Ondansetron-injection

Name: Ondansetron-injection

Uses

This medication is used alone or with other medications to prevent nausea and vomiting caused by cancer chemotherapy. It is also used to prevent and treat nausea and vomiting after surgery. It works by blocking one of the body's natural substances (serotonin) that causes vomiting.

How is ondansetron given?

Ondansetron is injected into a vein through an IV. A healthcare provider will give you this injection.

Ondansetron is usually given just before your surgery begins, or within 2 hours after surgery.

To prevent nausea and vomiting caused by chemotherapy, ondansetron is given 30 minutes before the start of chemotherapy. A second and third dose of ondansetron are sometimes given 4 hours and 8 hours after the first dose.

What should I avoid after receiving ondansetron?

This medicine may cause blurred vision and may impair your thinking or reactions. Be careful if you drive or do anything that requires you to be alert and able to see clearly.

Uses of Ondansetron Injection

  • It is used to treat or prevent upset stomach and throwing up.

What are some other side effects of Ondansetron Injection?

All drugs may cause side effects. However, many people have no side effects or only have minor side effects. Call your doctor or get medical help if any of these side effects or any other side effects bother you or do not go away:

  • Headache.
  • Feeling tired or weak.
  • Hard stools (constipation).
  • Loose stools (diarrhea).
  • Feeling sleepy.
  • Anxiety.
  • Irritation where the shot is given.

These are not all of the side effects that may occur. If you have questions about side effects, call your doctor. Call your doctor for medical advice about side effects.

You may report side effects to the FDA at 1-800-FDA-1088. You may also report side effects at http://www.fda.gov/medwatch.

If OVERDOSE is suspected

If you think there has been an overdose, call your poison control center or get medical care right away. Be ready to tell or show what was taken, how much, and when it happened.

How do I store and/or throw out Ondansetron Injection?

  • Most of the time, ondansetron injection will be given in a hospital or doctor's office. If stored at home, follow how to store as you were told by the doctor.
  • Keep all drugs in a safe place. Keep all drugs out of the reach of children and pets.
  • Check with your pharmacist about how to throw out unused drugs.

Warnings and Precautions

Hypersensitivity Reactions

Hypersensitivity reactions, including anaphylaxis and bronchospasm, have been reported in patients who have exhibited hypersensitivity to other selective 5-HT 3 receptor antagonists.

QT Prolongation

Ondansetron prolongs the QT interval in a dose-dependent manner [see Clinical Pharmacology (12.2)] . In addition, postmarketing cases of Torsade de Pointes have been reported in patients using ondansetron. Avoid Ondansetron Injection in patients with congenital long QT syndrome. ECG monitoring is recommended in patients with electrolyte abnormalities (e.g., hypokalemia or hypomagnesemia), congestive heart failure, bradyarrhythmias, or patients taking other medicinal products that lead to QT prolongation.

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 Ondansetron Injection 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 Ondansetron Injection and other serotonergic drugs. If symptoms of serotonin syndrome occur, discontinue Ondansetron Injection and initiate supportive treatment. Patients should be informed of the increased risk of serotonin syndrome, especially if Ondansetron Injection is used concomitantly with other serotonergic drugs [see Drug Interactions (7.5), Overdosage (10), Patient Counseling Information (17)] .

Masking of Progressive Ileus and Gastric Distension

The use of Ondansetron Injection in patients following abdominal surgery or in patients with chemotherapy-induced nausea and vomiting may mask a progressive ileus and gastric distention.

Effect on Peristalsis

Ondansetron Injection is not a drug that stimulates gastric or intestinal peristalsis. It should not be used instead of nasogastric suction.

Clinical Studies

The clinical efficacy of ondansetron hydrochloride, the active ingredient of Ondansetron Injection was assessed in clinical trials as described below.

Chemotherapy-induced Nausea and Vomiting

Adults

In a double-blind trial of three different dosing regimens of Ondansetron Injection 0.015 mg/kg, 0.15 mg/kg, and 0.30 mg/kg, each given three times during the course of cancer chemotherapy, the 0.15-mg/kg dosing regimen was more effective than the 0.015-mg/kg dosing regimen. The 0.30-mg/kg dosing regimen was not shown to be more effective than the 0.15-mg/kg dosing regimen.

Cisplatin-based Chemotherapy: In a double-blind trial in 28 patients,Ondansetron Injection (three 0.15-mg/kg doses) was significantly more effective than placebo in preventing nausea and vomiting induced by cisplatin-based chemotherapy. Therapeutic response was as shown in Table 7.

Table 7. Therapeutic Response in Prevention of Chemotherapy-induced Nausea and Vomiting in Single-day Cisplatin Therapy a in Adults

Ondansetron Injection (0.15 mg/kg x 3)

Placebo

P Value b

Number of patients

14

14

Treatment response

  • 0 Emetic episodes

2 (14%)

0 (0%)

  • 1-2 Emetic episodes

8 (57%)

0 (0%)

  • 3-5 Emetic episodes

2 (14%)

1 (7%)

  • More than 5 emetic episodes/rescued

2 (14%)

13 (93%)

0.001

Median number of emetic episodes

1.5

Undefined c

Median time to first emetic episode (h)

11.6

2.8

0.001

Median nausea scores (0-100) d

3

59

0.034

Global satisfaction with control of nausea and vomiting (0-100) e

96

10.5

0.009

a Chemotherapy was high dose (100 and 120 mg/m 2; Ondansetron Injection n = 6, placebo n = 5) or moderate dose (50 and 80 mg/m 2; Ondansetron Injection n = 8, placebo n = 9). Other chemotherapeutic agents included fluorouracil, doxorubicin, and cyclophosphamide. There was no difference between treatments in the types of chemotherapy that would account for differences in response.

b Efficacy based on "all-patients-treated" analysis.

c Median undefined since at least 50% of the patients were rescued or had more than five emetic episodes.

d Visual analog scale assessment of nausea: 0 = no nausea, 100 = nausea as bad as it can be.

e Visual analog scale assessment of satisfaction: 0 = not at all satisfied, 100 = totally satisfied.

Ondansetron Injection (0.15-mg/kg x 3 doses) was compared with metoclopramide (2 mg/kg x 6 doses) in a single-blind trial in 307 patients receiving cisplatin ≥ 100 mg/m 2 with or without other chemotherapeutic agents. Patients received the first dose of ondansetron or metoclopramide 30 minutes before cisplatin. Two additional ondansetron doses were administered 4 and 8 hours later, or five additional metoclopramide doses were administered 2, 4, 7, 10, and 13 hours later. Cisplatin was administered over a period of 3 hours or less. Episodes of vomiting and retching were tabulated over the period of 24 hours after cisplatin. The results of this trial are summarized in Table 8.

Table 8. Therapeutic Response in Prevention of Vomiting Induced by Cisplatin (≥ 100 mg/m 2) Single-day Therapy a in Adults

Ondansetron Injection

Metoclopramide

P Value

0.15 mg/kg x 3

2 mg/kg x 6

Number of patients in efficacy population

136

138

Treatment response

  • 0 Emetic episodes

54 (40%)

41 (30%)

  • 1-2 Emetic episodes

34 (25%)

30 (22%)

  • 3-5 Emetic episodes

19 (14%)

18 (13%)

  • More than 5 emetic episodes/rescued

29 (21%)

49 (36%)

Comparison of treatments with respect to

  • 0 Emetic episodes

54/136

41/138

0.083

  • More than 5 emetic episodes/rescued

29/136

49/138

0.009

Median number of emetic episodes

1

2

0.005

Median time to first emetic episode (h)

20.5

4.3

< 0.001

Global satisfaction with control of nausea and vomiting (0-100) b

85

63

0.001

Acute dystonic reactions

0

8

0.005

Akathisia

0

10

0.002

a In addition to cisplatin, 68% of patients received other chemotherapeutic agents, including cyclophosphamide, etoposide, and fluorouracil. There was no difference between treatments in the types of chemotherapy that would account for differences in response.

b Visual analog scale assessment: 0 = not at all satisfied, 100 = totally satisfied.

Cyclophosphamide-based Chemotherapy: In a double-blind, placebo-controlled trial of Ondansetron Injection (three 0.15-mg/kg doses) in 20 patients receiving cyclophosphamide (500 to 600 mg/m 2) chemotherapy, Ondansetron Injection was significantly more effective than placebo in preventing nausea and vomiting. The results are summarized in Table 9.

Table 9. Therapeutic Response in Prevention of Chemotherapy-induced Nausea and Vomiting in Single-day Cyclophosphamide Therapy a in Adults

Ondansetron Injection (0.15 mg/kg x 3)

Placebo

P Value b

Number of patients

10

10

Treatment response

  • 0 Emetic episodes

7 (70%)

0 (0%)

0.001

  • 1-2 Emetic episodes

0 (0%)

2 (20%)

  • 3-5 Emetic episodes

2 (20%)

4 (40%)

  • More than 5 emetic episodes/rescued

1 (10%)

4 (40%)

0.131

Median number of emetic episodes

0

4

0.008

Median time to first emetic episode (h)

Undefined c

8.79

Median nausea scores (0-100) d

0

60

0.001

Global satisfaction with control of nausea and vomiting (0-100) e

100

52

0.008

a Chemotherapy consisted of cyclophosphamide in all patients, plus other agents, including fluorouracil, doxorubicin, methotrexate, and vincristine. There was no difference between treatments in the type of chemotherapy that would account for differences in response.

b Efficacy based on "all-patients-treated" analysis.

c Median undefined since at least 50% of patients did not have any emetic episodes.

d Visual analog scale assessment of nausea: 0 = no nausea, 100 = nausea as bad as it can be.

e Visual analog scale assessment of satisfaction: 0 = not at all satisfied, 100 = totally satisfied.

Re-treatment: In uncontrolled trials, 127 patients receiving cisplatin (median dose, 100 mg/m 2) and ondansetron who had two or fewer emetic episodes were re-treated with ondansetron and chemotherapy, mainly cisplatin, for a total of 269 re-treatment courses (median: 2; range: 1 to 10). No emetic episodes occurred in 160 (59%), and two or fewer emetic episodes occurred in 217 (81%) re-treatment courses.

Pediatrics

Four open-label, noncomparative (one US, three foreign) trials have been performed with 209 pediatric cancer patients aged 4 to 18 years given a variety of cisplatin or noncisplatin regimens. In the three foreign trials, the initial dose of Ondansetron Injection ranged from 0.04 to 0.87 mg/kg for a total dose of 2.16 to 12 mg. This was followed by the oral administration of ondansetron ranging from 4 to 24 mg daily for 3 days. In the US trial, Ondansetron Injection was administered intravenously (only) in three doses of 0.15 mg/kg each for a total daily dose of 7.2 to 39 mg. In these trials, 58% of the 196 evaluable patients had a complete response (no emetic episodes) on Day 1. Thus, prevention of vomiting in these pediatric patients was essentially the same as for patients older than 18 years.

An open-label, multicenter, noncomparative trial has been performed in 75 pediatric cancer patients 6 to 48 months receiving at least one moderately or highly emetogenic chemotherapeutic agent. Fifty-seven percent (57%) were females; 67% were white, 18% were American Hispanic, and 15% were black patients. Ondansetron Injection was administered intravenously over 15 minutes in three doses of 0.15 mg/kg. The first dose was administered 30 minutes before the start of chemotherapy; the second and third doses were administered 4 and 8 hours after the first dose, respectively. Eighteen patients (25%) received routine prophylactic dexamethasone (i.e., not given as rescue). Of the 75 evaluable patients, 56% had a complete response (no emetic episodes) on Day 1. Thus, prevention of vomiting in these pediatric patients was comparable to the prevention of vomiting in patients aged 4 years and older.

Prevention of Postoperative Nausea and/or Vomiting

Adults

Adult surgical patients who received ondansetron immediately before the induction of general balanced anesthesia (barbiturate: thiopental, methohexital, or thiamylal; opioid: alfentanil or fentanyl; nitrous oxide; neuromuscular blockade: succinylcholine/curare and/or vecuronium or atracurium; and supplemental isoflurane) were evaluated in two double-blind US trials involving 554 patients. Ondansetron Injection (4 mg) intravenous given over 2 to 5 minutes was significantly more effective than placebo. The results of these trials are summarized in Table 10.

Table 10. Therapeutic Response in Prevention of Postoperative Nausea and Vomiting in Adult Patients

Ondansetron 4 mg Intravenous

Placebo

P Value

Study 1

Emetic episodes:

Number of patients

136

139

Treatment response over 24-h postoperative period

  • 0 Emetic episodes

103 (76%)

64 (46%)

< 0.001

  • 1 Emetic episode

13 (10%)

17 (12%)

  • More than 1 emetic episode/rescued

20 (15%)

58 (42%)

Nausea assessments:

Number of patients

134

136

No nausea over 24-h postoperative period

56 (42%)

39 (29%)

Study 2

Emetic episodes:

Number of patients

136

143

Treatment response over 24-h postoperative period

  • 0 Emetic episodes

85 (63%)

63 (44%)

0.002

  • 1 Emetic episode

16 (12%)

29 (20%)

  • More than 1 emetic episode/rescued

35 (26%)

51 (36%)

Nausea assessments:

Number of patients

125

133

No nausea over 24-h postoperative period

48 (38%)

42 (32%)


The populations in Table 10 consisted mainly of females undergoing laparoscopic procedures.

In a placebo-controlled trial conducted in 468 males undergoing outpatient procedures, a single 4-mg intravenous ondansetron dose prevented postoperative vomiting over a 24-hour period in 79% of males receiving drug compared with 63% of males receiving placebo ( P < 0.001)

Two other placebo-controlled trials were conducted in 2,792 patients undergoing major abdominal or gynecological surgeries to evaluate a single 4-mg or 8-mg intravenous ondansetron dose for prevention of postoperative nausea and vomiting over a 24-hour period. At the 4-mg dosage, 59% of patients receiving ondansetron versus 45% receiving placebo in the first trial ( P < 0.001) and 41% of patients receiving ondansetron versus 30% receiving placebo in the second trial ( P = 0.001) experienced no emetic episodes. No additional benefit was observed in patients who received intravenous ondansetron 8 mg compared with patients who received intravenous ondansetron 4 mg.

Pediatrics

Three double-blind, placebo-controlled trials have been performed (one US, two foreign) in 1,049 male and female patients (aged 2 to 12 years) undergoing general anesthesia with nitrous oxide. The surgical procedures included tonsillectomy with or without adenoidectomy, strabismus surgery, herniorrhaphy, and orchidopexy. Patients were randomized to either single intravenous doses of ondansetron (0.1 mg/kg for pediatric patients weighing 40 kg or less, 4 mg for pediatric patients weighing more than 40 kg) or placebo. Study drug was administered over at least 30 seconds, immediately prior to or following anesthesia induction. Ondansetron was significantly more effective than placebo in preventing nausea and vomiting. The results of these trials are summarized in Table 11.

Table 11. Therapeutic Response in Prevention of Postoperative Nausea and Vomiting in Pediatric Patients Aged 2 to 12 Years

Treatment Response Over 24 Hours

Ondansetron

n (%)

Placebo

n (%)

P Value

Study 1

Number of patients

205

210

0 Emetic episodes

140 (68%)

82 (39%)

≥ 0.001

Failure a

65 (32%)

128 (61%)

Study 2

Number of patients

112

110

0 Emetic episodes

68 (61%)

38 (35%)

≥ 0.001

Failure a

44 (39%)

72 (65%)

Study 3

Number of patients

206

206

0 Emetic episodes

123 (60%)

96 (47%)

≥ 0.01

Failure a

83 (40%)

110 (53%)

Nausea assessments b:

Number of patients

185

191

None

119 (64%)

99 (52%)

≥ 0.01

a Failure was one or more emetic episodes, rescued, or withdrawn.

b Nausea measured as none, mild, or severe.

A double-blind, multicenter, placebo-controlled trial was conducted in 670 pediatric patients aged 1 month to 24 months who were undergoing routine surgery under general anesthesia. Seventy-five percent (75%) were males; 64% were white, 15% were black, 13% were American Hispanic, 2% were Asian, and 6% were “other race” patients. A single 0.1-mg/kg intravenous dose of ondansetron administered within 5 minutes following induction of anesthesia was statistically significantly more effective than placebo in preventing vomiting. In the placebo group, 28% of patients experienced vomiting compared with 11% of subjects who received ondansetron ( P ≤ 0.01). Overall, 32 (10%) of placebo patients and 18 (5%) of patients who received ondansetron received antiemetic rescue medication(s) or prematurely withdrew from the trial.

Prevention of Further Postoperative Nausea and Vomiting

Adults

Adult surgical patients receiving general balanced anesthesia (barbiturate: thiopental, methohexital, or thiamylal; opioid: alfentanil or fentanyl; nitrous oxide; neuromuscular blockade: succinylcholine/curare and/or vecuronium or atracurium; and supplemental isoflurane) who received no prophylactic antiemetics and who experienced nausea and/or vomiting within 2 hours postoperatively were evaluated in two double-blind US trials involving 441 patients. Patients who experienced an episode of postoperative nausea and/or vomiting were given Ondansetron Injection (4 mg) intravenously over 2 to 5 minutes, and this was significantly more effective than placebo. The results of these trials are summarized in Table 12.

Table 12. Therapeutic Response in Prevention of Further Postoperative Nausea and Vomiting in Adult Patients

Ondansetron 4 mg Intravenous

Placebo

P Value

Study 1

Emetic episodes:

Number of patients

104

117

Treatment response 24 h after study drug

  • 0 Emetic episodes

49 (47%)

19 (16%)

< 0.001

  • 1 Emetic episode

12 (12%)

9 (8%)

  • More than 1 emetic episode/rescued

43 (41%)

89 (76%)

Median time to first emetic episode (min) a

55.0

43.0

Nausea assessments:

Number of patients

98

102

Mean nausea score over 24-h postoperative period b

1.7

3.1

Study 2

Emetic episodes:

Number of patients

112

108

Treatment response 24 h after study drug

  • 0 Emetic episodes

49 (44%)

28 (26%)

0.006

  • 1 Emetic episode

14 (13%)

3 (3%)

  • More than 1 emetic episode/rescued

49 (44%)

77 (71%)

Median time to first emetic episode (min) a

60.5

34.0

Nausea assessments:

Number of patients

105

85

Mean nausea score over 24-h postoperative period b

1.9

2.9

a After administration of study drug.

b Nausea measured on a scale of 0-10 with 0 = no nausea, 10 = nausea as bad as it can be.

The populations in Table 12 consisted mainly of women undergoing laparoscopic procedures.

Repeat Dosing in Adults: In patients who do not achieve adequate control of postoperative nausea and vomiting following a single, prophylactic, preinduction, intravenous dose of ondansetron 4 mg, administration of a second intravenous dose of ondansetron 4 mg postoperatively does not provide additional control of nausea and vomiting.

Pediatrics

One double-blind, placebo-controlled, US trial was performed in 351 male and female outpatients (aged 2 to 12 years) who received general anesthesia with nitrous oxide and no prophylactic antiemetics. Surgical procedures were unrestricted. Patients who experienced two or more emetic episodes within 2 hours following discontinuation of nitrous oxide were randomized to either single intravenous doses of ondansetron (0.1 mg/kg for pediatric patients weighing 40 kg or less, 4 mg for pediatric patients weighing more than 40 kg) or placebo administered over at least 30 seconds. Ondansetron was significantly more effective than placebo in preventing further episodes of nausea and vomiting. The results of the trial are summarized in Table 13.

Table 13. Therapeutic Response in Prevention of Further Postoperative Nausea and Vomiting in Pediatric Patients Aged 2 to 12 Years

Treatment Response Over 24 Hours

Ondansetron

n (%)

Placebo

n (%)

P Value

Number of patients

180

171

0 Emetic episodes

96 (53%)

29 (17%)

≥ 0.001

Failure a

84 (47%)

142 (83%)

a Failure was one or more emetic episodes, rescued, or withdrawn.

How Supplied/Storage and Handling

Ondansetron Injection USP, 2 mg/mL, is supplied as follows:

NDC 16729-298-05       20-mL multiple-dose vial (Singles)

Storage: Store at 20˚C to 25˚C (68˚F to 77˚F); excursions permitted to 15˚C to 30˚C (59˚F to 86˚F). [See USP Controlled Room Temperature.] Protect from light.

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