RIZATRIPTAN BENZOATE
Generic: RIZATRIPTAN BENZOATE
Basic Information
Manufacturer
Panacea Biotec Limited
Product Type
HUMAN PRESCRIPTION DRUG
Route of Administration
ORAL
FDA Set ID
9c70370d-72ac-e062-e25c-97d57e6397ab
Indications & Usage
1 INDICATIONS AND USAGE Rizatriptan Benzoate Orally Disintegrating Tablets are indicated for the acute treatment of migraine with or without aura in adults and in pediatric patients 6 to 17 years old.
Limitations of Use Rizatriptan benzoate orally disintegrating tablets should only be used where a clear diagnosis of migraine has been established.
If a patient has no response for the first migraine attack treated with rizatriptan benzoate orally disintegrating tablets, USP, the diagnosis of migraine should be reconsidered before rizatriptan benzoate orally disintegrating tablets, USP are administered to treat any subsequent attacks.
Rizatriptan benzoate orally disintegrating tablets are not indicated for use in the management of hemiplegic or basilar migraine [see Contraindications (4) ] .
Rizatriptan benzoate orally disintegrating tablets are not indicated for the prevention of migraine attacks.
Safety and effectiveness of Rizatriptan benzoate orally disintegrating tablets have not been established for cluster headache.
Rizatriptan benzoate is a serotonin (5-HT) 1B/1D receptor agonist (triptan) indicated for the acute treatment of migraine with or without aura in adults and in pediatric patients 6 to 17 years of age ( 1 ) Limitations of Use : Use only after clear diagnosis of migraine has been established ( 1 ) Not indicated for the prophylactic therapy of migraine ( 1 ) Not indicated for the treatment of cluster headache ( 1 )
Limitations of Use Rizatriptan benzoate orally disintegrating tablets should only be used where a clear diagnosis of migraine has been established.
If a patient has no response for the first migraine attack treated with rizatriptan benzoate orally disintegrating tablets, USP, the diagnosis of migraine should be reconsidered before rizatriptan benzoate orally disintegrating tablets, USP are administered to treat any subsequent attacks.
Rizatriptan benzoate orally disintegrating tablets are not indicated for use in the management of hemiplegic or basilar migraine [see Contraindications (4) ] .
Rizatriptan benzoate orally disintegrating tablets are not indicated for the prevention of migraine attacks.
Safety and effectiveness of Rizatriptan benzoate orally disintegrating tablets have not been established for cluster headache.
Rizatriptan benzoate is a serotonin (5-HT) 1B/1D receptor agonist (triptan) indicated for the acute treatment of migraine with or without aura in adults and in pediatric patients 6 to 17 years of age ( 1 ) Limitations of Use : Use only after clear diagnosis of migraine has been established ( 1 ) Not indicated for the prophylactic therapy of migraine ( 1 ) Not indicated for the treatment of cluster headache ( 1 )
Adverse Reactions
6 ADVERSE REACTIONS The following adverse reactions are discussed in more detail in other sections of the labeling: Myocardial Ischemia, Myocardial Infarction, and Prinzmetal's Angina [see Warnings and Precautions (5.1) ] .
Arrhythmias [see Warnings and Precautions (5.2) ] .
Chest and or Throat, Neck and/or Jaw Pain/ Tightness/ Pressure [see Warnings and Precautions (5.3) ] .
Cerebrovascular Events [see Warnings and Precautions (5.4) ] .
Other Vasospasm Reactions [see Warnings and Precautions (5.5) ] .
Medication Overuse Headache [see Warnings and Precautions (5.6) ] .
Serotonin Syndrome [see Warnings and Precautions (5.7) ] .
Increase in Blood Pressure [see Warnings and Precautions (5.8) ] .
The most common adverse reactions in adults were (incidence ≥ 5% and greater than placebo): asthenia/fatigue, somnolence, pain/pressure sensation and dizziness ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Bionpharma, Inc.
at 1-888-235-BION or 1-888-235-2466 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .
6.1 Clinical Trials Experience Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice.
Adults Incidence in Controlled Clinical Trials Adverse reactions to Rizatriptan benzoate were assessed in controlled clinical trials that included over 3,700 adult patients who received single or multiple doses ofRizatriptan benzoate.
The most common adverse reactions during treatment with Rizatriptan benzoate (≥ 5% in either treatment group and greater than placebo) were asthenia/fatigue, somnolence, pain/pressure sensation and dizziness.
These adverse reactions appeared to be dose relatedTable 1 lists the adverse reactions (incidence ≥ 2% and greater than placebo) after a single dose of Rizatriptan benzoate in adults.
Table 1 lists the adverse reactions (incidence ≥ 2% and greater than placebo) after a single dose of Rizatriptan benzoate in adults Table 1: Incidence (≥2% and Greater than Placebo) of Adverse Reactions After a Single Dose of Rizatriptan Benzoate or Placebo in Adults % of Patients Rizatriptan Rizatriptan Benzoate Benzoate Placebo Adverse Reactions 5 mg 10 mg (N = 627) (N = 977) (N = 1167) Atypical Sensations 4 5 4 Paresthesia 3 4 <2 Pain and other Pressure Sensations 6 9 3 Chest Pain: tightness/pressure and/or heaviness <2 3 1 Neck/throat/jaw: pain/tightness/pressure <2 2 1 Regional Pain: tightness/pressure and/or heaviness <1 2 0 Pain, location unspecified 3 3 <2 Digestive 9 13 8 Dry Mouth 3 3 1 Nausea 4 6 4 Neurological 14 20 11 Dizziness 4 9 5 Headache <2 2 <1 Somnolence 4 8 4 Other Asthenia/fatigue 4 7 2 The frequencies of adverse reactions in clinical trials did not increase when up to three doses were taken within 24 hours.
Adverse reaction frequencies were also unchanged by concomitant use of drugs commonly taken for migraine prophylaxis (including propranolol), oral contraceptives, or analgesics.
The incidences of adverse reactions were not affected by age or gender.
There were insufficient data to assess the impact of race on the incidence of adverse reactions.
Other Events Observed in Association with the Administration of Rizatriptan Benzoate in Adults In the following section, the frequencies of less commonly reported adverse events are presented that were not reported in other sections of the labeling.
Because the reports include events observed in open studies, the role of Rizatriptan benzoate in their causation cannot be reliably determined.
Furthermore, variability associated with adverse event reporting, the terminology used to describe adverse events, limit the value of the quantitative frequency estimates provided.
Event frequencies are calculated as the number of patients who used Rizatriptan benzoate and reported an event divided by the total number of patients exposed to Rizatriptan benzoate (N = 3,716).
All reported events occurred at an incidence ≥1%, or are believed to be reasonably associated with the use of the drug.
Events are further classified within body system categories and enumerated in order of decreasing frequency using the following definitions: frequent adverse events are those defined as those occurring in at least (>) 1/100 patients; infrequent adverse experiences are those occurring in 1/100 to 1/1000 patients; and rare adverse experiences are those occurring in fewer than 1/1000 patients General: Infrequent was facial edema.
Rare were syncope and edema/swelling Atypical Sensations: Frequent were warm sensations Cardiovascular: Frequent was palpitation.
Infrequent were tachycardia, cold extremities, and bradycardia Digestive: Frequent were diarrhea and vomiting.
Infrequent were dyspepsia, tongue edema and abdominal distention Musculoskeletal: Infrequent were muscle weakness, stiffness, myalgia and muscle cramp/spasm Neurological/Psychiatric: Frequent were hypoesthesia, euphoria and tremor.
Infrequent were vertigo, insomnia, confusion/disorientation, gait abnormality, memory impairment, and agitation Respiratory: Frequent was dyspnea.
Infrequent was pharyngeal edema Special Senses: Infrequent were blurred vision and tinnitus.
Rare was eye swelling Skin and Skin Appendage: Frequent was flushing.
Infrequent were sweating, pruritus, rash, and urticaria.
Rare was erythema, hot flashes.
The adverse reaction profile seen with Rizatriptan benzoate orally disintegrating tablets was similar to that seen with Rizatriptan benzoate tablets.
Pediatric Patients 6 to 17 Years of Age Incidence in Controlled Clinical Trials in Pediatric Patients Adverse reactions to Rizatriptan benzoate were assessed in a controlled clinical trial in the acute treatment of migraines (Study 7) that included a total of 1382 pediatric patients 6-17 years of age, of which 977 (72%) administered at least one dose of study treatment (Rizatriptan benzoate and/or placebo) [see Clinical Studies (14.2) ] .
The incidence of adverse reactions reported for pediatric patients in the acute clinical trial was similar in patients who received Rizatriptan benzoate to those who received placebo.
The adverse reaction pattern in pediatric patients is expected to be similar to that in adults.
Other Events Observed in Association with the Administration of Rizatriptan benzoate in Pediatric Patients In the following section, the frequencies of less commonly reported adverse events are presented.
Because the reports include events observed in open studies, the role of Rizatriptan benzoate in their causation cannot be reliably determined.
Furthermore, variability associated with adverse event reporting, the terminology used to describe adverse events, limit the value of the quantitative frequency estimates provided.
Event frequencies are calculated as the number of pediatric patients 6 to 17 years of age who used Rizatriptan benzoate and reported an event divided by the total number of patients exposed to rizatriptan benzoate orally disintegrating tablets, USP (N=1068).
All reported events occurred at an incidence ≥1%, or are believed to be reasonably associated with the use of the drug.
Events are further classified within system organ class and enumerated in order of decreasing frequency using the following definitions: frequent adverse events are those occurring in (>)1/100 pediatric patients; infrequent adverse experiences are those occurring in 1/100 to 1/1000 pediatric patients; and rare adverse experiences are those occurring in fewer than 1/1000 patients General: Frequent was fatigue.
Ear and labyrinth disorders: Infrequent was hypoacusis.
Gastrointestinal disorders: Frequent was abdominal discomfort.
Nervous system disorders: Infrequent were coordination abnormal, disturbance in attention, and presyncope.
Psychiatric disorders: Infrequent was hallucination.
6.2 Postmarketing Experience The following section enumerates potentially important adverse events that have occurred in clinical practice and which have been reported spontaneously to various surveillance systems.
The events enumerated include all except those already listed in other sections of the labeling or those too general to be informative.
Because the reports cite events reported spontaneously from worldwide post-marketing experience, frequency of events and the role of Rizatriptan benzoate in their causation cannot be reliably determined.
Neurological/Psychiatric: Seizure.
General: Allergic conditions including anaphylaxis/ anaphylactoid reaction, angioedema, wheezing, and toxic epidermal necrolysis [see Contraindications (4) ] .
Special Senses: Dysgeusia.
Arrhythmias [see Warnings and Precautions (5.2) ] .
Chest and or Throat, Neck and/or Jaw Pain/ Tightness/ Pressure [see Warnings and Precautions (5.3) ] .
Cerebrovascular Events [see Warnings and Precautions (5.4) ] .
Other Vasospasm Reactions [see Warnings and Precautions (5.5) ] .
Medication Overuse Headache [see Warnings and Precautions (5.6) ] .
Serotonin Syndrome [see Warnings and Precautions (5.7) ] .
Increase in Blood Pressure [see Warnings and Precautions (5.8) ] .
The most common adverse reactions in adults were (incidence ≥ 5% and greater than placebo): asthenia/fatigue, somnolence, pain/pressure sensation and dizziness ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Bionpharma, Inc.
at 1-888-235-BION or 1-888-235-2466 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .
6.1 Clinical Trials Experience Because clinical studies are conducted under widely varying conditions, adverse reaction rates observed in the clinical studies of a drug cannot be directly compared to rates in the clinical studies of another drug and may not reflect the rates observed in practice.
Adults Incidence in Controlled Clinical Trials Adverse reactions to Rizatriptan benzoate were assessed in controlled clinical trials that included over 3,700 adult patients who received single or multiple doses ofRizatriptan benzoate.
The most common adverse reactions during treatment with Rizatriptan benzoate (≥ 5% in either treatment group and greater than placebo) were asthenia/fatigue, somnolence, pain/pressure sensation and dizziness.
These adverse reactions appeared to be dose relatedTable 1 lists the adverse reactions (incidence ≥ 2% and greater than placebo) after a single dose of Rizatriptan benzoate in adults.
Table 1 lists the adverse reactions (incidence ≥ 2% and greater than placebo) after a single dose of Rizatriptan benzoate in adults Table 1: Incidence (≥2% and Greater than Placebo) of Adverse Reactions After a Single Dose of Rizatriptan Benzoate or Placebo in Adults % of Patients Rizatriptan Rizatriptan Benzoate Benzoate Placebo Adverse Reactions 5 mg 10 mg (N = 627) (N = 977) (N = 1167) Atypical Sensations 4 5 4 Paresthesia 3 4 <2 Pain and other Pressure Sensations 6 9 3 Chest Pain: tightness/pressure and/or heaviness <2 3 1 Neck/throat/jaw: pain/tightness/pressure <2 2 1 Regional Pain: tightness/pressure and/or heaviness <1 2 0 Pain, location unspecified 3 3 <2 Digestive 9 13 8 Dry Mouth 3 3 1 Nausea 4 6 4 Neurological 14 20 11 Dizziness 4 9 5 Headache <2 2 <1 Somnolence 4 8 4 Other Asthenia/fatigue 4 7 2 The frequencies of adverse reactions in clinical trials did not increase when up to three doses were taken within 24 hours.
Adverse reaction frequencies were also unchanged by concomitant use of drugs commonly taken for migraine prophylaxis (including propranolol), oral contraceptives, or analgesics.
The incidences of adverse reactions were not affected by age or gender.
There were insufficient data to assess the impact of race on the incidence of adverse reactions.
Other Events Observed in Association with the Administration of Rizatriptan Benzoate in Adults In the following section, the frequencies of less commonly reported adverse events are presented that were not reported in other sections of the labeling.
Because the reports include events observed in open studies, the role of Rizatriptan benzoate in their causation cannot be reliably determined.
Furthermore, variability associated with adverse event reporting, the terminology used to describe adverse events, limit the value of the quantitative frequency estimates provided.
Event frequencies are calculated as the number of patients who used Rizatriptan benzoate and reported an event divided by the total number of patients exposed to Rizatriptan benzoate (N = 3,716).
All reported events occurred at an incidence ≥1%, or are believed to be reasonably associated with the use of the drug.
Events are further classified within body system categories and enumerated in order of decreasing frequency using the following definitions: frequent adverse events are those defined as those occurring in at least (>) 1/100 patients; infrequent adverse experiences are those occurring in 1/100 to 1/1000 patients; and rare adverse experiences are those occurring in fewer than 1/1000 patients General: Infrequent was facial edema.
Rare were syncope and edema/swelling Atypical Sensations: Frequent were warm sensations Cardiovascular: Frequent was palpitation.
Infrequent were tachycardia, cold extremities, and bradycardia Digestive: Frequent were diarrhea and vomiting.
Infrequent were dyspepsia, tongue edema and abdominal distention Musculoskeletal: Infrequent were muscle weakness, stiffness, myalgia and muscle cramp/spasm Neurological/Psychiatric: Frequent were hypoesthesia, euphoria and tremor.
Infrequent were vertigo, insomnia, confusion/disorientation, gait abnormality, memory impairment, and agitation Respiratory: Frequent was dyspnea.
Infrequent was pharyngeal edema Special Senses: Infrequent were blurred vision and tinnitus.
Rare was eye swelling Skin and Skin Appendage: Frequent was flushing.
Infrequent were sweating, pruritus, rash, and urticaria.
Rare was erythema, hot flashes.
The adverse reaction profile seen with Rizatriptan benzoate orally disintegrating tablets was similar to that seen with Rizatriptan benzoate tablets.
Pediatric Patients 6 to 17 Years of Age Incidence in Controlled Clinical Trials in Pediatric Patients Adverse reactions to Rizatriptan benzoate were assessed in a controlled clinical trial in the acute treatment of migraines (Study 7) that included a total of 1382 pediatric patients 6-17 years of age, of which 977 (72%) administered at least one dose of study treatment (Rizatriptan benzoate and/or placebo) [see Clinical Studies (14.2) ] .
The incidence of adverse reactions reported for pediatric patients in the acute clinical trial was similar in patients who received Rizatriptan benzoate to those who received placebo.
The adverse reaction pattern in pediatric patients is expected to be similar to that in adults.
Other Events Observed in Association with the Administration of Rizatriptan benzoate in Pediatric Patients In the following section, the frequencies of less commonly reported adverse events are presented.
Because the reports include events observed in open studies, the role of Rizatriptan benzoate in their causation cannot be reliably determined.
Furthermore, variability associated with adverse event reporting, the terminology used to describe adverse events, limit the value of the quantitative frequency estimates provided.
Event frequencies are calculated as the number of pediatric patients 6 to 17 years of age who used Rizatriptan benzoate and reported an event divided by the total number of patients exposed to rizatriptan benzoate orally disintegrating tablets, USP (N=1068).
All reported events occurred at an incidence ≥1%, or are believed to be reasonably associated with the use of the drug.
Events are further classified within system organ class and enumerated in order of decreasing frequency using the following definitions: frequent adverse events are those occurring in (>)1/100 pediatric patients; infrequent adverse experiences are those occurring in 1/100 to 1/1000 pediatric patients; and rare adverse experiences are those occurring in fewer than 1/1000 patients General: Frequent was fatigue.
Ear and labyrinth disorders: Infrequent was hypoacusis.
Gastrointestinal disorders: Frequent was abdominal discomfort.
Nervous system disorders: Infrequent were coordination abnormal, disturbance in attention, and presyncope.
Psychiatric disorders: Infrequent was hallucination.
6.2 Postmarketing Experience The following section enumerates potentially important adverse events that have occurred in clinical practice and which have been reported spontaneously to various surveillance systems.
The events enumerated include all except those already listed in other sections of the labeling or those too general to be informative.
Because the reports cite events reported spontaneously from worldwide post-marketing experience, frequency of events and the role of Rizatriptan benzoate in their causation cannot be reliably determined.
Neurological/Psychiatric: Seizure.
General: Allergic conditions including anaphylaxis/ anaphylactoid reaction, angioedema, wheezing, and toxic epidermal necrolysis [see Contraindications (4) ] .
Special Senses: Dysgeusia.