiazine, is associated with a possible risk for QT prolongation.
    Perphenazine; Amitriptyline: (Minor) Due to a possible risk for QT prolongation and torsade de pointes (TdP), granisetron and perphenazine should be used together cautiously. 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. 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: (Major) Promethazine carries a possible risk of QT prolongation. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with promethazine include granisetron.
    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) 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 the beta-agonists. Beta-agonists, such as albuterol, may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Posaconazole: (Severe) The concurrent use of posaconazole and granisetron is contraindicated due to the risk of life threatening arrhythmias such as torsades de pointes (TdP). Posaconazole is a potent inhibitor of CYP3A4, an isoenzyme responsible for the metabolism of granisetron. These drugs used in combination may result in elevated granisetron plasma concentrations, causing an increased risk for granisetron-related adverse events, such as QT prolongation. Additionally, posaconazole has been associated with prolongation of the QT interval as well as rare cases of TdP; avoid use with other drugs that may prolong the QT interval and are metabolized through CYP3A4, such as granisetron.
    Primaquine: (Major) Due to the potential for QT interval prolongation with primaquine, caution is advised with other drugs that prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with primaquine include granisetron.
    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.
    Procaine: (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., local anesthetics) and/or are arrhythmogenic, may result in clinical consequences.
    Prochlorperazine: (Minor) Due to a possible risk for QT prolongation and torsade de pointes (TdP), granisetron and prochlorperazine should be used together cautiously. 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. Phenothiazines have been reported to prolong the QT interval. If coadministration is considered necessary, and the patient has known risk factors for cardiac disease or arrhythmia, then close monitoring is essential.
    Promethazine: (Major) Promethazine carries a possible risk of QT prolongation. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with promethazine include granisetron.
    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: (Major) Ranolazine is associated with dose- and plasma concentration-related increases in the QTc interval. The mean increase in QTc is about 6 milliseconds, measured at the tmax of the maximum dosage (1000 mg PO twice daily). However, in 5% of the population studied, increases in the QTc of at least 15 milliseconds have been reported. 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. In addition, in vitro studies indicate that ranolazine and its metabolite are inhibitors of CYP3A isoenzymes. The impact of coadministering ranolazine with other CYP3A4 substrates has not been studied. Ranolazine may theoretically increase plasma concentrations of CYP3A4 substrates, potentially leading to adverse reactions, such as QT prolongation. Drugs that are CYP3A4 substrates that also have a possible risk for QT prolongation and TdP that should be used cautiously with ranolazine include granisetron.
    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.
    Regadenoson: (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 with granisetron include regadenoson.
    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. Systemic exposure of granisetron may also be increased resulting in increase in treatment-related adverse reactions. 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 is also a moderate CYP3A4 inhibitor and granisetron is a CYP3A4 substrate.
    Ribociclib; Letrozole: (Major) Avoid coadministration of ribociclib with granisetron due to an increased risk for QT prolongation. Systemic exposure of granisetron may also be increased resulting in increase in treatment-related adverse reactions. 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 is also a moderate CYP3A4 inhibitor and granisetron is a CYP3A4 substrate.
    Rilpivirine: (Major) Due to a possible risk for QT prolongation and torsade de pointes (TdP), granisetron and rilpivirine 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. Supratherapeutic doses of rilpivirine (75 to 300 mg/day) have caused QT prolongation.
    Risperidone: (Major) Risperidone has been associated with a possible risk for QT prolongation and/or torsade de pointes; however, data are currently lacking to establish causality in association with torsades de pointes (TdP). Reports of QT prolongation and torsades de pointes during risperidone therapy are noted by the manufacturer, primarily in the overdosage setting. Since risperidone may prolong the QT interval, it should be used cautiously with other agents also known to have this effect, taking into account the patient's underlying disease state(s) and additional potential risk factors. If coadministration is chosen, and the patient has known risk factors for cardiac disease or arrhythmia, then the patient should be closely monitored clinically. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously with risperidone include granisetron.
    Ritonavir: (Major) The use of ritonavir could result in QT prolongation. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with ritonavir include granisetron. In addition, concurrent administration may result in elevated granisetron plasma concentrations. Granisetron is metabolized by the hepatic isoenzyme CYP3A4; ritonavir is an inhibitor of this enzyme.
    Romidepsin: (Major) Due to a possible risk for QT prolongation and torsade de pointes (TdP), granisetron and romidepsin 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. Romidepsin has been reported to prolong the QT interval. If romidepsin must be coadministered with another drug that prolongs the QT interval, appropriate cardiovascular monitoring precautions should be considered, such as the monitoring of electrolytes and ECGs at baseline and periodically during treatment.
    Salmeterol: (Moderate) 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 the beta-agonists. Beta-agonists, such as albuterol, may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    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) There have been post-marketing reports of QT prolongation and Torsade de Pointes (TdP) during treatment with sertraline; therefore, caution is advisable when using sertraline in patients with risk factors for QT prolongation, including concurrent use of other drugs that prolong the QTc interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with sertraline include granisetron. In addition, because of the potential risk and severity of serotonin syndrome, use caution when administering granisetron with other drugs that have serotonergic properties such as sertraline. 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.
    Short-acting beta-agonists: (Minor) 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 the beta-agonists. Beta-agonists, such as albuterol, may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Solifenacin: (Major) Granisetron should be used cautiously and with close monitoring with solifenacin. Solifenacin has been associated with dose-dependent prolongation of the QT interval. Torsades de pointes (TdP) has been reported with post-marketing use, although causality was not determined. 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.
    Sorafenib: (Major) Due to a possible risk for QT prolongation and torsade de pointes (TdP), granisetron and sorafenib 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. Sorafenib has been associated with QT prolongation. If sorafenib and another drug that prolongs the QT interval must be coadministered, ECG monitoring is recommended; closely monitor the patient for QT interval 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.
    Sulfamethoxazole; Trimethoprim, SMX-TMP, Cotrimoxazole: (Major) QT prolongation resulting in ventricular tachycardia and torsade de pointes (TdP) have been reported during post-marketing use of sulfamethoxazole; trimethoprim. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with sulfamethoxazole; trimethoprim include granisetron.
    Sunitinib: (Major) Due to a possible risk for QT prolongation and torsade de pointes (TdP), granisetron and sunitinib 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. Sunitinib can prolong the QT interval.
    Tacrolimus: (Major) Due to a possible risk for QT prolongation and torsade de pointes (TdP), granisetron and tacrolimus 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. Tacrolimus causes QT prolongation. Reducing the tacrolimus dose, close monitoring of tacrolimus whole blood concentrations, and monitoring for QT prolongation is recommended when administrating tacrolimus with other substrates and/or inhibitors of CYP3A4 that also have the potential to prolong the QT interval such as granisetron.
    Tamoxifen: (Major) Caution is advised with the concomitant use of tamoxifen and granisetron due to an increased risk of 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. Granisetron has also been associated with QT prolongation.
    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: (Major) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering telavancin with granisetron. Both granisetron and telavancin have been associated with QT prolongation.
    Telithromycin: (Major) Due to a possible risk for QT prolongation and torsade de pointes (TdP), granisetron and telithromycin 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. In addition, telithromycin is an inhibitor of and granisetron is a substrate of the CYP3A4 isoenzyme; therefore, coadministration may lead to increased concentrations of granisetron.
    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) 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 the beta-agonists. Beta-agonists, such as albuterol, may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    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.
    Tetracaine: (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., local anesthetics) and/or are arrhythmogenic, may result in clinical consequences.
    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) 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 the beta-agonists. Beta-agonists, such as albuterol, may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Tizanidine: (Major) Granisetron should be used cautiously and with close monitoring with tizanidine. Tizanidine administration may result in QT prolongation. 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.
    Tolterodine: (Major) Due to the potential for QT prolongation and torsade de pointes (TdP), caution is advised when administering granisetron with tolterodine. 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) Toremifene has been shown to prolong the QTc interval in a dose- and concentration-related manner. Drugs with a possible risk for QT prolongation and torsade de pointes (TdP) that should be used cautiously with toremifene include granisetron.
    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) Avoid coadministration of granisetron and trazodone. 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. Trazodone can prolong the QT/QTc interval at therapeutic doses. There are post-marketing reports of torsade de pointes (TdP). Therefore, the manufacturer recommends avoiding trazodone in patients receiving other drugs that increase the QT interval. In addition, because of the potential risk and severity of serotonin syndrome, use caution when administering granisetron with other drugs that have serotonergic properties such as trazodone. 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.
    Tricyclic antidepressants: (Minor) Both tricyclic antidepressants (TCAs) and granisetron are associated with a possible risk for QT prolongation and torsade de pointes (TdP); therefore, caution and close monitoring are recommended during co-administration of TCAs and granisetron. In addition, because of the potential risk and severity of serotonin syndrome, use caution when administering granisetron with other drugs that have serotonergic properties such as tricyclic antidepressants. 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.
    Trifluoperazine: (Minor) Due to a possible risk for QT prolongation and torsade de pointes (TdP), granisetron and trifluoperazine should be used together cautiously. 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. Trifluoperazine, a phenothiazine, is associated with a possible risk for QT prolongation.
    Triptorelin: (Major) Androgen deprivation therapy (e.g., triptorelin) prolongs the QT interval; the risk may be increased with the concurrent use of drugs that may prolong the QT interval. Drugs with a possible risk for QT prolongation and TdP that should be used cautiously and with close monitoring with triptorelin include granisetron.
    Umeclidinium; Vilanterol: (Moderate) 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 the beta-agonists. Beta-agonists, such as albuterol, may be associated with adverse cardiovascular effects including QT interval prolongation, usually at higher doses and/or when associated with hypokalemia.
    Vandetanib: (Major) The manufacturer of vandetanib recommends avoiding coadministration with other drugs that prolong the QT interval due to an increased risk of QT prolongation and torsade de pointes (TdP). Vandetanib can prolong the QT interval in a concentration-dependent manner. TdP and sudden death have been reported in patients receiving vandetanib; granisetron has been associated with QT prolongation. If coadministration is necessary, an ECG is needed, as well as more frequent monitoring of the QT interval. If QTcF is greater than 500 msec, interrupt vandetanib dosing until the QTcF is less than 450 msec; then, vandetanib may be resumed at a reduced dose.
    Vardenafil: (Major) Due to a possible risk for QT prolongation and torsade de pointes (TdP), granisetron and vardenafil should be used together cautiously. 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 (e.g., 4 to 6 msec calculated by individual QT correction).
    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) 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 venlafaxine. 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.
    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: (Major) Caution is advised when administering voriconazole with drugs that are known to prolong that QT interval and are metabolized by CYP3A4, such as granisetron. Both drugs have been associated with QT prolongation; coadministration may increase this risk. Voriconazole has also been associated with rare cases of torsades de pointes, cardiac arrest, and sudden death. In addition, coadministration of voriconazole (a CYP3A4 inhibitor) with granisetron (a CYP3A4 substrate) may result in elevated granisetron plasma concentrations and could increase the risk for adverse events, including QT prolongation. If these drugs are given together, closely monitor for prolongation of the QT interval. Rigorous attempts to correct any electrolyte abnormalities (i.e., potassium, magnesium, calcium) should be made before initiating concurrent therapy.
    Vorinostat: (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. Vorinostat therapy is associated with a risk of QT prolongation and should be used cautiously with granisetron.
    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: (Severe) According to the manufacturer, ziprasidone is contraindicated with any drugs that list QT prolongation as a pharmacodynamic effect when this effect has been described within the contraindications or bolded or boxed warnings of the official labeling for such drugs. Ziprasidone has been associated with a possible risk for QT prolongation and/or torsades de pointes (TdP). Clinical trial data indicate that ziprasidone causes QT prolongation. In one study, ziprasidone increased the QT interval 10 msec more than placebo at the maximum recommended dosage. Comparative data with other antipsychotics have shown that the mean QTc interval prolongation occurring with ziprasidone exceeds that of haloperidol, quetiapine, olanzapine, and risperidone, but is less than that which occurs with thioridazine. Given the potential for QT prolongation, ziprasidone is contraindicated for use with drugs that are known to cause QT prolongation with potential for torsades de pointes including granisetron.

    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).