FDA

Granisetron Hydrochloride

Approved 9 Apr 2010InjectionInjectable

The FDA lists this product in 56 strengths and forms.

Indications

Granisetron hydrochloride injection 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.
The prevention and treatment of postoperative nausea and vomiting in adults. As with other antiemetics, routine prophylaxis is not recommended in patients in whom there is little expectation that nausea and/or vomiting will occur postoperatively. In patients where nausea and/or vomiting must be avoided during the postoperative period, granisetron hydrochloride injection is recommended even where the incidence of postoperative nausea and/or vomiting is low. Granisetron hydrochloride injection is a serotonin-3 (5-HT3) 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 )
Prevention and treatment of postoperative nausea and vomiting in adults. ( 1 )

Contraindications

Granisetron hydrochloride injection is contraindicated in patients with known hypersensitivity (eg. 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 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 )
Serotonin syndrome has been reported with granisetron products, alone but particularly with concomitant use of serotonergic drugs. ( 5.4 )

Indications

Granisetron hydrochloride injection 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.
The prevention and treatment of postoperative nausea and vomiting in adults. As with other antiemetics, routine prophylaxis is not recommended in patients in whom there is little expectation that nausea and/or vomiting will occur postoperatively. In patients where nausea and/or vomiting must be avoided during the postoperative period, granisetron hydrochloride injection is recommended even where the incidence of postoperative nausea and/or vomiting is low. Granisetron hydrochloride injection is a serotonin-3 (5-HT3) 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 )
Prevention and treatment of postoperative nausea and vomiting in adults. ( 1 )

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 )
Serotonin syndrome has been reported with granisetron products, alone but particularly with concomitant use of serotonergic drugs. ( 5.4 )

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 norepinephrine reuptake Inhibitors (SNRIs) [see Warnings and Precautions (5.4) ].

Granisetron hydrochloride injection 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 )

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 )
Postoperative nausea and vomiting (≥2%): Pain, headache, fever, abdominal pain and hepatic enzymes increased ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Mylan Pharmaceuticals Inc.at 1-877-446-3679 (1-877-4-INFO-RX) 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 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 injection 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. Postoperative Nausea and Vomiting The adverse reactions listed in Table 2 were reported in ≥2% of adults receiving granisetron hydrochloride injection 1 mg during controlled clinical trials. Table 2 Adverse Reactions in Controlled Clinical Trials in Postoperative Nausea and Vomiting (Reported in ≥ 2% of Adults Receiving Granisetron Hydrochloride Injection 1 mg) Percent of Patients With Reaction Granisetron Hydrochloride Injection 1 mg (n=267) Placebo (n=266) Pain 10.1

8.3 Headache 8.6

7.1 Fever 7.9

4.5 Abdominal Pain 6 6 Hepatic Enzymes Increased 5.6

4.1 Dizziness 4.1

3.4 Diarrhea 3.4

1.1 Flatulence 3 3 Dyspepsia 3

1.9 Oliguria 2.2

1.5 Coughing 2.2

1.1 Additional adverse events reported in clinical trials were constipation, anemia, insomnia, bradycardia, leukocytosis, anxiety, hypotension, infection, hypertension, and urinary tract infection. In a clinical study conducted in Japan, the types of adverse events differed notably from those reported above in Table 2. The adverse events in the Japanese study that occurred in ≥2% of patients and were more frequent with granisetron hydrochloride 1 mg than with placebo were: fever (56% to 50%), sputum increased (2.7% to 1.7%), and dermatitis (2.7% to 0%).

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) ] .

Granisetron Hydrochloride

Indications

Contraindications

Warnings and precautions

Two medicines in one question?

Granisetron Hydrochloride

Indications

Contraindications

Warnings and precautions

Two medicines in one question?

5.1Gastric or Intestinal Peristalsis

5.2Cardiovascular Events

5.3Hypersensitivity Reactions

5.4Serotonin Syndrome

Interactions

Pregnancy and breastfeeding

8.1Pregnancy Teratogenic Effects Pregnancy Category B

Adverse reactions

6.1Clinical Trials Experience

6.2Postmarketing Experience

Composition

Strengths and forms

Official product information

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