ONDANSETRON  - ondansetron tablet, orally disintegrating 
Aurobindo Pharma Limited

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Ondansetron Orally Disintegrating Tablets, USP

DESCRIPTION


3

Chemical Structure

18 19 3



CLINICAL PHARMACOLOGY

Pharmacodynamics


3 3 3

3



Pharmacokinetics








In vitro
max ½ 1 PRECAUTIONS: Drug Interactions





Table 1. Pharmacokinetics in Normal Volunteers: Single 8 mg Ondansetron Hydrochloride Tablet Dose
Age-group
(years)
Mean Weight
(kg)
   n     Peak Plasma
Concentration
(ng/mL)
Time of Peak
Plasma
Concentration
(h)
Mean Elimination
Half-life
(h)
Systemic
Plasma Clearance
L/h/kg
Absolute
Bioavailability
18-40 M
69
6
26.2
2
3.1
0.403
0.483
F
62.7
5
42.7
1.7
3.5
0.354
0.663
 61-74 M
77.5
6
24.1
2.1
4.1
0.384
0.585
 F
60.2
6
52.4
1.9
4.9
0.255
0.643
≥75 M
78
5
37
2.2
4.5
0.277
0.619
F
67.6
6
46.1
2.1
6.2
0.249
0.747

Table 2. Pharmacokinetics in Normal Volunteers: Single 24 mg Ondansetron Hydrochloride Tablet Dose
Age-group
(years)
Mean Weight
(kg)
   n    Peak Plasma
Concentration
(ng/mL)
Time of Peak
Plasma Concentration
(h)
Mean Elimination
Half-life
(h)
18-43 M
84.1
8
125.8
1.9
4.7
F
71.8
8
194.4
1.6
5.8



2



in vitro

Clinical Trials

Chemotherapy-Induced Nausea and Vomiting

Highly Emetogenic Chemotherapy


2 2

2

P

2

Moderately Emetogenic Chemotherapy



Table 3. Emetic Episodes: Treatment Response
  Ondansetron
8 mg b.i.d.
Ondansetron
Hydrochloride Tablets*
Placebo P Value
* The first dose was administered 30 minutes before the start of emetogenic chemotherapy, with a subsequent dose 8 hours after the first dose. An 8 mg ondansetron hydrochloride tablet was administered twice a day for 2 days after completion of chemotherapy.
Median undefined since at least 50% of the patients were withdrawn or had more than 2 emetic episodes.
Median undefined since at least 50% of patients did not have any emetic episodes.
   Number of patients
33
34
   Treatment response
      0 Emetic episodes
20 (61%)
2 (6%)
<0.001
      1 to 2 Emetic episodes
6 (18%)
8 (24%)
   More than 2 emetic episodes/withdrawn
7 (21%)
24 (71%)
<0.001
   Median number of emetic episodes
0
Undefined
   Median time to first emetic episode (h)
Undefined
6.5


Table 4. Emetic Episodes: Treatment Response
Ondansetron
8 mg b.i.d.
Ondansetron
Hydrochloride
Tablets*
8 mg t.i.d.
Ondansetron
Hydrochloride
Tablets†
* The first dose was administered 30 minutes before the start of emetogenic chemotherapy, with a subsequent dose 8 hours after the first dose. An 8 mg ondansetron hydrochloride tablet was administered twice a day for 2 days after completion of chemotherapy.
The first dose was administered 30 minutes before the start of emetogenic chemotherapy, with subsequent doses 4 and 8 hours after the first dose. An 8 mg ondansetron hydrochloride tablet was administered 3 times a day for 2 days after completion of chemotherapy.
Median undefined since at least 50% of patients did not have any emetic episodes.
§ Visual analog scale assessment: 0 = no nausea, 100 = nausea as bad as it can be.
   Number of patients
165
171
   Treatment response
      0 Emetic episodes
101 (61%)
99 (58%)
      1 to 2 Emetic episodes
16 (10%)
17 (10%)
      More than 2 emetic episodes/withdrawn
48 (29%)
55 (32%)
   Median number of emetic episodes
0
0
   Median time to first emetic episode (h)
Undefined
Undefined
   Median nausea scores (0 to 100)§
6
6

Re-treatment


Pediatric Studies


Radiation-Induced Nausea and Vomiting

Total Body Irradiation


Single High-Dose Fraction Radiotherapy


2

Daily Fractionated Radiotherapy


2

Postoperative Nausea and Vomiting




INDICATIONS AND USAGE

 

  1. Prevention of nausea and vomiting associated with highly emetogenic cancer chemotherapy, including cisplatin ≥50 mg/m2.
  2. Prevention of nausea and vomiting associated with initial and repeat courses of moderately emetogenic cancer chemotherapy.
  3. Prevention of nausea and vomiting associated with radiotherapy in patients receiving either total body irradiation, single high-dose fraction to the abdomen, or daily fractions to the abdomen.
  4. Prevention of postoperative nausea and/or vomiting. As with other antiemetics, routine prophylaxis is not recommended for 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 postoperatively, ondansetron orally disintegrating tablets are recommended even where the incidence of postoperative nausea and/or vomiting is low.

CONTRAINDICATIONS




WARNINGS


3

PRECAUTIONS

General




Information for Patients

Phenylketonurics




Drug Interactions


CLINICAL PHARMACOLOGY, Pharmacokinetics



CONTRAINDICATIONS

Phenytoin, Carbamazepine, and Rifampicin


1,3

Tramadol


4,5

Chemotherapy




Use in Surgical Patients


Carcinogenesis, Mutagenesis, Impairment of Fertility


Pregnancy

Teratogenic Effects

Pregnancy Category B


Nursing Mothers


Pediatric Use


CLINICAL PHARMACOLOGY DOSAGE AND ADMINISTRATION

Geriatric Use


CLINICAL PHARMACOLOGY

ADVERSE REACTIONS


Chemotherapy-Induced Nausea and Vomiting


2

Table 5. Principal Adverse Events in U.S. Trials: Single Day Therapy With 24 mg Ondansetron Hydrochloride Tablets (Highly Emetogenic Chemotherapy)
Event Ondansetron
24 mg q.d.
n = 300
Ondansetron
8 mg b.i.d.
n = 124
Ondansetron
32 mg q.d.
n = 117
   Headache
33 (11%)
16 (13%)
17 (15%)
   Diarrhea
13 (4%)
9 (7%)
3 (3%)

Table 6. Principal Adverse Events in U.S. Trials: 3 Days of Therapy With 8 mg Ondansetron Hydrochloride Tablets (Moderately Emetogenic Chemotherapy)
Event Ondansetron
8 mg b.i.d.
n = 242
Ondansetron
8 mg t.i.d.
n = 415
Placebo
n = 262
   Headache
58 (24%)
113 (27%)
34 (13%)
   Malaise/fatigue
32 (13%)
37 (9%)
6 (2%)
   Constipation
22 (9%)
26 (6%)
1 (<1%)
   Diarrhea
15 (6%)
16 (4%)
10 (4%)
   Dizziness
13 (5%)
18 (4%)
12 (5%)

Central Nervous System


Hepatic




Integumentary


Other


Radiation-Induced Nausea and Vomiting


Postoperative Nausea and Vomiting




Table 7. Frequency of Adverse Events From Controlled Studies With Ondansetron Hydrochloride Tablets (Postoperative Nausea and Vomiting)
Adverse Event Ondansetron 16 mg
(n = 550)
Placebo
(n = 531)
   Wound problem
152 (28%)
162 (31%)
   Drowsiness/sedation
112 (20%)
122 (23%)
   Headache
49 (9%)
27 (5%)
   Hypoxia
49 (9%)
35 (7%)
   Pyrexia
45 (8%)
34 (6%)
   Dizziness
36 (7%)
34 (6%)
   Gynecological disorder
36 (7%)
33 (6%)
   Anxiety/agitation
33 (6%)
29 (5%)
   Bradycardia
32 (6%)
30 (6%)
   Shiver(s)
28 (5%)
30 (6%)
   Urinary retention
28 (5%)
18 (3%)
   Hypotension
27 (5%)
32 (6%)
   Pruritus
27 (5%)
20 (4%)

Observed During Clinical Practice




Cardiovascular:


General:


Hepatobiliary:


Lower Respiratory:


Neurology:


Skin:


Special Senses: Eye Disorders:

DRUG ABUSE AND DEPENDENCE


OVERDOSAGE




DOSAGE AND ADMINISTRATION

Instructions for Use/Handling Ondansetron Orally Disintegrating Tablets


Prevention of Nausea and Vomiting Associated With Highly Emetogenic Cancer Chemotherapy


2

Pediatric Use


Geriatric Use


Prevention of Nausea and Vomiting Associated With Moderately Emetogenic Cancer Chemotherapy


Pediatric Use


Geriatric Use


Prevention of Nausea and Vomiting Associated With Radiotherapy, Either Total Body Irradiation, or Single High-Dose Fraction or Daily Fractions to the Abdomen




For total body irradiation


For single high-dose fraction radiotherapy to the abdomen


For daily fractionated radiotherapy to the abdomen

Pediatric Use


Geriatric Use


Postoperative Nausea and Vomiting


Pediatric Use


Geriatric Use


Dosage Adjustment for Patients With Impaired Renal Function


Dosage Adjustment for Patients With Impaired Hepatic Function


2

HOW SUPPLIED


Ondansetron Orally Disintegrating Tablets USP, 4 mg




Ondansetron Orally Disintegrating Tablets USP, 8 mg




Store at

REFERENCES

  1. Britto MR, Hussey EK, Mydlow P, et al. Effect of enzyme inducers on ondansetron (OND) metabolism in humans. Clin Pharmacol Ther. 1997;61:228.
  2. Pugh RNH, Murray-Lyon IM, Dawson JL, Pietroni MC, Williams R. Transection of the oesophagus for bleeding oesophageal varices. Brit J Surg. 1973;60:646-649.
  3. Villikka K, Kivisto KT, Neuvonen PJ. The effect of rifampin on the pharmacokinetics of oral and intravenous ondansetron. Clin Pharmacol Ther. 1999;65:377-381.
  4. De Witte JL, Schoenmaekers B, Sessler DI, et al. Anesth Analg. 2001;92:1319-1321.
  5. Arcioni R, della Rocca M, Romanò R, et al. Anesth Analg. 2002;94:1553-1557.


Aurobindo Pharma USA, Inc.




Aurobindo Pharma Limited


PACKAGE LABEL-PRINCIPAL DISPLAY PANEL - 4 mg (10,000 Tablet Bottle)


NDC 65862-390-19
Ondansetron Orally
Disintegrating Tablets, USP

4 mg
Rx only             10,000 Tablets
AUROBINDO
PACKAGE LABEL-PRINCIPAL DISPLAY PANEL - 4 mg (10,000 Tablet Bottle)

PACKAGE LABEL-PRINCIPAL DISPLAY PANEL - 4 mg Blister Carton (3 x 10 Unit-dose)


Rx only                                   NDC 65862-390-10
Ondansetron Orally Disintegrating Tablets, USP
4 mg
30 Tablets (3 blister cards each containing 10 tablets)
AUROBINDO
PACKAGE LABEL-PRINCIPAL DISPLAY PANEL - 4 mg Blister Carton (3 x 10 Unit-dose)

PACKAGE LABEL-PRINCIPAL DISPLAY PANEL - 8 mg (6,000 Tablet Bottle)


NDC 65862-391-66
Ondansetron Orally
Disintegrating Tablets, USP

8 mg
Rx only             6,000 Tablets
AUROBINDO
PACKAGE LABEL-PRINCIPAL DISPLAY PANEL - 8 mg (6,000 Tablet Bottle)

PACKAGE LABEL-PRINCIPAL DISPLAY PANEL - 8 mg Blister Carton (3 x 10 Unit-dose)


Rx only                                   NDC 65862-391-10
Ondansetron Orally Disintegrating Tablets, USP
8 mg
30 Tablets (3 blister cards each containing 10 tablets)
AUROBINDO
PACKAGE LABEL-PRINCIPAL DISPLAY PANEL - 8 mg Blister Carton (3 x 10 Unit-dose)

ONDANSETRON 
ondansetron   tablet, orally disintegrating
Product Information
Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 65862-390
Route of Administration ORAL DEA Schedule     
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
ONDANSETRON (ONDANSETRON) ONDANSETRON 4 mg
Inactive Ingredients
Ingredient Name Strength
MANNITOL  
CROSPOVIDONE  
LACTOSE MONOHYDRATE  
CELLULOSE, MICROCRYSTALLINE  
ASPARTAME  
SILICON DIOXIDE  
MAGNESIUM STEARATE  
Product Characteristics
Color WHITE (White to Off-white) Score no score
Shape ROUND Size 5mm
Flavor STRAWBERRY, GUARANA Imprint Code 5;E
Contains     
Packaging
# NDC Package Description Multilevel Packaging
1 65862-390-19 10000 TABLET In 1 BOTTLE None
2 65862-390-10 3 BLISTER PACK In 1 CARTON contains a BLISTER PACK
2 10 TABLET In 1 BLISTER PACK This package is contained within the CARTON (65862-390-10)

Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
ANDA ANDA090469 04/12/2010

ONDANSETRON 
ondansetron   tablet, orally disintegrating
Product Information
Product Type HUMAN PRESCRIPTION DRUG NDC Product Code (Source) 65862-391
Route of Administration ORAL DEA Schedule     
Active Ingredient/Active Moiety
Ingredient Name Basis of Strength Strength
ONDANSETRON (ONDANSETRON) ONDANSETRON 8 mg
Inactive Ingredients
Ingredient Name Strength
MANNITOL  
CROSPOVIDONE  
LACTOSE MONOHYDRATE  
CELLULOSE, MICROCRYSTALLINE  
ASPARTAME  
SILICON DIOXIDE  
MAGNESIUM STEARATE  
Product Characteristics
Color WHITE (White to Off-white) Score no score
Shape ROUND Size 7mm
Flavor STRAWBERRY, GUARANA Imprint Code 7;E
Contains     
Packaging
# NDC Package Description Multilevel Packaging
1 65862-391-66 6000 TABLET In 1 BOTTLE None
2 65862-391-10 3 BLISTER PACK In 1 CARTON contains a BLISTER PACK
2 10 TABLET In 1 BLISTER PACK This package is contained within the CARTON (65862-391-10)

Marketing Information
Marketing Category Application Number or Monograph Citation Marketing Start Date Marketing End Date
ANDA ANDA090469 04/12/2010

Labeler - Aurobindo Pharma Limited (650082092)
Establishment
Name Address ID/FEI Operations
Aurobindo Pharma Limited 918917642 MANUFACTURE
Revised: 12/2010 Aurobindo Pharma Limited