Granisetron HCl is an antiemetic drug, given for prevention of chemotherapy-induced nausea and for pre- and post-surgical nausea and vomiting. The drug is administered by intravenous (IV) injection, followed by oral administration. The IV administration is inconvenient, and oral dosing is often not effective in maintaining the desired constant drug levels in the bloodstream. A Transdermal delivery of Granisetron can replace the IV and subsequent oral administration.
Granisetron is another 5HT3 antagonist (dolasetron, ondansetron and tropisetron are already available). It is approved for the prevention and treatment of nausea and vomiting due to cytotoxic drugs or surgery. Although it is approved for prevention, there are limited data to support the use of granisetron in the treatment of nausea and vomiting due to radiotherapy. Granisetron HCl falls within a class of small, very hydrophilic drug-molecules that cannot be delivered efficiently using existing passive transdermal delivery methods. Using Granisetron, TransPharma was able to demonstrate excellent results related to the three primary parameters: sustained release, constant blood drug levels and ease-of-use.
Serotonin antagonists may be no more effective than a regimen of metoclopramide and dexamethasone, but they are usually easier to give. Practitioners will now have to decide whether to prescribe dolasetron, ondansetron, tropisetron or granisetron. The drugs appear to be similar in effectiveness, so the choice of treatment may be influenced by its price.
This medicine is used to prevent or treat nausea and vomiting. The nausea and vomiting can be caused by chemotherapy, radiation therapy, or from surgery. Granisetron blocks chemicals in the body that cause the problem. It does this in the stomach and in the brain. Headache is the most frequent adverse reaction, but patients may also complain of constipation or sleepiness. Granisetron promotes liver cancer in rats, but the clinical significance is uncertain. Altered liver function has been reported in humans.
Action/Kinetics: Selective 5-HT3 (serotonin) receptor antagonist with little or no affinity for other 5-HT, beta-adrenergic, dopamine, or histamine receptors. During chemotherapy-induced vomiting, mucosal enterochromaffin cells release serotonin, which stimulates 5-HT3 receptors. The stimulation of 5-HT3 receptors by serotonin causes vagal discharge resulting in vomiting. Granisetron blocks serotonin stimulation and subsequent vomiting. In adult cancer clients undergoing chemotherapy, infusion of a single 40-mcg/kg dose over 5 min produced the following data. Peak plasma level: 63.8 ng/mL. Plasma t1/2, terminal: 8.95 hr. Metabolized in the liver with unchanged drug (12%) and metabolites excreted through both the urine and feces.
Uses: Prevention of N&V associated with initial and repeat cancer chemotherapy, including high-dose cisplatin. Prevention of N&V associated with radiation, including total body irradiation and fractionated abdominal radiation. Investigational: Acute N&V following surgery.
Molecular Formula: C18H24N4O•HCl
Molecular Weight: 348.89
CAS No.: 107007-99-8