Granisetron Hydrochloride 1 mg Tablet, Film Coated, 20-count — NDC 69452-350-11 (Billing 69452-0350-11)
This is a package of 20 tablets of Granisetron Hydrochloride 1 mg Tablet, Film Coated from Bionpharma Inc., marketed since Feb 2022 and currently FDA-listed; retail pharmacies pay about $1.31 per tablet (NADAC).
NDC database record
One package, one record: these facts belong to NDC 69452-350-11 alone.
- Record
- FDA NDC Directory package listing · Human prescription drug
- Code segments
- 69452 labeler · 350 product · 11 package
- Package marketed since
- Feb 28, 2022
- Sample package
- No — commercial package
- Listing certified through
- Dec 31, 2026
- Billing quantity
- 20 EA per package
- Barcode (UPC-A, from the NDC)
- 3 6945235011 9
- Medicaid fills, this package
- 882 prescriptions in the last four reported quarters
- FDA record last changed
- Jul 24, 2026
Identity & classification
Regulatory identifiers FDA, NLM and CMS codes for this package
Drug-database identifiers Medi-Span GPI and First Databank GCN / HICL / AHFS classification
- GSN (GCN sequence number): 021592
- GCN: 06019
- GPI-14 (Medi-Span): 50250035100310
- HICL (First Databank): 007611
- AHFS class code: 56:22.20.00
- RxCUI (RxNorm): 310599
Where does this data come from?
- FDA openFDA NDC Directory · synced Oct 1, 2026
- FDA label on DailyMed · label index refreshed Oct 5, 2026
- RxNorm (NLM RxNav) · catalog refreshed Oct 1, 2026
- Medi-Span GPI (licensed)
- First Databank (licensed) · refreshed Oct 1, 2026
RxNorm drug class
This medicine belongs to the Serotonin-3 Receptor Antagonist class.
Where does this data come from?
- RxClass (NLM) · catalog refreshed Oct 1, 2026
Clinical
Granisetron is used to prevent nausea and vomiting caused by cancer chemotherapy and radiation therapy. Granisetron is in a class of medications called 5-HT3 receptor antagonists. It works by blocking serotonin, a natural substance that may cause nausea and vomiting.
Read the full MedlinePlus article ↗- Granisetron is an anti-nausea medicine. It's mainly used to prevent nausea and vomiting that cancer chemotherapy or radiation therapy can cause. Depending on which product you've b...
- The Sancuso patch delivers granisetron slowly through your skin over up to 7 days — you apply it to your upper outer arm at least 24 hours before chemotherapy starts and leave it o...
- How does the Sancuso patch work differently from the pill or injection?
- The most common ones are headache and constipation — these are the side effects most often reported in clinical studies. Some people also notice fever, stomach pain, or a slight ch...
Patient education
Supplement & herbal interactions
Where does this data come from?
- MedlinePlus (NLM) · refreshed Oct 1, 2026
- FDA label on DailyMed · label index refreshed Oct 5, 2026
Ask a licensed pharmacist directly — free, answered by our team.
Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per ea | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | $1.305 | $26.10 / 20 tablets |
| Medicaid paysCMS SDUD · 12 mo | $1.63 | $32.62 / 20 tablets |
| Medicare drug plans payPart D · Q2 2026 | $2.07 | $41.44 / 20 tablets |
| Medicare Part B allowsASP · Q0166 | No ASP payment limit on file for Q0166 this quarter. | |
Where does this data come from?
- CMS NADAC weekly file · file of Sep 30, 2026
- CMS ASP pricing files · refreshed Sep 20, 2026
- CMS Medicaid State Drug Utilization Data · through Q4 2025
- CMS Part D plan pricing files · refreshed Sep 24, 2026
- VA National Acquisition Center price file
Billing & reimbursement
Where does this data come from?
- CMS ASP NDC-HCPCS crosswalk · refreshed Sep 22, 2026
- DMEPDAC NDC-HCPCS crosswalk
- openFDA NSDE billing units · refreshed Sep 7, 2026
Packaging — all sizes for this product
| Package NDC | Description | Per unit | Per pack | Marketing start | Marketing end | Status |
|---|---|---|---|---|---|---|
| 69452-0350-01 69452-350-01 | 2 BLISTER PACK in 1 CARTON / 1 TABLET, FILM COATED in 1 BLISTER PACK | $1.31 / ea | $2.61 | 2022-02-28 | — | Active |
| 69452-0350-11 You're viewing this | 20 TABLET, FILM COATED in 1 BOTTLE, PLASTIC | $1.31 / ea | $26.10 | 2022-02-28 | — | Active |
| 69452-0350-92 69452-350-92 Main listing | 2 BLISTER PACK in 1 CARTON / 10 TABLET, FILM COATED in 1 BLISTER PACK | $1.31 / ea | $26.10 | 2022-02-28 | — | Active |
This pack effectively ties for the lowest per-ea cost of the 3 priced pack sizes ($1.31 NADAC).
This pack accounts for about 32% of this product's recent Medicaid fills; most go to a different pack size. See all packs ↓
Pack size FAQ
What quantity is in this package?
What NDC number is used to bill for this package of Granisetron Hydrochloride 1 mg Tablet, Film Coated?
Prices are the latest CMS NADAC pharmacy acquisition cost per NDC; per-pack figures are per-unit × pack quantity, shown only when the pack is denominated in the same measure NADAC prices.
Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Granisetron Hydrochloride 1 mg 51991-0735-20 | Breckenridge | 20 tablets | $1.305 | AB | Availability likely | — |
| Granisetron Hydrochloride 1 mgthis 69452-0350-11 | Bionpharma | 20 tablets | $1.305 | AB | Availability likely | — |
| Granisetron hydrochloride 1 mg 63850-0005-01 | Natco | 10 tablets | — | AB | FDA listed | — |
Where does this data come from?
- FDA openFDA NDC Directory · synced Oct 1, 2026
- FDA Orange Book · refreshed Oct 3, 2026
- CMS NADAC weekly file · file of Sep 30, 2026
Availability & generic status
This product is an FDA-approved generic. Other versions of the same drug are listed under Therapeutic equivalents, least expensive first.
Where does this data come from?
- FDA Orange Book · refreshed Oct 3, 2026
What it looks like
Where does this data come from?
- FDA label on DailyMed · label index refreshed Oct 5, 2026
Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
🧪 Avoiding an ingredient? See Granisetron inactive ingredients by manufacturer: every current product's list side by side, so you can ask your pharmacy for the version that does not list it.
💡 Tap an ingredient (hover on desktop) to see what it is and why it’s used.
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UNII OP1R32D61U
Microcrystalline cellulose is a purified form of cellulose, a natural fiber from plant sources. It acts as a binder and filler in tablets and capsules, helping hold ingredients together and give the medicine its shape and size.
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UNII 0VUT3PMY82
Hypromellose 2910 is a plant-derived thickening agent made from cellulose. In medicines, it forms protective coatings on tablets or capsules, controls how fast the drug releases, and thickens liquid formulations.
-
UNII EWQ57Q8I5X
Lactose monohydrate is a natural sugar derived from milk. It serves as a filler and binder in tablets and capsules, helping create the proper size, texture, and consistency of the medicine.
-
UNII 70097M6I30
Magnesium stearate is a salt made from magnesium and stearic acid, a fatty substance. It's used in tablets and capsules as a lubricant and glidant to help ingredients flow smoothly during manufacturing and prevent sticking.
-
UNII 5856J3G2A2
A starch-based powder made from potatoes and processed with sodium. It acts as a disintegrant, helping the tablet or capsule break apart quickly in the stomach so the medicine can be absorbed.
5 inactive ingredients listed in the exact product block matched to this NDC.
Where does this data come from?
ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.- FDA label on DailyMed · label index refreshed Oct 5, 2026
- FDA openFDA NDC Directory · synced Oct 1, 2026
Inactive ingredient FAQ
Are inactive ingredients the same for every manufacturer?
Why might an inactive ingredient be missing?
Can inactive ingredients matter?
Manufacturer & labeler
More NDCs from Bionpharma Inc. labeler code 69452
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- Ropinirole 2 mg Tablet, Film Coated NDC 69452-359-20
Where does this data come from?
- FDA openFDA NDC Directory · synced Oct 1, 2026
- Drugs@FDA
Full prescribing information FDA SPL
🎯 Indications and Usage ▾
INDICATIONS AND USAGE Granisetron hydrochloride tablets are indicated for the prevention of: Nausea and vomiting associated with initial and repeat courses of emetogenic cancer therapy, including high-dose cisplatin. Nausea and vomiting associated with radiation, including total body irradiation and fractionated abdominal radiation.
⏱️ Dosage and Administration ▾
DOSAGE AND ADMINISTRATION Emetogenic Chemotherapy The recommended adult dosage of oral granisetron hydrochloride is 2 mg once daily or 1 mg twice daily. In the 2 mg once-daily regimen, two 1 mg tablets are given up to 1 hour before chemotherapy. In the 1 mg twice-daily regimen, the first 1 mg tablet is given up to 1 hour before chemotherapy, and the second tablet, 12 hours after the first.
Either regimen is administered only on the day(s) chemotherapy is given. Continued treatment, while not on chemotherapy, has not been found to be useful. Use in the Elderly, Renal Failure Patients or Hepatically Impaired Patients No dosage adjustment is recommended (see CLINICAL PHARMACOLOGY: Pharmacokinetics ).
Pediatric Use Safety and effectiveness in pediatric patients have not been established. Radiation (Either Total Body Irradiation or Fractionated Abdominal Radiation) The recommended adult dosage of oral granisetron hydrochloride is 2 mg once daily. Two 1 mg tablets are taken within 1 hour of radiation.
Pediatric Use Safety and effectiveness in pediatric patients have not been established. Use in the Elderly No dosage adjustment is recommended.
⛔ Contraindications ▾
CONTRAINDICATIONS Granisetron hydrochloride is contraindicated in patients with known hypersensitivity to the drug or any of its components.
⚠️ Warnings ▾
WARNINGS Serotonin Syndrome The development of serotonin syndrome has been reported with 5-HT 3 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 intravenous methylene blue). Some of the reported cases were fatal.
Serotonin syndrome occurring with overdose of another 5-HT 3 receptor antagonist alone has also been reported. The majority of reports of serotonin syndrome related to 5-HT 3 receptor antagonist use occurred in a post-anesthesia care unit or an infusion center. Symptoms associated with serotonin syndrome may include the following combination of signs and symptoms: mental 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, with or without gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea).
Patients should be monitored for the emergence of serotonin syndrome, especially with concomitant use of granisetron and other serotonergic drugs. If symptoms of serotonin syndrome occur, discontinue granisetron and initiate supportive treatment. Patients should be informed of the increased risk of serotonin syndrome, especially if granisetron is used concomitantly with other serotonergic drugs ( see Drug Interactions , Patient Counseling Information ).
🤒 Adverse Reactions ▾
ADVERSE REACTIONS 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 inTable 4.
Table 4 Principal Adverse Events in Clinical Trials Percent of Patients With Event Granisetron Hydrochloride 1 Tablets 1 mg twice a day (n=978) Granisetron Hydrochloride 1 Tablets 2 mg once a day (n=1450) Comparator 2 (n=599) Placebo (n=185) Headache 21% 20% 13% 12% Constipation 18% 14% 16% 8% Asthenia 14% 18% 10% 4% Diarrhea 8% 9% 10% 4% Abdominal pain 6% 4% 6% 3% Dyspepsia 4% 6% 5% 4% 1 Adverse 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.
2 Metoclopramide/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. Table 5 Principal Adverse Events in Clinical Trials - Single-Day Chemotherapy Percent of Patients with Event Granisetron Hydrochloride Injection 1 40 mcg/kg (n=1268) Comparator 2 (n=422) Headache 14% 6% Asthenia 5% 6% Somnolence 4% 15% Diarrhea 4% 6% Constipation 3% 3% 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 repor… [Excerpted — this section continues on DailyMed.]
🔄 Drug Interactions ▾
Drug Interactions Granisetron does not induce or inhibit the cytochrome P-450 drug-metabolizing enzyme system in vitro . There have been no definitive drug-drug interaction studies to examine pharmacokinetic or pharmacodynamic interaction with other drugs; however, in humans, granisetron hydrochloride injection has been safely administered with drugs representing benzodiazepines, neuroleptics, and anti-ulcer medications commonly prescribed with antiemetic treatments. Granisetron hydrochloride injection also does not appear to interact with emetogenic cancer chemotherapies.
Because granisetron is metabolized by hepatic cytochrome P-450 drug-metabolizing enzymes, inducers or inhibitors of these enzymes may change the clearance and, hence, the half-life of granisetron. No specific interaction studies have been conducted in anesthetized patients. In addition, the activity of the cytochrome P-450 subfamily 3A4 (involved in the metabolism of some of the main narcotic analgesic agents) is not modified by granisetron hydrochloride in vitro .
In in vitro human microsomal studies, ketoconazole inhibited ring oxidation of granisetron hydrochloride. However, the clinical significance of in vivo pharmacokinetic interactions with ketoconazole is not known. In a human pharmacokinetic study, hepatic enzyme induction with phenobarbital resulted in a 25% increase in total plasma clearance of intravenous granisetron hydrochloride.
The clinical significance of this change is not known. QT prolongation has been reported with granisetron hydrochloride. Use of granisetron hydrochloride in patients concurrently treated with drugs known to prolong the QT interval and/or are arrhythmogenic, this may result in clinical consequences.
Serotonin syndrome (including altered mental status, autonomic instability, and neuromuscular symptoms) has been described following the concomitant use of 5-HT 3 receptor antagonists and other serotonergic drugs, including selective serotonin reuptake inhibitors (SSRIs) and serotonin and noradrenaline reuptake inhibitors (SNRIs) ( see WARNINGS ).
🤰 Pregnancy ▾
Pregnancy Teratogenic Effects Pregnancy Category B . Reproduction studies have been performed in pregnant rats at oral doses up to 125 mg/kg/day (750 mg/m 2 /day, 507 times the recommended human dose based on body surface area) and pregnant rabbits at oral doses up to 32 mg/kg/day (378 mg/m 2 /day, 255 times the recommended human dose based on body surface area) and have revealed no evidence of impaired fertility or harm to the fetus due to granisetron. There are, however, no adequate and well-controlled studies in pregnant women.
Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.
🧒 Pediatric Use ▾
Pediatric Use Safety and effectiveness in pediatric patients have not been established.
🧓 Geriatric Use ▾
Geriatric Use During clinical trials, 325 patients 65 years of age or older received granisetron hydrochloride tablets; 298 were 65 to 74 years of age, and 27 were 75 years of age or older. Efficacy and safety were maintained with increasing age.
🆘 Overdosage ▾
OVERDOSAGE 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.
🧬 Clinical Pharmacology ▾
CLINICAL PHARMACOLOGY Granisetron is a selective 5-hydroxytryptamine 3 (5-HT 3 ) receptor antagonist with little or no affinity for other serotonin receptors, including 5-HT 1 ; 5-HT 1A ; 5-HT 1B/C ; 5-HT 2 ; for α 1- , α 2- , or β-adrenoreceptors; for dopamine-D 2 ; or for histamine-H 1 ; benzodiazepine; picrotoxin or opioid receptors. Serotonin receptors of the 5-HT 3 type are located peripherally on vagal nerve terminals and centrally in the chemoreceptor trigger zone of the area postrema. During chemotherapy that induces vomiting, mucosal enterochromaffin cells release serotonin, which stimulates 5-HT 3 receptors.
This evokes vagal afferent discharge, inducing vomiting. Animal studies demonstrate that, in binding to 5-HT 3 receptors, granisetron blocks serotonin stimulation and subsequent vomiting after emetogenic stimuli such as cisplatin. In the ferret animal model, a single granisetron injection prevented vomiting due to high-dose cisplatin or arrested vomiting within 5 to 30 seconds.
In most human studies, granisetron has had little effect on blood pressure, heart rate or ECG. No evidence of an effect on plasma prolactin or aldosterone concentrations has been found in other studies. Following single and multiple oral doses, granisetron hydrochloride tablets slowed colonic transit in normal volunteers.
However, granisetron hydrochloride had no effect on oro-cecal transit time in normal volunteers when given as a single intravenous (IV) infusion of 50 mcg/kg or 200 mcg/kg. Pharmacokinetics In healthy volunteers and adult cancer patients undergoing chemotherapy, administration of granisetron hydrochloride tablets produced mean pharmacokinetic data shown in Table 1 . Table 1 Pharmacokinetic Parameters (Median [range]) Following Granisetron Hydrochloride Tablets Peak Plasma Concentration (ng/mL) Terminal Phase Plasma Half-Life (h) Volume of Distribution (L/kg) Total Clearance (L/h/kg) Cancer Patients 1 mg twice a day, 7 days (n=27) 5.99 [0.63 to 30.9] N.D.
1 N.D. 0.52 [0.09 to 7.37] Volunteers single 1 mg dose (n=39) 3.63 [0.27 to 9.14] 6.23 [0.96 to 19.9] 3.94 [1.89 to 39.4] 0.41 [0.11 to 24.6] 1 Not determined after oral administration; following a single intravenous dose of 40 mcg/kg, terminal phase half-life was determined to be 8.95 hours. N.D.
Not determined. Absorption When granisetron hydrochloride tablets were administered with food, AUC was decreased by 5% and C max increased by 30% in non-fasted healthy volunteers who received a single dose of 10 mg. Distribution Plasma protein binding is approximately 65% and granisetron distributes freely between plasma and red blood cells.
Metabolism Granisetron metabolism involves N-demethylation and aromatic ring oxidation followed by conjugation. In vitro liver microsomal studies show that granisetron's major route of metabolism is inhibited by ketoconazole, suggestive of metabolism mediated by the cytochrome P-450 3A subfamily. Animal studies suggest that some of the metabolites may also have 5-HT 3 receptor antagonist activity.
Elimination Clearance is predominantly by hepatic metabolism. In normal volunteers, approximately 11% of the orally administered dose is eliminated unchanged in the urine in 48 hours. The remainder of the dose is excreted as metabolites, 48% in the urine and 38% in the feces.
Subpopulations Gender The effects of gender on the pharmacokinetics of granisetron hydrochloride tablets have not been studied. However, after intravenous infusion of granisetron hydrochloride, no difference in mean AUC was found between males and females, although males had a higher C max generally. In elderly and pediatric patients and in patients with renal failure or hepatic impairment, the pharmacokinetics of granisetron was determined following administration of intravenous granisetron hydrochloride.
Elderly The ranges of the pharmacokinetic parameters in elderly volunteers (mean age 71 years), given a single 40 mcg/kg intravenous dose of granisetron hydrochloride inject… [Excerpted — this section continues on DailyMed.]
📦 How Supplied / Storage and Handling ▾
HOW SUPPLIED White to off-white film coated triangular shaped biconvex tablet debossed with “G1” on one side and plain on the other side. 1 mg Bottle of 20 Tablets: NDC 69452-350-11 1 mg Unit of Use 2s: NDC 69452-350-01 1 mg 20 (2 x 10) Unit Dose Tablets: NDC 69452-350-92 (intended for institutional use only) Storage Store between 20° and 25°C (68° and 77°F). [see USP Controlled Room Temperature]. Keep container closed tightly. Protect from light.
📋 Description ▾
DESCRIPTION Granisetron hydrochloride tablets USP contain granisetron hydrochloride USP, an antinauseant and antiemetic agent. Chemically it is endo -N-(9-methyl-9-azabicyclo [3.3.1] non-3-yl)-1-methyl-1H-indazole-3-carboxamide hydrochloride with a molecular weight of 348.9 (312.4 free base). Its empirical formula is C 18 H 24 N 4 O•HCl, while its chemical structure is: Granisetron hydrochloride USP is a white to off-white solid that is readily soluble in water and normal saline at 20ºC.
Each white to off-white film coated triangular shaped biconvex tablet contains 1.12 mg granisetron hydrochloride USP equivalent to granisetron, 1 mg. Inactive ingredients are: microcrystalline cellulose, sodium starch glycolate, lactose monohydrate, hypromellose, magnesium stearate and opadry white. The components of opadry white are hypromellose, titanium dioxide, polyethylene glycol 6000 and polysorbate 80. structure
⚠️ Precautions ▾
PRECAUTIONS Granisetron hydrochloride is not a drug that stimulates gastric or intestinal peristalsis. It should not be used instead of nasogastric suction. The use of granisetron hydrochloride in patients following abdominal surgery or in patients with chemotherapy-induced nausea and vomiting may mask a progressive ileus and/or gastric distention.
An adequate QT assessment has not been conducted, but QT prolongation has been reported with granisetron hydrochloride. Therefore, granisetron hydrochloride should be used with caution in patients with pre-existing arrhythmias or cardiac conduction disorders, as this might lead to clinical consequences. Patients with cardiac disease, on cardio-toxic chemotherapy, with concomitant electrolyte abnormalities and/or on concomitant medications that prolong the QT interval are particularly at risk.
Drug Interactions Granisetron does not induce or inhibit the cytochrome P-450 drug-metabolizing enzyme system in vitro . There have been no definitive drug-drug interaction studies to examine pharmacokinetic or pharmacodynamic interaction with other drugs; however, in humans, granisetron hydrochloride injection has been safely administered with drugs representing benzodiazepines, neuroleptics, and anti-ulcer medications commonly prescribed with antiemetic treatments. Granisetron hydrochloride injection also does not appear to interact with emetogenic cancer chemotherapies.
Because granisetron is metabolized by hepatic cytochrome P-450 drug-metabolizing enzymes, inducers or inhibitors of these enzymes may change the clearance and, hence, the half-life of granisetron. No specific interaction studies have been conducted in anesthetized patients. In addition, the activity of the cytochrome P-450 subfamily 3A4 (involved in the metabolism of some of the main narcotic analgesic agents) is not modified by granisetron hydrochloride in vitro .
In in vitro human microsomal studies, ketoconazole inhibited ring oxidation of granisetron hydrochloride. However, the clinical significance of in vivo pharmacokinetic interactions with ketoconazole is not known. In a human pharmacokinetic study, hepatic enzyme induction with phenobarbital resulted in a 25% increase in total plasma clearance of intravenous granisetron hydrochloride.
The clinical significance of this change is not known. QT prolongation has been reported with granisetron hydrochloride. Use of granisetron hydrochloride in patients concurrently treated with drugs known to prolong the QT interval and/or are arrhythmogenic, this may result in clinical consequences.
Serotonin syndrome (including altered mental status, autonomic instability, and neuromuscular symptoms) has been described following the concomitant use of 5-HT 3 receptor antagonists and other serotonergic drugs, including selective serotonin reuptake inhibitors (SSRIs) and serotonin and noradrenaline reuptake inhibitors (SNRIs) ( see WARNINGS ). Carcinogenesis, Mutagenesis, Impairment of Fertility In a 24 month carcinogenicity study, rats were treated orally with granisetron 1, 5 or 50 mg/kg/day (6, 30 or 300 mg/m 2 /day).
The 50 mg/kg/day dose was reduced to 25 mg/kg/day (150 mg/m 2 /day) during week 59 due to toxicity. For a 50 kg person of average height (1.46 m 2 body surface area), these doses represent 4, 20, and 101 times the recommended clinical dose (1.48 mg/m 2 , oral) on a body surface area basis. There was a statistically significant increase in the incidence of hepatocellular carcinomas and adenomas in males treated with 5 mg/kg/day (30 mg/m 2 /day, 20 times the recommended human dose based on body surface area) and above, and in females treated with 25 mg/kg/day (150 mg/m 2 /day, 101 times the recommended human dose based on body surface area).
No increase in liver tumors was observed at a dose of 1 mg/kg/day (6 mg/m 2 /day, 4 times the recommended human dose based on body surface area) in males and 5 mg/kg/day (30 mg/m 2 /day, 20 times the recommended human dose based on body… [Excerpted — this section continues on DailyMed.]
🍼 Nursing Mothers ▾
Nursing Mothers It is not known whether granisetron is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when granisetron hydrochloride is administered to a nursing woman.
🧬 Pharmacokinetics ▾
Pharmacokinetics In healthy volunteers and adult cancer patients undergoing chemotherapy, administration of granisetron hydrochloride tablets produced mean pharmacokinetic data shown in Table 1 . Table 1 Pharmacokinetic Parameters (Median [range]) Following Granisetron Hydrochloride Tablets Peak Plasma Concentration (ng/mL) Terminal Phase Plasma Half-Life (h) Volume of Distribution (L/kg) Total Clearance (L/h/kg) Cancer Patients 1 mg twice a day, 7 days (n=27) 5.99 [0.63 to 30.9] N.D. 1 N.D.
0.52[0.09 to 7.37] Volunteers single 1 mg dose (n=39) 3.63 [0.27 to 9.14] 6.23 [0.96 to 19.9] 3.94 [1.89 to 39.4] 0.41 [0.11 to 24.6] 1 Not determined after oral administration; following a single intravenous dose of 40 mcg/kg, terminal phase half-life was determined to be 8.95 hours. N.D. Not determined.
Absorption When granisetron hydrochloride tablets were administered with food, AUC was decreased by 5% and C max increased by 30% in non-fasted healthy volunteers who received a single dose of 10 mg. Distribution Plasma protein binding is approximately 65% and granisetron distributes freely between plasma and red blood cells. Metabolism Granisetron metabolism involves N-demethylation and aromatic ring oxidation followed by conjugation.
In vitro liver microsomal studies show that granisetron's major route of metabolism is inhibited by ketoconazole, suggestive of metabolism mediated by the cytochrome P-450 3A subfamily. Animal studies suggest that some of the metabolites may also have 5-HT 3 receptor antagonist activity. Elimination Clearance is predominantly by hepatic metabolism.
In normal volunteers, approximately 11% of the orally administered dose is eliminated unchanged in the urine in 48 hours. The remainder of the dose is excreted as metabolites, 48% in the urine and 38% in the feces. Subpopulations Gender The effects of gender on the pharmacokinetics of granisetron hydrochloride tablets have not been studied.
However, after intravenous infusion of granisetron hydrochloride, no difference in mean AUC was found between males and females, although males had a higher C max generally. In elderly and pediatric patients and in patients with renal failure or hepatic impairment, the pharmacokinetics of granisetron was determined following administration of intravenous granisetron hydrochloride. Elderly The ranges of the pharmacokinetic parameters in elderly volunteers (mean age 71 years), given a single 40 mcg/kg intravenous dose of granisetron hydrochloride injection, were generally similar to those in younger healthy volunteers; mean values were lower for clearance and longer for half-life in the elderly.
Renal Failure Patients Total clearance of granisetron was not affected in patients with severe renal failure who received a single 40 mcg/kg intravenous dose of granisetron hydrochloride injection. Hepatically Impaired Patients A pharmacokinetic study with intravenous granisetron hydrochloride in patients with hepatic impairment due to neoplastic liver involvement showed that total clearance was approximately halved compared to patients without hepatic impairment. Given the wide variability in pharmacokinetic parameters noted in patients, dosage adjustment in patients with hepatic functional impairment is not necessary.
Pediatric Patients A pharmacokinetic study in pediatric cancer patients (2 to 16 years of age), given a single 40 mcg/kg intravenous dose of granisetron hydrochloride injection, showed that volume of distribution and total clearance increased with age. No relationship with age was observed for peak plasma concentration or terminal phase plasma half-life. When volume of distribution and total clearance are adjusted for body weight, the pharmacokinetics of granisetron are similar in pediatric and adult cancer patients.
🔬 Clinical Studies ▾
CLINICAL TRIALS Chemotherapy-Induced Nausea and Vomiting Granisetron hydrochloride tablets prevent nausea and vomiting associated with initial and repeat courses of emetogenic cancer therapy, as shown by 24 hour efficacy data from studies using both moderately- and highly-emetogenic chemotherapy. Moderately Emetogenic Chemotherapy The first trial compared granisetron hydrochloride tablets doses of 0.25 mg to 2 mg twice a day, in 930 cancer patients receiving, principally, cyclophosphamide, carboplatin, and cisplatin (20 mg/m 2 to 50 mg/m 2 ).
Efficacy was based on complete response (i.e., no vomiting, no moderate or severe nausea, no rescue medication), no vomiting, and no nausea. Table 2 summarizes the results of this study. Table 2 Prevention of Nausea and Vomiting 24 Hours Post-Chemotherapy 1 Percentages of Patients Granisetron Hydrochloride Tablet Dose Efficacy Measures 0.25 mg twice a day (n=229) % 0.5 mg twice a day (n=235) % 1 mg twice a day (n=233) % 2 mg twice a day (n=233) % Complete Response 2 61 70* 81*† 72* No Vomiting 66 77* 88* 79* No Nausea 48 57 63* 54 1 Chemotherapy included oral and injectable cyclophosphamide, carboplatin, cisplatin (20 mg/m 2 to 50 mg/m 2 ), dacarbazine, doxorubicin, epirubicin.
2 No vomiting, no moderate or severe nausea, no rescue medication. *Statistically significant (P<0.01) vs. 0.25 mg twice a day. †Statistically significant (P<0.01) vs. 0.5 mg twice a day.
Results from a second double-blind, randomized trial evaluating granisetron hydrochloride tablets 2 mg once a day and granisetron hydrochloride tablets 1 mg twice a day were compared to prochlorperazine 10 mg twice a day derived from a historical control. At 24 hours, there was no statistically significant difference in efficacy between the two granisetron hydrochloride tablet regimens. Both regimens were statistically superior to the prochlorperazine control regimen (see Table 3 ).
Table 3 Prevention of Nausea and Vomiting 24 Hours Post-Chemotherapy 1 Percentages of Patients Efficacy Measures Granisetron Hydrochloride Tablets 1 mg twice a day (n = 354) % Granisetron Hydrochloride Tablets 2 mg once a day (n = 343) % Prochlorperazine 2 10 mg twice daily (n=111) % Complete Response 3 69* 64* 41 No Vomiting 82* 77* 48 No Nausea 51* 53* 35 Total Control 4 51* 50* 33 1 Moderately emetogenic chemotherapeutic agents included cisplatin (20 mg/m 2 to 50 mg/m 2 ), oral and intravenous cyclophosphamide, carboplatin, dacarbazine, doxorubicin.
2 Historical control from a previous double-blind granisetron hydrochloride trial. 3 No vomiting, no moderate or severe nausea, no rescue medication. 4 No vomiting, no nausea, no rescue medication. *Statistically significant (P<0.05) vs. prochlorperazine historical control.
Results from a granisetron hydrochloride tablets 2 mg daily alone treatment arm in a third double-blind, randomized trial, were compared to prochlorperazine (PCPZ), 10 mg twice a day, derived from a historical control. The 24 hour results for granisetron hydrochloride tablets 2 mg daily were statistically superior to PCPZ for all efficacy parameters: complete response (58%), no vomiting (79%), no nausea (51%), total control (49%). The PCPZ rates are shown in Table 3 .
Cisplatin-Based Chemotherapy The first double-blind trial compared granisetron hydrochloride tablets 1 mg twice a day, relative to placebo (historical control), in 119 cancer patients receiving high-dose cisplatin (mean dose 80 mg/m 2 ). At 24 hours, granisetron hydrochloride tablets 1 mg twice a day was significantly (P<0.001) superior to placebo (historical control) in all efficacy parameters: complete response (52%), no vomiting (56%) and no nausea (45%). The placebo rates were 7%, 14%, and 7%, respectively, for the three efficacy parameters.
Results from a granisetron hydrochloride tablets 2 mg once a day alone treatment arm in a second double-blind, randomized trial, were compared to both granisetron hydrochloride tablets 1 mg twice a day and placebo historical cont… [Excerpted — this section continues on DailyMed.]
📄 Carcinogenesis, Mutagenesis, Impairment of Fertility ▾
Carcinogenesis, Mutagenesis, Impairment of Fertility In a 24 month carcinogenicity study, rats were treated orally with granisetron 1, 5 or 50 mg/kg/day (6, 30 or 300 mg/m 2 /day). The 50 mg/kg/day dose was reduced to 25 mg/kg/day (150 mg/m 2 /day) during week 59 due to toxicity. For a 50 kg person of average height (1.46 m 2 body surface area), these doses represent 4, 20, and 101 times the recommended clinical dose (1.48 mg/m 2 , oral) on a body surface area basis.
There was a statistically significant increase in the incidence of hepatocellular carcinomas and adenomas in males treated with 5 mg/kg/day (30 mg/m 2 /day, 20 times the recommended human dose based on body surface area) and above, and in females treated with 25 mg/kg/day (150 mg/m 2 /day, 101 times the recommended human dose based on body surface area). No increase in liver tumors was observed at a dose of 1 mg/kg/day (6 mg/m 2 /day, 4 times the recommended human dose based on body surface area) in males and 5 mg/kg/day (30 mg/m 2 /day, 20 times the recommended human dose based on body surface area) in females.
In a 12 month oral toxicity study, treatment with granisetron 100 mg/kg/day (600 mg/m 2 /day, 405 times the recommended human dose based on body surface area) produced hepatocellular adenomas in male and female rats while no such tumors were found in the control rats. A 24 month mouse carcinogenicity study of granisetron did not show a statistically significant increase in tumor incidence, but the study was not conclusive. Because of the tumor findings in rat studies, granisetron hydrochloride should be prescribed only at the dose and for the indication recommended (see INDICATIONS AND USAGE , and DOSAGE AND ADMINISTRATION ).
Granisetron was not mutagenic in in vitro Ames test and mouse lymphoma cell forward mutation assay, and in vivo mouse micronucleus test and in vitro and ex vivo rat hepatocyte UDS assays. It, however, produced a significant increase in UDS in HeLa cells in vitro and a significant increased incidence of cells with polyploidy in an in vitro human lymphocyte chromosomal aberration test. Granisetron at oral doses up to 100 mg/kg/day (600 mg/m 2 /day, 405 times the recommended human dose based on body surface area) was found to have no effect on fertility and reproductive performance of male and female rats.
📄 Package Label / Principal Display Panel ▾
PACKAGE LABEL.PRINCIPAL DISPLAY PANEL NDC 69452-350-92 Granisetron Hydrochloride Tablets, USP 1 mg* per tablet * Each tablet contains 1.12 mg granisetron hydrochloride USP equivalent to granisetron, 1 mg. Intended For Institutional Use Only. Rx only 20 (2 x 10) Unit Dose Tablets BIONPHARMA carton