Granisetron Hydrochloride 1 mg/mL Injection
🆔 Identity & classification
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🏷️ RxNorm drug class
This medicine belongs to the Serotonin-3 Receptor Antagonist class.
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🏭 Manufacturer & labeler
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🩺 Clinical
- 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...
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🧪 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.
💡 Tap an ingredient (hover on desktop) to see what it is and why it’s used.
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2 mg / 1 mL
UNII XF417D3PSL
Anhydrous citric acid is a sour, crystalline powder derived from citric acid with water removed. In medicines, it acts as a buffer to control pH, adds tartness to improve taste, and helps tablets disintegrate.
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10 mg / 1 mL
UNII LKG8494WBH
Benzyl alcohol is a clear liquid used as a preservative and solvent in medicines. It helps prevent bacterial and fungal growth and dissolves other ingredients to create uniform liquid formulations.
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UNII QTT17582CB
A strong acid used to adjust and maintain the proper pH level in liquid medicines, ensuring stability and preventing breakdown of active ingredients.
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9 mg / 1 mL
UNII 451W47IQ8X
Sodium chloride is common table salt. It's used in medicines as a buffer to maintain proper pH, as a filler to add bulk, or to adjust the osmotic balance in liquid formulations.
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UNII 55X04QC32I
A strong alkaline chemical used to adjust and maintain the pH balance of liquid medicines. It helps keep the medicine stable and ensures it stays effective during storage.
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UNII 059QF0KO0R
Water is a liquid solvent that dissolves and mixes ingredients together in liquid medicines, syrups, and injections. It helps distribute the active drug evenly throughout the product.
6 inactive ingredients listed in the exact product block matched to this NDC.
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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.Inactive ingredient FAQ
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💲 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 each | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | Not in the retail survey — common for institutional, discontinued, or low-volume packs. | |
| Medicaid paysCMS SDUD · 12 mo | $8.63 | $43.13 / 5 vials |
| Medicare drug plans payPart D · quarterly | No Part D plan price is available for this NDC in our data. | |
| Medicare Part B allowsASP · J1626 | $0.199 / J1626 unit | — |
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🧾 Billing & reimbursement
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🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Granisetron Hydrochloride 1 mg/mLthis 00143-9745-05 | Hikma | 5 vials | — | AP | FDA listed | — |
| Granisetron Hydrochloride 4 mg/4mL 55150-0176-04 | Eugia | 1 vial | — | — | FDA listed | — |
| Granisetron Hydrochloride 1 mg/mL 67457-0864-04 | Mylan | 1 vial | — | AP | FDA listed | — |
| Granisetron Hydrochloride 1 mg/mL 00143-9744-10 | Hikma | 10 vials | — | AP | FDA listed | — |
| Granisetron 1 mg/mL 63323-0318-01 | Fresenius | 1 vial | — | AP | FDA listed | — |
| Granisetron Hydrochloride 1 mg/mL 55150-0175-01 | Eugia | 1 vial | — | — | FDA listed | — |
| Granisetron Hydrochloride 1 mg/mL 67457-0863-01 | Mylan | 1 vial | — | AP | FDA listed | — |
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⏳ Availability & generic status
This product is an FDA-approved generic. Other versions of the same drug are listed under Therapeutic equivalents, least expensive first.
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🗺️ Medicaid utilization & spend
💊 Medicaid utilization by pack size
🔬 Reported adverse events (FAERS)
Top reported reactions
Age at onset
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Serious outcomes
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📦 Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Status |
|---|---|---|---|
| 00143-9745-05 You're viewing this | 5 VIAL, MULTI-DOSE in 1 CARTON (0143-9745-05) / 4 mL in 1 VIAL, MULTI-DOSE (0143-9745-01) | 2009-12-23 | Active |
| 00143-9745-10 | 10 VIAL, MULTI-DOSE in 1 CARTON (0143-9745-10) / 4 mL in 1 VIAL, MULTI-DOSE (0143-9745-01) | 2009-12-23 | Active |
In Medicaid, this is the most-dispensed pack of this product — about 100% of fills over the last four reported quarters. See all packs ↓
Pack size FAQ
What quantity is in NDC 00143-9745-05?
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🧭 About this NDC listing & data coverage
What data is (and isn’t) available for this NDC — tap to expand
| NDC identity (package / product / labeler codes) | ✓ Available |
| Labeler | ✓ Available |
| Product & package description | ✓ Available |
| Marketing category & status | ✓ Available |
| Active ingredient / dosage form / route | ✓ Available |
| FDA label (SPL via DailyMed) | ✓ Available |
| Package photos | ✓ Available |
| Inactive ingredients (structured) | ✓ Available |
| NADAC pharmacy acquisition price (CMS) | — Not published for this NDC CMS publishes NADAC only for NDCs reported in its retail-pharmacy survey. |
| Orange Book / therapeutic-equivalence data | ✓ Available |
| HCPCS J-code billing crosswalk | ✓ Available |
| Medicaid utilization (CMS SDUD) | ✓ Available |
Questions about this listing
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📄 Full prescribing information FDA SPL
🎯 Indications and Usage ▾
1 INDICATIONS AND USAGE Granisetron Hydrochloride Injection, USP is a serotonin-3 (5-HT 3 ) receptor antagonist indicated for: The prevention of nausea and/or vomiting associated with initial and repeat courses of emetogenic cancer therapy, including high-dose cisplatin. Granisetron Hydrochloride Injection, USP is a serotonin-3 (5-HT 3 ) receptor antagonist indicated for: Prevention of nausea and/or vomiting associated with initial and repeat courses of emetogenic cancer therapy, including high-dose cisplatin. ( 1 )
⏱️ Dosage and Administration ▾
2 DOSAGE AND ADMINISTRATION Prevention of chemotherapy-induced nausea and vomiting ( 2.1 ) : Recommended dosage is 10 mcg/kg intravenously within 30 minutes before initiation of chemotherapy Pediatric patients (2 to 16 years): Recommended dosage is 10 mcg/kg
2.1Prevention of Chemotherapy-Induced Nausea and Vomiting Adult Patients The recommended dosage for Granisetron Hydrochloride Injection is 10 mcg/kg administered intravenously within 30 minutes before initiation of chemotherapy, and only on the day(s) chemotherapy is given. Infusion Preparation Granisetron Hydrochloride Injection may be administered intravenously either undiluted over 30 seconds or diluted with 0.9% Sodium Chloride or 5% Dextrose and infused over 5 minutes. Stability Intravenous infusion of Granisetron Hydrochloride Injection should be prepared at the time of administration.
However, Granisetron Hydrochloride Injection has been shown to be stable for at least 24 hours when diluted in 0.9% Sodium Chloride or 5% Dextrose and stored at room temperature under normal lighting conditions. As a general precaution, Granisetron Hydrochloride Injection should not be mixed in solution with other drugs. Parenteral drug products should be inspected visually for particulate matter and discoloration before administration whenever solution and container permit.
Pediatric Patients The recommended dose in pediatric patients 2 to 16 years of age is 10 mcg/kg [see Clinical Studies ( 14 )] . Pediatric patients under 2 years of age have not been studied.
💊 Dosage Forms and Strengths ▾
3 DOSAGE FORMS AND STRENGTHS Single Dose Vials for Injection: 1 mg/mL Multiple Dose Vials for Injection: 4 mg/4 mL (1 mg/mL) Injection 1 mg/mL (free base). ( 3 )
⛔ Contraindications ▾
4 CONTRAINDICATIONS Granisetron Hydrochloride Injection is contraindicated in patients with known hypersensitivity (e.g. anaphylaxis, shortness of breath, hypotension, urticaria) to the drug or to any of its components. Hypersensitivity to granisetron or to any of its components. ( 4 )
⚠️ Warnings and Cautions ▾
5 WARNINGS AND PRECAUTIONS Granisetron hydrochloride does not stimulate gastric or intestinal peristalsis and should not be used instead of nasogastric suction. ( 5.1 ) QT prolongation has been reported with granisetron hydrochloride. Use with caution in patients with pre-existing arrhythmias or cardiac conduction disorders.
( 5.2 ) Hypersensitivity reactions, such as anaphylaxis, shortness of breath, hypotension, and urticaria, may occur in patients with known hypersensitivity to other selective 5-HT 3 receptor antagonists. ( 5.3 ) Contains benzyl alcohol. ( 5.4 ) Serotonin syndrome has been reported with granisetron products, alone but particularly with concomitant use of serotonergic drugs.
( 5.5 )
5.1Gastric or Intestinal Peristalsis 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.
5.2Cardiovascular Events 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.
5.3Hypersensitivity Reactions Hypersensitivity reactions (e.g. anaphylaxis, shortness of breath, hypotension, urticaria) may occur in patients who have exhibited hypersensitivity to other selective 5-HT 3 receptor antagonists
5.4Benzyl Alcohol Granisetron Hydrochloride Injection 1 mg/mL contains benzyl alcohol. Benzyl alcohol, a component of Granisetron Hydrochloride Injection 1 mg/mL, has been associated with serious adverse reactions and death, particularly in neonates. The “gasping syndrome,” characterized by central nervous system depression, metabolic acidosis, gasping respirations, and high levels of benzyl alcohol and metabolites in blood and urine, has been associated with benzyl alcohol dosages >99 mg/kg/day in neonates and low birth-weight neonates.
Additional symptoms may include gradual neurological deterioration, seizures, intracranial hemorrhage, hematologic abnormalities, skin breakdown, hepatic and renal failure, hypotension, bradycardia, and cardiovascular collapse. Although normal therapeutic doses of this product deliver amounts of benzyl alcohol that are substantially lower than those reported in association with the “gasping syndrome,” the minimum amount of benzyl alcohol at which toxicity may occur is not known. Premature and low birth-weight infants, as well as patients receiving high dosages, may be more likely to develop toxicity.
Practitioners administering this and other medications containing benzyl alcohol should consider the combined daily metabolic load of benzyl alcohol from all sources.
5.5Serotonin 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…
🤒 Adverse Reactions ▾
6 ADVERSE REACTIONS QT prolongation has been reported with granisetron hydrochloride [see Warnings and Precautions ( 5.2 ) and Drug Interactions ( 7 )] . Most common adverse reactions: Chemotherapy-induced nausea and vomiting (≥3%): Headache, and constipation ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Hikma Pharmaceuticals USA Inc. at 1-877-845-0689 or FDA at 1-800-FDA-1088 or www . fda.gov/medwatch .
6.1Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in patients. Chemotherapy-Induced Nausea and Vomiting The following have been reported during controlled clinical trials or in the routine management of patients. The percentage figures are based on clinical trial experience only.
Table 1 gives the comparative frequencies of the two most commonly reported adverse reactions (≥3%) in patients receiving Granisetron Hydrochloride Injection, in single-day chemotherapy trials. These patients received chemotherapy, primarily cisplatin, and intravenous fluids during the 24-hour period following Granisetron Hydrochloride Injection administration. Reactions were generally recorded over seven days post-Granisetron Hydrochloride Injection administration.
Table 1. Principal Adverse Reactions in Clinical Trials — Single-Day Chemotherapy Percent of Patients With Reaction Granisetron Hydrochloride Injection 40 mcg/kg (n=1268) Comparator Metoclopramide/dexamethasone and phenothiazines/dexamethasone. (n=422) Headache 14% 6% Constipation 3% 3% Additional adverse events reported in clinical trials were asthenia, somnolence and diarrhea.
In over 3,000 patients receiving Granisetron Hydrochloride Injection (2 to 160 mcg/kg) in single-day and multiple-day clinical trials with emetogenic cancer therapies, adverse events, other than those adverse reactions listed in Table 1, were observed; attribution of many of these events to granisetron hydrochloride is uncertain. Hepatic: In comparative trials, mainly with cisplatin regimens, elevations of AST and ALT (>2 times the upper limit of normal) following administration of Granisetron Hydrochloride Injection occurred in 2.8% and 3.3% of patients, respectively.
These frequencies were not significantly different from those seen with comparators (AST: 2.1%; ALT: 2.4%). Cardiovascular: Hypertension (2%); hypotension, arrhythmias such as sinus bradycardia, atrial fibrillation, varying degrees of A-V block, ventricular ectopy including non-sustained tachycardia, and ECG abnormalities have been observed rarely. Central Nervous System: Agitation, anxiety, CNS stimulation and insomnia were seen in less than 2% of patients.
Extrapyramidal syndrome occurred rarely and only in the presence of other drugs associated with this syndrome. Hypersensitivity: Rare cases of hypersensitivity reactions, sometimes severe (eg, anaphylaxis, shortness of breath, hypotension, urticaria) have been reported. Other: Fever (3%), taste disorder (2%), skin rashes (1%).
In multiple-day comparative studies, fever occurred more frequently with Granisetron Hydrochloride Injection (8.6%) than with comparative drugs (3.4%, P<0.014), which usually included dexamethasone.
6.2Postmarketing Experience The following adverse reactions have been identified during post approval use of granisetron hydrochloride. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to granisetron hydrochloride exposure. QT prolongation has been reported with granisetron hydrochloride [see Warnings and Precautions ( 5.2 ) and Drug Interactions ( 7 )] .
🔄 Drug Interactions ▾
7 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 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 and Precautions ( 5.5 )]. Granisetron Hydrochloride Injection, USP has been administered safely with benzodiazepines, neuroleptics, and anti-ulcer medications. ( 7 ) Does not appear to interact with emetogenic cancer chemotherapies.
( 7 ) Inducers or inhibitors of CYP450 enzymes may change the clearance and therefore the half-life of granisetron. ( 7 ) Coadministration of granisetron hydrochloride with drugs known to prolong the QT interval and/or are arrhythmogenic may result in clinical consequences. ( 7 )
👥 Use in Specific Populations ▾
8 USE IN SPECIFIC POPULATIONS Pregnancy: Use only if clearly needed. ( 8.1 ) Nursing mothers: Caution should be exercised when administered to a nursing woman. ( 8.3 ) Pediatric use: Safety and efficacy in pediatric patients have not been established for use in postoperative nausea and vomiting. ( 8.4 ) Geriatric use: No differences in responses between the elderly and younger patients were observed in reported clinical experience. ( 8.5 )
8.1Pregnancy Teratogenic Effects Pregnancy Category B Reproduction studies have been performed in pregnant rats at intravenous doses up to 9 mg/kg/day (54 mg/m 2 /day, 146 times the recommended human dose based on body surface area) and pregnant rabbits at intravenous doses up to 3 mg/kg/day (35.4 mg/m 2 /day, 96 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. Benzyl alcohol may cross the placenta. Granisetron Hydrochloride Injection 1 mg/mL is preserved with benzyl alcohol and should be used in pregnancy only if the benefit outweighs the potential risk.
8.3Nursing 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 Injection is administered to a nursing woman.
8.4Pediatric Use Benzyl alcohol, a component of Granisetron Hydrochloride Injection 1 mg/mL, has been associated with serious adverse reactions and death, particularly in neonates [see Warnings and Precautions ( 5.4 )] . Chemotherapy-Induced Nausea and Vomiting [See Dosage and Administration ( 2 )] for use in chemotherapy-induced nausea and vomiting in pediatric patients 2 to 16 years of age. Safety and effectiveness in pediatric patients under 2 years of age have not been established.
Postoperative Nausea and Vomiting Safety and efficacy have not been established in pediatric patients for the prevention of postoperative nausea and vomiting (PONV). Granisetron has been evaluated in a pediatric patient clinical trial for use in the prevention of PONV. Due to the lack of efficacy and the QT prolongation observed in this trial, use of granisetron for the prevention of PONV in children is not recommended.
The trial was a prospective, multicenter, randomized, double-blind, parallel-group trial that evaluated 157 children aged 2 to 16 years who were undergoing elective surgery for tonsillectomy or adenotonsillectomy. The purpose of the trial was to assess two dose levels (20 mcg/kg and 40 mcg/kg) of intravenous granisetron in the prevention of PONV. There was no active comparator or placebo.
The primary endpoint was total control of nausea and vomiting (defined as no nausea, vomiting/retching, or use of rescue medication) in the 24 hours following surgery. Efficacy was not established due to lack of a dose response. The trial also included standard 12 lead ECGs performed pre-dose and after the induction of anesthesia.
ECGs were repeated at the end of surgery after the administration of granisetron and just prior to reversal of anesthesia. QT prolongation was seen at both dose levels. Five patients in this trial experienced an increase of ≥ 60 msec in QTcF.
In addition, there were two patients whose QTcF was ≥ 500 msec. Interpretation of the QTcF prolongation was confounded by multiple factors, including the use of concomitant medication and the lack of either a placebo or active control. A thorough QT trial in adults has not been performed.
Other adverse events that occurred in the study included: vomiting (5 to 8%), post-procedural hemorrhage (3 to 5%), and dehydration (0 to 5%). Pediatric patients under 2 years of age have not been studied.
8.5 Geriatric Use During chemotherapy clinical…
🤰 Pregnancy ▾
8.1Pregnancy Teratogenic Effects Pregnancy Category B Reproduction studies have been performed in pregnant rats at intravenous doses up to 9 mg/kg/day (54 mg/m 2 /day, 146 times the recommended human dose based on body surface area) and pregnant rabbits at intravenous doses up to 3 mg/kg/day (35.4 mg/m 2 /day, 96 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. Benzyl alcohol may cross the placenta. Granisetron Hydrochloride Injection 1 mg/mL is preserved with benzyl alcohol and should be used in pregnancy only if the benefit outweighs the potential risk.
🧒 Pediatric Use ▾
8.4Pediatric Use Benzyl alcohol, a component of Granisetron Hydrochloride Injection 1 mg/mL, has been associated with serious adverse reactions and death, particularly in neonates [see Warnings and Precautions ( 5.4 )] . Chemotherapy-Induced Nausea and Vomiting [See Dosage and Administration ( 2 )] for use in chemotherapy-induced nausea and vomiting in pediatric patients 2 to 16 years of age. Safety and effectiveness in pediatric patients under 2 years of age have not been established.
Postoperative Nausea and Vomiting Safety and efficacy have not been established in pediatric patients for the prevention of postoperative nausea and vomiting (PONV). Granisetron has been evaluated in a pediatric patient clinical trial for use in the prevention of PONV. Due to the lack of efficacy and the QT prolongation observed in this trial, use of granisetron for the prevention of PONV in children is not recommended.
The trial was a prospective, multicenter, randomized, double-blind, parallel-group trial that evaluated 157 children aged 2 to 16 years who were undergoing elective surgery for tonsillectomy or adenotonsillectomy. The purpose of the trial was to assess two dose levels (20 mcg/kg and 40 mcg/kg) of intravenous granisetron in the prevention of PONV. There was no active comparator or placebo.
The primary endpoint was total control of nausea and vomiting (defined as no nausea, vomiting/retching, or use of rescue medication) in the 24 hours following surgery. Efficacy was not established due to lack of a dose response. The trial also included standard 12 lead ECGs performed pre-dose and after the induction of anesthesia.
ECGs were repeated at the end of surgery after the administration of granisetron and just prior to reversal of anesthesia. QT prolongation was seen at both dose levels. Five patients in this trial experienced an increase of ≥ 60 msec in QTcF.
In addition, there were two patients whose QTcF was ≥ 500 msec. Interpretation of the QTcF prolongation was confounded by multiple factors, including the use of concomitant medication and the lack of either a placebo or active control. A thorough QT trial in adults has not been performed.
Other adverse events that occurred in the study included: vomiting (5 to 8%), post-procedural hemorrhage (3 to 5%), and dehydration (0 to 5%). Pediatric patients under 2 years of age have not been studied.
🧓 Geriatric Use ▾
8.5Geriatric Use During chemotherapy clinical trials, 713 patients 65 years of age or older received Granisetron Hydrochloride Injection. The safety and effectiveness were similar in patients of various ages.
🆘 Overdosage ▾
10 OVERDOSAGE There is no specific antidote for Granisetron Hydrochloride Injection 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 ▾
12 CLINICAL PHARMACOLOGY
12.1Mechanism of Action 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 alpha 1- , alpha 2- or beta-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-induced vomiting, mucosal enterochromaffin cells release serotonin, which stimulates 5-HT 3 receptors.
This evokes vagal afferent discharge and may induce 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. Granisetron Hydrochloride Injection exhibited no effect on oro-cecal transit time in normal volunteers given a single intravenous infusion of 50 mcg/kg or 200 mcg/kg.
Single and multiple oral doses slowed colonic transit in normal volunteers.
12.3Pharmacokinetics Chemotherapy-Induced Nausea and Vomiting In adult cancer patients undergoing chemotherapy and in volunteers, mean pharmacokinetic data obtained from an infusion of a single 40 mcg/kg dose of Granisetron Hydrochloride Injection are shown in Table 2. Table 2. Pharmacokinetic Parameters in Adult Cancer Patients Undergoing Chemotherapy and in Volunteers, Following a Single Intravenous 40 mcg/kg Dose of Granisetron Hydrochloride Injection Peak Plasma Concentration (ng/mL) Terminal Phase Plasma Half-Life (h) Total Clearance (L/h/kg) Volume of Distribution (L/kg) Cancer Patients Mean 63.8 5-minute infusion.
8.950.38
3.07Range 18.0 to 176 0.90 to 31.1 0.14 to 1.54 0.85 to
10.4Volunteers 21 to 42 years Mean 64.3 3-minute infusion. 4.91 0.79
3.04Range 11.2 to 182 0.88 to 15.2 0.20 to 2.56 1.68 to 6.13 65 to 81 years Mean 57.0 7.69 0.44
3.97Range 14.6 to 153 2.65 to 17.7 0.17 to 1.06 1.75 to
7.01Distribution 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 12% of the administered dose is eliminated unchanged in the urine in 48 hours.
The remainder of the dose is excreted as metabolites, 49% in the urine, and 34% in the feces. Subpopulations Gender There was high inter- and intra-subject variability noted in these studies. No difference in mean AUC was found between males and females, although males had a higher Cmax generally.
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 patients (see Table 2). 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 incr…
🧬 Mechanism of Action ▾
12.1Mechanism of Action 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 alpha 1- , alpha 2- or beta-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-induced vomiting, mucosal enterochromaffin cells release serotonin, which stimulates 5-HT 3 receptors.
This evokes vagal afferent discharge and may induce 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. Granisetron Hydrochloride Injection exhibited no effect on oro-cecal transit time in normal volunteers given a single intravenous infusion of 50 mcg/kg or 200 mcg/kg.
Single and multiple oral doses slowed colonic transit in normal volunteers.
📦 How Supplied / Storage and Handling ▾
16 HOW SUPPLIED/STORAGE AND HANDLING Granisetron Hydrochloride Injection, USP 1 mg/mL (free base), is supplied in 1 mL Single Dose Vials and 4 mL Multiple Dose Vials. CONTAINS BENZYL ALCOHOL. NDC 0143-9744-10 (Carton of 10 x 1 mL Single Dose Vials) NDC 0143-9745-10 (Carton of 10 x 4 mL Multiple Dose Vials) NDC 0143-9745-05 (Carton of 5 x 4 mL Multiple Dose Vials) Store single dose vials and multiple dose vials at 20° to 25°C (68° to 77°F); excursions permitted to 15° to 30°C (59° to 86°F). [See USP Controlled Room Temperature] Discard unused portion for the single dose vials.
Once the multiple dose vial is penetrated, its contents should be used within 30 days. Do not freeze. Protect from light.
Retain in carton until time of use.
📋 Description ▾
11 DESCRIPTION Granisetron Hydrochloride Injection, USP is a serotonin-3 (5-HT 3 ) receptor antagonist. 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 C18H24N4O•HCl, while its chemical structure is: Granisetron hydrochloride is a white to off-white solid that is readily soluble in water and normal saline at 20°C.
Granisetron Hydrochloride Injection, USP is a clear, colorless, sterile, nonpyrogenic, aqueous solution for intravenous administration. Granisetron Hydrochloride Injection, USP 1 mg/mL is available in 1 mL single dose and 4 mL multiple dose vials. 1 mg/mL: Each mL contains 1.12 mg granisetron hydrochloride equivalent to granisetron, 1 mg; sodium chloride, 9 mg; citric acid anhydrous, 2 mg; and benzyl alcohol, 10 mg, as a preservative.
The solution’s pH ranges from 4.0 to 6.0; pH adjusted with sodium hydroxide/hydrochloric acid. chemical structure
💬 Information for Patients ▾
17 PATIENT COUNSELING INFORMATION Patients should be informed that the most common adverse reactions for the indication of chemotherapy induced nausea and vomiting are headache and constipation (see Table 1). Patients should be advised of the risk of allergic reactions if they have a prior allergic reaction to a class of antiemetics known as 5-HT 3 receptor antagonists. Electrocardiogram changes (QT prolongation) have been reported with the use of granisetron hydrochloide.
Patients should be cautioned about the use of this drug if they have heart problems or take medications for heart problems. Patients should be informed that Granisetron Hydrochloride Injection (1 mg/mL) contains benzyl alcohol and may cause serious side effects in newborns. Advise patients of the possibility of serotonin syndrome with concomitant use of granisetron and another serotonergic agent such as medications to treat depression and migraines.
Advise patients to seek immediate medical attention if the following symptoms occur: changes in mental status, autonomic instability, neuromuscular symptoms with or without gastrointestinal symptoms. Manufactured by: HIKMA FARMACÊUTICA (PORTUGAL), S.A. Estrada do Rio da Mó, nº 8, 8A e 8B - Fervença, 2705 – 906 Terrugem SNT PORTUGAL Distributed by: Hikma Pharmaceuticals USA Inc.
Berkeley Heights, NJ 07922 Revised: August 2020 PIN225-WES/7