Granisetron

Granisetron may cause side effects. Tell your doctor if any of these symptoms are severe or do not go away:

• headache
• stomach pain
• heartburn
• constipation
• difficulty falling asleep or staying asleep

Some side effects can be serious. If you experience any of the following symptoms, call your doctor immediately or seek emergency medical treatment:

• hives
• rash
• itching
• difficulty breathing or swallowing
• shortness of breath
• dizziness, light-headedness, or fainting
• fast, slow or irregular heartbeat
• agitation
• hallucinations (seeing things or hearing voices that do not exist)
• fever
• flushing
• excessive sweating
• confusion
• nausea, vomiting, or diarrhea
• loss of coordination
• stiff or twitching muscles
• seizures
• coma (loss of consciousness)

Granisetron may cause other side effects. Call your doctor if you have any unusual problems while taking this medication.

If you experience a serious side effect, you or your doctor may send a report to the Food and Drug Administration's (FDA) MedWatch Adverse Event Reporting program online (http://www.fda.gov/Safety/MedWatch) or by phone (1-800-332-1088).

Granisetron blocks the actions of chemicals in the body that can trigger nausea and vomiting.

Granisetron is used to prevent nausea and vomiting that may be caused by medicine to treat cancer (chemotherapy or radiation).

Granisetron may also be used for purposes not listed in this medication guide.

Granisetron blocks the actions of chemicals in the body that may cause nausea and vomiting.

Granisetron transdermal (skin patch) is used to prevent nausea and vomiting caused by cancer chemotherapy.

Granisetron transdermal may also be used for purposes not listed in this medication guide.

Follow all directions on your medicine label and package. Tell each of your healthcare providers about all your medical conditions, allergies, and all medicines you use.

Follow all directions on your medicine label and package. Tell each of your healthcare providers about all your medical conditions, allergies, and all medicines you use.

You should not take granisetron if you are allergic to it.

To make sure granisetron is safe for you, tell your doctor if you have:

• heart disease;
• a heart rhythm disorder;
• a personal or family history of Long QT syndrome;
• an electrolyte imbalance (such as low levels of potassium or magnesium in your blood); or
• if you have recently had stomach or intestinal surgery.

FDA pregnancy category B. Granisetron is not expected to harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant during treatment.

It is not known whether granisetron passes into breast milk or if it could harm a nursing baby. Tell your doctor if you are breast-feeding a baby.

You should not use granisetron if you are allergic to it.

To make sure granisetron transdermal is safe for you, tell your doctor if you have:

• a stomach or intestinal disorder;
• if you have recently had stomach or intestinal surgery; or
• if you have ever had an allergic reaction to any type of medicated skin patch.

Granisetron transdermal is not expected to harm an unborn baby. Tell your doctor if you are pregnant or plan to become pregnant during treatment.

It is not known whether granisetron transdermal passes into breast milk or if it could harm a nursing baby. Tell your doctor if you are breast-feeding a baby.

Get emergency medical help if you have any of these signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Call your doctor at once if you have:

• fast or pounding heartbeats;
• chest pain;
• severe dizziness;
• increased blood pressure--severe headache, buzzing in your ears, anxiety, confusion, shortness of breath; or
• high levels of serotonin in the body--agitation, hallucinations, fever, fast heart rate, overactive reflexes, nausea, vomiting, diarrhea, loss of coordination, fainting.

Common side effects may include:

• headache, weakness;
• diarrhea, constipation;
• stomach pain, indigestion, loss of appetite;
• sleep problems (insomnia); or
• fever, flu symptoms.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Get emergency medical help if you have signs of an allergic reaction: hives; difficult breathing; swelling of your face, lips, tongue, or throat.

Remove the skin patch and call your doctor at once if you have:

• pain or swelling in your stomach;
• severe redness, itching, swelling, or other irritation where the patch is worn; or
• high levels of serotonin in the body--agitation, hallucinations, fever, fast heart rate, overactive reflexes, nausea, vomiting, diarrhea, loss of coordination, fainting.

Common side effects may include:

• constipation;
• headache; or
• mild skin irritation where the patch was worn.

This is not a complete list of side effects and others may occur. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Granisetron is a prescription medication used to prevent nausea and vomiting caused by cancer chemotherapy and radiation therapy. The injectable form is also used to prevent nausea and vomiting related to surgery.

This medication may be prescribed for other uses. Ask your doctor or pharmacist for more information.

Tell your doctor about all the medicines you take including prescription and non-prescription medicines, vitamins, and herbal supplements. Especially tell your doctor if you take:

• medications that block a protein in the body (CYPA4) such as some macrolide antibiotics (clarithromycin, telithromycin), some HIV protease inhibitors (indinavir, nelfinavir, ritonavir, saquinavir), some HCV protease inhibitors (boceprevir, telaprevir), some azole antifungals (ketoconazole, itraconazole, posaconazole, voriconazole), conivaptan (Vaprisol), delavirdine (Rescriptor), and nefazodone

• medications that increase the activity of the enzyme CYP3A4 such as carbamazepine (Tegretol, Equetro, Carbatrol), phenobarbital, phenytoin (Dilantin), rifampin, St John's wort, and nimodipine (Nimotop)

• medications that could lead to serotonin syndrome such as citalopram (Celexa), escitalopram (Lexapro), fluoxetine (Prozac, Sarafem), fluvoxamine (Luvox), desvenlafaxine (Pristiq), nefazodone (Serzone), paroxetine (Paxil, Pexeva), sertraline (Zoloft), venlafaxine (Effexor), trimipramine (Surmontil), isocarboxazid (Marplan), amitriptyline (Elavil), nortriptyline (Pamelor, Aventyl), protriptyline (Vivactil), and clomipramine (Anafranil), and linezolid (Zyvox)

This is not a complete list of granisetron drug interactions. Ask your doctor or pharmacist for more information.

Medications can interact with certain foods. In some cases, this may be harmful and your doctor may advise you to avoid certain foods. In the case of granisetron, there are no specific foods that you must exclude from your diet when receiving this medication.

• Store granisetron tablets between 15º and 30ºC (59º and 86ºF). Keep container closed tightly. Protect from light.
• Keep this and all medications out of the reach of children.

You should not use this medication if you are allergic to granisetron or to similar medicines such as dolasetron (Anzemet), ondansetron (Zofran), or palonosetron (Aloxi).

Before taking granisetron, tell your doctor if you have liver disease, a heart rhythm disorder, an electrolyte imbalance (such as low levels of potassium or magnesium in your blood), or a personal or family history of Long QT syndrome.

Granisetron is usually started up to 1 hour before chemotherapy. Tell your doctor if you forget to take the medication within the specified amount of time before your procedure.

QT prolongation has been reported with KYTRIL (see PRECAUTIONS and DRUG INTERACTIONS).

Chemotherapy-Induced Nausea and Vomiting

Over 3700 patients have received KYTRIL (granisetron) Tablets in clinical trials with emetogenic cancer therapies consisting primarily of cyclophosphamide or cisplatin regimens.

In patients receiving KYTRIL (granisetron) Tablets 1 mg bid for 1, 7 or 14 days, or 2 mg daily for 1 day, adverse experiences reported in more than 5% of the patients with comparator and placebo incidences are listed in Table 4.

Table 4 Principal Adverse Events in Clinical Trials1

Other adverse events reported in clinical trials were:

Gastrointestinal: In single-day dosing studies in which adverse events were collected for 7 days, nausea (20%) and vomiting (12%) were recorded as adverse events after the 24hour efficacy assessment period.

Hepatic: In comparative trials, elevation of AST and ALT ( > 2 times the upper limit of normal) following the administration of KYTRIL (granisetron) Tablets occurred in 5% and 6% of patients, respectively. These frequencies were not significantly different from those seen with comparators (AST: 2%; ALT: 9%).

Cardiovascular: Hypertension (1%); hypotension, angina pectoris, atrial fibrillation, and syncope have been observed rarely.

Central Nervous System: Dizziness (5%), insomnia (5%), anxiety (2%), somnolence (1%). One case compatible with, but not diagnostic of, extrapyramidal symptoms has been reported in a patient treated with KYTRIL (granisetron) Tablets.

Hypersensitivity: Rare cases of hypersensitivity reactions, sometimes severe (eg, anaphylaxis, shortness of breath, hypotension, urticaria) have been reported.

Other: Fever (5%). Events often associated with chemotherapy also have been reported: leukopenia (9%), decreased appetite (6%), anemia (4%), alopecia (3%), thrombocytopenia (2%).

Over 5000 patients have received injectable KYTRIL (granisetron) in clinical trials.

Table 5 gives the comparative frequencies of the five commonly reported adverse events ( ≥ 3%) in patients receiving KYTRIL (granisetron) Injection, 40 mcg/kg, in single-day chemotherapy trials. These patients received chemotherapy, primarily cisplatin, and intravenous fluids during the 24-hour period following KYTRIL (granisetron) Injection administration.

Table 5 : Principal Adverse Events in Clinical Trials - Single-Day Chemotherapy

In the absence of a placebo group, there is uncertainty as to how many of these events should be attributed to KYTRIL (granisetron) , except for headache, which was clearly more frequent than in comparison groups.

Radiation-Induced Nausea and Vomiting

In controlled clinical trials, the adverse events reported by patients receiving KYTRIL (granisetron) Tablets and concurrent radiation were similar to those reported by patients receiving KYTRIL (granisetron) Tablets prior to chemotherapy. The most frequently reported adverse events were diarrhea, asthenia, and constipation. Headache, however, was less prevalent in this patient population.

Postmarketing Experience

QT prolongation has been reported with KYTRIL (see PRECAUTIONS and DRUG INTERACTIONS).

Read the entire FDA prescribing information for Kytril (Granisetron)

Granisetron blocks the actions of chemicals in the body that can trigger nausea and vomiting.

Granisetron is used to prevent nausea and vomiting that may be caused by medicine to treat cancer (chemotherapy or radiation).

Granisetron may also be used for purposes not listed in this medication guide.

QT prolongation has been reported with Granisetron hydrochloride (see PRECAUTIONS and Drug Interactions).

Chemotherapy-Induced Nausea and Vomiting

Over 3700 patients have received Granisetron hydrochloride tablets in clinical trials with emetogenic cancer therapies consisting primarily of cyclophosphamide or cisplatin regimens.

In patients receiving Granisetron hydrochloride tablets 1 mg twice a day for 1, 7 or 14 days, or 2 mg daily for 1 day, adverse experiences reported in more than 5% of the patients with comparator and placebo incidences are listed in Table 4.

1Adverse events were recorded for 7 days when Granisetron hydrochloride tablets were given on a single day and for up to 28 days when Granisetron hydrochloride tablets were administered for 7 or 14 days.

2Metoclopramide/dexamethasone; phenothiazines/dexamethasone; dexamethasone alone; prochlorperazine.

Other adverse events reported in clinical trials were:

Gastrointestinal: In single-day dosing studies in which adverse events were collected for 7 days, nausea (20%) and vomiting (12%) were recorded as adverse events after the 24 hour efficacy assessment period.

Hepatic: In comparative trials, elevation of AST and ALT (>2 times the upper limit of normal) following the administration of Granisetron hydrochloride tablets occurred in 5% and 6% of patients, respectively. These frequencies were not significantly different from those seen with comparators (AST: 2%; ALT: 9%).

Cardiovascular: Hypertension (1%); hypotension, angina pectoris, atrial fibrillation, and syncope have been observed rarely.

Central Nervous System: Dizziness (5%), insomnia (5%), anxiety (2%), somnolence (1%). One case compatible with, but not diagnostic of, extrapyramidal symptoms has been reported in a patient treated with Granisetron hydrochloride tablets.

Hypersensitivity: Rare cases of hypersensitivity reactions, sometimes severe (e.g., anaphylaxis, shortness of breath, hypotension, urticaria) have been reported.

Other: Fever (5%). Events often associated with chemotherapy also have been reported: leukopenia (9%), decreased appetite (6%), anemia (4%), alopecia (3%), thrombocytopenia (2%).

Over 5000 patients have received injectable Granisetron hydrochloride in clinical trials.

Table 5 gives the comparative frequencies of the five commonly reported adverse events (3%) in patients receiving Granisetron hydrochloride injection, 40 mcg/kg, in single-day chemotherapy trials. These patients received chemotherapy, primarily cisplatin, and intravenous fluids during the 24 hour period following Granisetron hydrochloride injection administration.

1 Adverse events were generally recorded over 7 days post-Granisetron hydrochloride injection administration.

2 Metoclopramide/dexamethasone and phenothiazines/dexamethasone.

In the absence of a placebo group, there is uncertainty as to how many of these events should be attributed to Granisetron hydrochloride, except for headache, which was clearly more frequent than in comparison groups.

Radiation-Induced Nausea and Vomiting

In controlled clinical trials, the adverse events reported by patients receiving Granisetron hydrochloride tablets and concurrent radiation were similar to those reported by patients receiving Granisetron hydrochloride tablets prior to chemotherapy. The most frequently reported adverse events were diarrhea, asthenia, and constipation. Headache, however, was less prevalent in this patient population.

Postmarketing Experience

QT prolongation has been reported with Granisetron hydrochloride (see PRECAUTIONS and Drug Interactions).

There is no specific treatment for Granisetron hydrochloride overdosage. In case of overdosage, symptomatic treatment should be given. Overdosage of up to 38.5 mg of Granisetron hydrochloride injection has been reported without symptoms or only the occurrence of a slight headache.

(gra NI se tron)

• Antiemetic
• Selective 5-HT3 Receptor Antagonist

Chemotherapy-associated nausea and vomiting: Prevention of nausea and vomiting associated with initial and repeat courses of emetogenic chemotherapy, including high-dose cisplatin (injection and tablets); prevention of nausea and vomiting associated with anthracycline/cyclophosphamide chemotherapy regimens; prevention of nausea and vomiting associated with moderately and/or highly emetogenic chemotherapy regimens of up to 5 consecutive days of duration (transdermal).

Radiation-associated nausea and vomiting: Prevention of nausea and vomiting associated with radiation therapy, including total body radiation and fractionated abdominal radiation (tablets).

Hypersensitivity to granisetron or any component of the formulation or to other 5-HT3 receptor antagonists

Canadian labeling: Additional contraindications (not in US labeling): Concomitant use with apomorphine

Note: Granisol oral solution has been discontinued in the US for more than 1 year.

Prevention of chemotherapy-associated nausea and vomiting: Children ≥2 years and Adolescents: IV: 10 mcg/kg 30 minutes prior to chemotherapy; only on the day(s) chemotherapy is given.

Pediatric guideline recommendations:

Prevention of chemotherapy-induced nausea and vomiting (off-label dosing; Dupuis 2013):

Highly emetogenic chemotherapy: Infants ≥1 month and Children <12 years: IV: 40 mcg/kg as a single daily dose prior to chemotherapy. Antiemetic regimen also includes dexamethasone.

Highly emetogenic chemotherapy: Children ≥12 years and Adolescents: IV: 40 mcg/kg as a single daily dose prior to chemotherapy. Antiemetic regimen includes dexamethasone and (if no known or suspected drug interactions) aprepitant.

Moderately emetogenic chemotherapy: Infants ≥1 month, Children, and Adolescents:

IV: 40 mcg/kg as a single daily dose. Antiemetic regimen also includes dexamethasone

Oral: 40 mcg/kg every 12 hours. Antiemetic regimen also includes dexamethasone

Low emetogenic chemotherapy: Infants ≥1 month, Children, and Adolescents:

IV: 40 mcg/kg as a single daily dose.

Oral: 40 mcg/kg every 12 hours.

IV, Oral, Transdermal: No dosage adjustment necessary.

SubQ (extended-release injection):

CrCl ≥60 mL/minute: No dosage adjustment necessary.

CrCl 30 to 59 mL/minute: 10 mg on day 1 of chemotherapy; do not administer more frequently than once every 14 days.

CrCl <30 mL/minute: Avoid use.

Oral: Doses should be given up to 1 hour prior to initiation of chemotherapy/radiation

IV: Administer IV push over 30 seconds or as a 5-minute infusion

SubQ (extended-release injection): For subcutaneous administration only. Administer as a single injection at the back of the upper arm or in abdomen (at least one inch away from the umbilicus). Avoid using areas where the skin is burned, hardened, inflamed, swollen, or otherwise compromised. Inject slowly; may take up to 20 to 30 seconds (product is viscous, pressing the syringe plunger will not result in faster expulsion). A topical anesthetic may be applied at injection site prior to administration. Do not administer if particulate matter or discoloration is observed, if the tip cap is missing or has been tampered with, or the luer fitting is missing or dislodged. Remove from refrigerator at least 60 minutes prior to administration; remove from pack and activate 1 syringe warming pouch and wrap syringe with warming pouch for 5 to 6 minutes to allow warming to body temperature. Injection site reactions may occur; if injection site reaction is not yet resolved prior to the next dose, rotate injection site with next administration.

Transdermal (Sancuso): Apply patch to clean, dry, intact skin on upper outer arm. Do not use on red, irritated, or damaged skin. Remove patch from pouch immediately before application. Do not cut patch. Cover patch application site with clothing to protect from natural or artificial sunlight exposure while patch is applied and for 10 days following removal; granisetron may potentially be affected by natural or artificial sunlight. Do not apply heat (eg, heating pad) over or in area of the transdermal patch; avoid prolonged exposure to heat (may increase plasma concentrations).

Adverse events have not been observed in animal reproduction studies. In an ex vivo placental perfusion study, granisetron was shown to cross the placenta in a concentration (dose) dependent manner (Julius 2014). Initial studies note the pharmacokinetics of the transdermal system may be different in pregnant women. A relationship between granisetron plasma concentrations and relief of symptoms of nausea and vomiting of pregnancy was also observed (Cartis 2016). Some dosage forms (injection) may contain benzyl alcohol.

Applies to granisetron: intravenous solution

Other dosage forms:

• transdermal patch extended release

Along with its needed effects, granisetron may cause some unwanted effects. Although not all of these side effects may occur, if they do occur they may need medical attention.

Check with your doctor or nurse immediately if any of the following side effects occur while taking granisetron:

• Blurred vision
• fever
• nervousness
• pounding in the ears
• slow or fast heartbeat

• Arm, back, or jaw pain
• chest pain or discomfort
• chest tightness or heaviness
• confusion
• dizziness, faintness, or lightheadedness when getting up suddenly from a lying or sitting position
• fainting
• irregular heartbeat
• nausea
• shortness of breath
• skin rash, hives, and itching
• sweating

Some side effects of granisetron may occur that usually do not need medical attention. These side effects may go away during treatment as your body adjusts to the medicine. Also, your health care professional may be able to tell you about ways to prevent or reduce some of these side effects. Check with your health care professional if any of the following side effects continue or are bothersome or if you have any questions about them:

• Abdominal or stomach pain
• diarrhea
• difficulty having a bowel movement (stool)
• headache
• lack or loss of strength
• unusual tiredness or weakness
• vomiting

• Agitation
• dizziness
• drowsiness
• fear
• heartburn
• indigestion
• sleepiness or unusual drowsiness
• sour stomach
• trouble with sleeping
• unusual taste in the mouth

Greater than or equal to 2 to 16 years: 10 mcg/kg IV 30 minutes before start of chemotherapy.

Study (n=80)
Randomized double-blind clinical studies have used granisetron injection in the range of 10 to 40 mcg/kg.

No adjustments recommended