KYTRIL (Granisteron)Chemotherapy-induced nausea and vomiting (CINV) and radiotherapyinduced nausea and vomiting (RINV)
Nausea and vomiting remain the most significant and debilitating side-effects of cytotoxic chemotherapy,
and also occurs in significant numbers of patients undergoing radiation therapy and after certain types of
surgery. These symptoms therefore represent a major therapeutic challenge in both cancer and
postoperative care and, if not adequately controlled by antiemetic treatment, can threaten the success of
the therapy as well as result in increased mortality, morbidity and healthcare costs.
Severe nausea and vomiting not only seriously affect patients quality of life, but can become so
intolerable that patients are unwilling to continue with potentially life-saving treatment. Furthermore,
patients suffering from nausea and vomiting can also experience:
▪ Physical damage – e.g. dehydration, electrolyte imbalances, malnutrition, fractures and lacerations of
the esophagus) to which the elderly and patients with comorbid conditions are particularly susceptible
▪ Significant impairment of normal daily functioning
▪ Reduced enjoyment of leisure activities
▪ Severe depression
Patient demographics can affect the nausea and vomiting risk in chemotherapy-induced nausea and
vomiting (CINV) and radiotherapy-induced nausea and vomiting (RINV), for example:
▪ Poor control with prior chemotherapy
▪ Female gender
▪ Younger age
▪ Low alcohol intake
▪ Motion sickness
Highly emetogenic chemotherapy induce nausea and vomiting in more than 70% of patients. The goal of
any antiemetic therapy is to prevent the occurrence of nausea and vomiting completely. The major
determinant of emetic risk in RINV is the treatment field. Other factors that affect the emetogenicity of
radiation therapy include the dose of radiotherapy administered per fraction and the pattern of
fractionation. Although radiotherapy is perceived as less emetogenic than chemotherapy, almost all
patients who receive total body irradiation (TBI) experience RINV and up to 50% of these still suffer from
nausea and vomiting despite being treated with prophylactic antiemetics.
KYTRIL FAQ
What are the indications for Kytril?
Kytril Injection is indicated for the prevention of:
▪ Nausea and vomiting associated with initial and repeat courses of emetogenic cancer therapy,
including high-dose cisplatin.
▪ Postoperative nausea and vomiting.
Kytril 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.
What are the pharmacologic features of Kytril?
Granisetron prevents nausea and vomiting by binding to 5-hydroxytrypatamine (5-HT3) receptors. From
animal studies, it is believed that binding of granisetron to 5-HT3 receptor sites located in the proximal gut
is the way in which the antiemetic effect is mediated. These sites play a pivotal role in producing the
emetic response to chemotherapeutic drugs.
When chemotherapy is administered, the cells in the gut are believed to release serotonin, which binds to
the 5-HT3 receptor sites in the proximal gut. These receptor sites are located on vagal afferent nerves,
which conduct messages from the gut to the brain. When these nerves are stimulated by serotonin
binding, they send impulses to the emetic center, triggering nausea and vomiting. By blocking the 5-HT3
receptor sites, granisetron prevents serotonin binding, thereby averting the emetic response.
How effective is Kytril?
Kytril Tablets and Injection effectively prevent nausea and vomiting in patients undergoing highly
emetogenic chemotherapy, as well as in patients receiving moderately emetogenic chemotherapy. A
single dose of Kytril Injection, Tablets or Oral Solution provide 24-hour protection against chemotherapy
induced nausea and vomiting, and maintains efficacy in patients receiving repeat cycles of
chemotherapy.
1. The efficacy of Kytril Injection has not been evaluated in patients receiving radiation or in children less
than 2 years of age receiving chemotherapy
2. The efficacy of Kytril Tablets have not been evaluated in children receiving chemotherapy or radiation
Is Kytril well tolerated?
Extensive research has shown that Kytril is well tolerated and can be safely used in a wide range of
patient types. Furthermore, the adverse events reported with Kytril are generally mild to moderate.
What were the most common adverse events in patients who received Kytril Tablets?
The most frequently reported adverse events were headache (21%), usually mild to moderate in severity;
constipation (18%); asthenia (14%); diarrhea (8%) and abdominal pain (6%). Adverse events were
determined in controlled clinical trials in which 978 patients received two 1-mg Kytril Tablets as a divided
dose for 1, 7 or 14 days. Adverse events (whether or not related to Kytril) were recorded for 7 days when
Kytril Tablets were given on a single day and for up to 28 days when Kytril Tablets were administered for
7 or 14 days.
What were the most common adverse events in patients who received Kytril Injection for CINV?
The most common adverse events reported by 1268 chemotherapy patients who received single doses
of Kytril injection in controlled clinical trials were headache (14%), asthenia (5%), somnolence (4%),
diarrhea (4%) and constipation (3%).
Are there any clinically significant cardiovascular risks associated with Kytril?
There are no clinically significant cardiovascular risks associated with Kytril. With Kytril Tablets,
hypertension, hypotension, angina pectoris, atrial fibrillation and syncope have been observed rarely.
With Kytril Injection, hypertension, 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.
What is the safety profile in elderly patients?
During clinical trials, 325 patients 65 years of age or older received Kytril Tablets. Efficacy and safety
were maintained with increasing age.
What is the safety profile of Kytril in pediatric patients?
Although neither the tablet nor oral solution have been studied in pediatric patients, clinical trials of the
intravenous formulation indicate that granisetron is well tolerated by children 2 through 16 years of age
receiving chemotherapy. In children less than 2 years of age receiving chemotherapy, the safety and
efficacy of Kytril has not been evaluated. Kytril has not been evaluated in children receiving radiation
therapy.
Are there any contraindications to Kytril?
The only known contraindication to Kytril is hypersensitivity to the drug or any of its components.
How is Kytril dosed and administered?
Kytril Injection
For the treatment of CINV. The recommended dose of Kytril Injection is 10 mcg/kg and can be
administered in either of two ways: undiluted and infused over just 30 seconds or diluted and infused
over 5 minutes. With the 30-second infusion, Kytril Injection can be infused undiluted directly into the Ysite, anytime within 30 minutes before initiation of chemotherapy and only on the day(s) chemotherapy is
given. If administered as a 5-minute infusion, Kytril Injection should be diluted at the time of
administration in 0.9% Sodium Chloride or 5% Dextrose and infused anytime within 30 minutes prior to
chemotherapy, and only on the day(s) chemotherapy is given.
For the prevention and treatment of PONV. The recommended dose is 1mg, undiluted, administered
intravenously over 30 seconds, before induction of anesthesia or immediately before reversal of
anesthesia.
Kytril Tablets
For the treatment of CINV. The recommended adult dosage of Kytril Tablets is a single 2-mg dose (two
1-mg tablets) given anytime within 1 hour before chemotherapy. Kytril Tablets can also be administered
as a divided dose, with the first 1-mg tablet administered anytime within 1 hour before chemotherapy and
the second 1-mg tablet given 12 hours after the first. Either regimen is administered only on the day(s)
chemotherapy is given.
For the treatment of RINV. The recommended adult dosage is 2 mg once daily. Two 1 mg tablets taken
within 1 hour of radiation (total body irradiation or fractionated abdominal radiation.)
The most frequently reported clinical adverse events occurring in >5% of patients receiving Kytril were headache,
constipation, asthenia, diarrhea, abdominal pain*, dyspepsia*, pain†, anemia†, fever† and elevated hepatic
enzymes†. The use of Kytril in patients following abdominal surgery or in patients with chemotherapy induced
nausea and vomiting may mask progressive ileus and/or gastric distention.
*Associated with Kytril Tablets only. †Associated with Kytril Injection for postoperative nausea and vomiting only.