Rizatriptan Benzoate
Tablet · Oral
Uses
Rizatriptan benzoate 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 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 tablets, the diagnosis of migraine should be reconsidered before rizatriptan benzoate tablets are administered to treat any subsequent attacks. Rizatriptan benzoate tablets are not indicated for use in the management of hemiplegic or basilar migraine [see Contraindications (4) ] . Rizatriptan benzoate tablets are not indicated for the prevention of migraine attacks. Safety and effectiveness of rizatriptan benzoate tablets have not been established for cluster headache. Rizatriptan benzoate tablets are 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 )
Dosage and administration
Adults: 5 or 10 mg single dose; separate repeat doses by at least two hours; maximum dose in a 24-hour period: 30 mg ( 2.1 ) Pediatric patients 6 to 17 years: 5 mg single dose in patients less than 40 kg (88 lb); 10 mg single dose in patients 40 kg (88 lb) or more ( 2.2 ) Adjust dose if co-administered with propranolol ( 2.4 ) 2.1 Dosing Information in Adults The recommended starting dose of rizatriptan benzoate tablets are either 5 mg or 10 mg for the acute treatment of migraines in adults. The 10-mg dose may provide a greater effect than the 5-mg dose, but may have a greater risk of adverse reactions [see Clinical Studies (14.1) ] . Redosing in Adults Although the effectiveness of a second dose or subsequent doses has not been established in placebo-controlled trials, if the migraine headache returns, a second dose may be administered 2 hours after the first dose. The maximum daily dose should not exceed 30 mg in any 24-hour period. The safety of treating, on average, more than four headaches in a 30-day period has not been established. 2.2 Dosing Information in Pediatric Patients (Age 6 to 17 Years) Dosing in pediatric patients is based on the patient's body weight. The recommended dose of rizatriptan benzoate tablets is 5 mg in patients weighing less than 40 kg (88 lb), and 10 mg in patients weighing 40 kg (88 lb) or more. The efficacy and safety of treatment with more than one dose of rizatriptan benzoate tablet within 24 hours in pediatric patients 6 to 17 years of age have not been established. 2.4 Dosage Adjustment for Patients on Propranolol Adult Patients In adult patients taking propranolol, only the 5-mg dose of rizatriptan benzoate tablets are recommended, up to a maximum of 3 doses in any 24-hour period (15 mg) [see Drug Interactions (7.1) and Clinical Pharmacology (12.3) ]. Pediatric Patients For pediatric patients weighing 40 kg (88 lb) or more, taking propranolol, only a single 5-mg dose of rizatriptan benzoate tablets is recommended (maximum dose of 5 mg in a 24-hour period). Rizatriptan benzoate tablets should not be prescribed to propranolol-treated pediatric patients who weigh less than 40 kg (88 lb) [see Drug Interactions (7.1) and Clinical Pharmacology (12.3) ].
Dosage forms and strengths
Rizatriptan benzoate Tablets, USP 5 mg tablets are Pale pink colored, capsule shaped uncoated tablets debossed with '388' on one side and plain on other side. 10 mg tablets are Pale pink colored, capsule shaped uncoated tablets debossed with '389' on one side and plain on other side. Rizatriptan Benzoate Tablets, USP: 5 and 10 mg ( 3 )
Contraindications
Rizatriptan benzoate tablets are contraindicated in patients with: Ischemic coronary artery disease (angina pectoris, history of myocardial infarction, or documented silent ischemia), or other significant underlying cardiovascular disease [see Warnings and Precautions (5.1) ]. Coronary artery vasospasm including Prinzmetal's angina [see Warnings and Precautions (5.1) ]. History of stroke or transient ischemic attack (TIA) [see Warnings and Precautions (5.4) ]. Peripheral vascular disease (PVD) [see Warnings and Precautions (5.5) ]. Ischemic bowel disease [see Warnings and Precautions (5.5) ]. Uncontrolled hypertension [see Warnings and Precautions (5.8) ]. Recent use (i.e., within 24 hours) of another 5-HT 1 agonist, ergotamine-containing medication, or ergot-type medication (such as dihydroergotamine or methysergide) [see Drug Interactions ( 7.2 and 7.3 )]. Hemiplegic or basilar migraine [see Indications and Usage (1) ]. Concurrent administration or recent discontinuation (i.e., within 2 weeks) of a MAO-A inhibitor [see Drug Interactions (7.5) and Clinical Pharmacology (12.3) ]. Hypersensitivity to rizatriptan or any of the excipients (angioedema and anaphylaxis seen) [see Adverse Reactions (6.2) ]. History of ischemic heart disease or coronary artery vasospasm ( 4 ) History of stroke or transient ischemic attack ( 4 ) Peripheral vascular disease ( 4 ) Ischemic bowel disease ( 4 ) Uncontrolled hypertension ( 4 ) Recent (within 24 hours) use of another 5-HT 1 agonist (e.g., another triptan), or of an ergotamine-containing medication ( 4 ) Hemiplegic or basilar migraine ( 4 ) MAO-A inhibitor used in the past 2 weeks ( 4 ) Hypersensitivity to rizatriptan or any of the excipients ( 4 )
Warnings and precautions
Myocardial ischemia, myocardial infarction, and Prinzmetal's angina: Perform cardiac evaluation in patients with multiple cardiovascular risk factors ( 5.1 ) Arrhythmias: Discontinue dosing if occurs ( 5.2 ) Chest/throat/neck/jaw pain, tightness, pressure, or heaviness; Generally not associated with myocardial ischemia; Evaluate patients at high risk ( 5.3 ) Cerebral hemorrhage, subarachnoid hemorrhage, and stroke: Discontinue dosing if occurs ( 5.4 ) Gastrointestinal ischemic events, peripheral vasospastic reactions: Discontinue dosing if occurs ( 5.5 ) Medication overuse headache: Detoxification may be necessary ( 5.6 ) Serotonin syndrome: Discontinue dosing if occurs ( 5.7 ) 5.1 Myocardial Ischemia, Myocardial Infarction, and Prinzmetal's Angina Rizatriptan benzoate tablets should not be given to patients with ischemic or vasospastic coronary artery disease. There have been rare reports of serious cardiac adverse reactions, including acute myocardial infarction, occurring within a few hours following administration of rizatriptan benzoate tablets. Some of these reactions occurred in patients without known coronary artery disease (CAD). 5-HT 1 agonists, including rizatriptan benzoate tablets may cause coronary artery vasospasm (Prinzmetal's Angina), even in patients without a history of CAD Triptan-naïve patients who have multiple cardiovascular risk factors (e.g., increased age, diabetes, hypertension, smoking, obesity, strong family history of CAD) should have a cardiovascular evaluation prior to receiving rizatriptan benzoate tablets. If there is evidence of CAD or coronary artery vasospasm, rizatriptan benzoate tablets should not be administered [see Contraindications (4) ]. For patients who have a negative cardiovascular evaluation, consideration should be given to administration of the first rizatriptan benzoate tablets dose in a medically supervised setting and performing an electrocardiogram (ECG) immediately following rizatriptan benzoate tablets administration. Periodic cardiovascular evaluation should be considered in intermittent long-term users of rizatriptan benzoate tablets who have cardiovascular risk factors. 5.2 Arrhythmias Life-threatening disturbances of cardiac rhythm, including ventricular tachycardia and ventricular fibrillation leading to death, have been reported within a few hours following the administration of 5-HT 1 agonists. Discontinue rizatriptan benzoate tablets if these disturbances occur. 5.3 Chest, Throat, Neck and/or Jaw Pain/Tightness/Pressure As with other 5-HT 1 agonists, sensations of tightness, pain, pressure, and heaviness in the precordium, throat, neck and jaw commonly occur after treatment with rizatriptan benzoate tablets and are usually non -cardiac in origin. However, if a cardiac origin is suspected, patients should be evaluated. Patients shown to have CAD and those with Prinzmetal's variant angina should not receive 5-HT 1 agonists. 5.4 Cerebrovascular Events Cerebral hemorrhage, subarachnoid hemorrhage, and stroke have occurred in patients treated with 5-HT1 agonists, and some have resulted in fatalities. In a number of cases, it appears possible that the cerebrovascular events were primary, the 5-HT1 agonist having been administered in the incorrect belief that the symptoms experienced were a consequence of migraine, when they were not. Also, patients with migraine may be at increased risk of certain cerebrovascular events (e.g., stroke, hemorrhage, transient ischemic attack). Discontinue rizatriptan benzoate tablets, USP if a cerebrovascular event occurs. As with other acute migraine therapies, before treating headaches in patients not previously diagnosed as migraineurs, and in migraineurs who present with atypical symptoms, care should be taken to exclude other potentially serious neurological conditions. Rizatriptan benzoate tablets should not be administered to patients with a history of stroke or transient ischemic attack [see Contraindications (4) ] . 5.5 Other Vasospasm Reactions 5-HT 1 agonists, including rizatriptan benzoate tablets, may cause non-coronary vasospastic reactions, such as peripheral vascular ischemia, gastrointestinal vascular ischemia and infarction (presenting with abdominal pain and bloody diarrhea), splenic infarction, and Raynaud's syndrome. In patients who experience symptoms or signs suggestive of non-coronary vasospasm reaction following the use of any 5-HT 1 agonist, the suspected vasospasm reaction should be ruled out before receiving additional rizatriptan benzoate tablets doses. Reports of transient and permanent blindness and significant partial vision loss have been reported with the use of 5-HT 1 agonists. Since visual disorders may be part of a migraine attack, a causal relationship between these events and the use of 5-HT 1 agonists have not been clearly established. 5.6 Medication Overuse Headache Overuse of acute migraine drugs (e.g., ergotamine, triptans, opioids, or a combination of drugs for 10 or more days per month) may lead to exacerbation of headache (medication overuse headache). Medication overuse headache may present as migraine-like daily headaches, or as a marked increase in frequency of migraine attacks. Detoxification of patients, including withdrawal of the overused drugs, and treatment of withdrawal symptoms (which often includes a transient worsening of headache) may be necessary. 5.7 Serotonin Syndrome Serotonin syndrome may occur with triptans, including rizatriptan benzoate tablets particularly during co -administration with selective serotonin reuptake inhibitors (SSRIs), serotonin norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants (TCAs), and MAO inhibitors [see Drug Interactions (7.5) ] .
Side effects
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, 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 Creekwood Pharmaceuticals LLC. at 1-732-344-0220 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 tablets were assessed in controlled clinical trials that included over 3700 adult patients who received single or multiple doses of rizatriptan benzoate tablets. The most common adverse reactions during treatment with rizatriptan benzoate tablets (≥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 related. Table 1 lists the adverse reactions (incidence ≥2% and greater than placebo) after a single dose of rizatriptan benzoate tablets in adults. Table 1: Incidence (≥2% and Greater than Placebo) of Adverse Reactions After a Single Dose of Rizatriptan Benzoate Tablets or Placebo in Adults Adverse Reactions % of Patients Rizatriptan benzoate tablets 5 mg (N=977) Rizatriptan benzoate tablets 10 mg (N=1167) Placebo (N=627) 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 tablets 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 tablets 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 tablets and reported an event divided by the total number of patients exposed to rizatriptan benzoate tablets (N=3716). 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.
Drug interactions
7.1 Propranolol The dose of rizatriptan benzoate tablets should be adjusted in propranolol-treated patients, as propranolol has been shown to increase the plasma AUC of rizatriptan by 70% [see Dosage and Administration (2.4) and Clinical Pharmacology (12.3) ] . 7.2 Ergot-Containing Drugs Ergot-containing drugs have been reported to cause prolonged vasospastic reactions. Because these effects may be additive, use of ergotamine-containing or ergot-type medications (like dihydroergotamine or methysergide) and rizatriptan benzoate tablets within 24 hours is contraindicated [see Contraindications (4) ] . 7.3 Other 5-HT 1 Agonists Because their vasospastic effects may be additive, co-administration of rizatriptan benzoate tablets and other 5-HT 1 agonists within 24 hours of each other is contraindicated [see Contraindications (4) ] . 7.4 SSRIs/SNRIs and Serotonin Syndrome Cases of serotonin syndrome have been reported during co-administration of triptans and selective serotonin reuptake inhibitors (SSRIs) or serotonin norepinephrine reuptake inhibitors (SNRIs) [see Warnings and Precautions (5.7) ] . 7.5 Monoamine Oxidase Inhibitors Rizatriptan benzoate tablets is contraindicated in patients taking MAO-A inhibitors and non-selective MAO inhibitors. A specific MAO-A inhibitor increased the systemic exposure of rizatriptan and its metabolite [see Contraindications (4) and Clinical Pharmacology (12.3) ] .
Use in specific populations
Pregnancy: Based on animal data, may cause fetal harm ( 8.1 ) 8.1 Pregnancy Risk Summary Available human data on the use of rizatriptan benzoate tablets in pregnant women are not sufficient to draw conclusions about drug-associated risk for major birth defects and miscarriage. In animal studies, developmental toxicity was observed following oral administration of rizatriptan during pregnancy (decreased fetal body weight in rats) or throughout pregnancy and lactation (increased mortality, decreased body weight, and neurobehavioral impairment in rat offspring) at maternal plasma exposures greater than that expected at therapeutic doses in humans [see Animal Data]. In the U.S. general population, the estimated background risk of major birth defects and of miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. The reported rate of major birth defects among deliveries to women with migraine range from 2.2% to 2.9% and the reported rate of miscarriage was 17%, which are similar to rates reported in women without migraine. Clinical Considerations Disease-Associated Maternal and/or Embryo/Fetal Risk In women with migraine, there is an increased risk of adverse perinatal outcomes in the mother, including pre-eclampsia and gestational hypertension. Data Human Data The Pregnancy Registry for rizatriptan benzoate tablets did not identify any pattern of congenital anomalies or other adverse birth outcomes over the period of 1998 to 2018. However, the lack of identification of any pattern should be viewed with caution, as the number of prospective reports with outcome information was low and did not provide sufficient power to detect an increased risk of individual birth defects associated with the use of rizatriptan benzoate tablets. Additionally, there was significant loss to follow- up in the prospective pregnancy reports, further complicating this assessment of an association between rizatriptan benzoate tablets and any pattern of congenital anomalies or other adverse birth outcomes. In a study using data from the Swedish Medical Birth Register, live births to women who reported using triptans or ergots during pregnancy were compared with those of women who did not. Of the 157 births with first-trimester exposure to rizatriptan, 7 infants were born with malformations (relative risk 1.01 [95% CI: 0.40 to 2.08]). A study using linked data from the Medical Birth Registry of Norway to the Norwegian Prescription Database compared pregnancy outcomes in women who redeemed prescriptions for triptans during pregnancy, as well as a migraine disease comparison group who redeemed prescriptions for triptans before pregnancy only, compared with a population control group. Of the 310 women who redeemed prescriptions for rizatriptan during the first trimester, 10 had infants with major congenital malformations (OR 1.03 [95% CI: 0.55 to 1.93]), while for the 271 women who redeemed prescriptions for rizatriptan before, but not during, pregnancy, 12 had infants with major congenital malformations (OR 1.48 [95% CI: 0.83 to 2.64]), each compared with the population comparison group. Animal Data When rizatriptan (0, 2, 10, or 100 mg/kg/day) was administered orally to pregnant rats throughout organogenesis, a decrease in fetal body weight was observed at the highest doses tested. At the mid dose (10 mg/kg/day), which was a no-effect dose for adverse effects on embryofetal development, plasma exposure (AUC) was approximately 15 times that in humans at the maximum recommended human dose (MRHD) of 30 mg/day. When rizatriptan (0, 5, 10, or 50 mg/kg/day) was administered orally to pregnant rabbits throughout organogenesis, no adverse fetal effects were observed. Plasma exposure (AUC) at the highest dose tested was 115 times that in humans at the MRHD. Placental transfer of drug to the fetus was demonstrated in both species. Oral administration of rizatriptan (0, 2, 10, or 100 mg/kg/day) to female rats prior to and during mating and continuing throughout gestation and lactation resulted in reduced body weight in offspring from birth and throughout lactation at all but the lowest dose tested (2 mg/kg/day). Plasma exposure (AUC) at the no-effect dose (2 mg/kg/day) for adverse effects on postnatal development was similar to that in humans at the MRHD. Oral administration of rizatriptan (0, 5, 100, or 250 mg/kg/day) throughout organogenesis and lactation resulted in neonatal mortality, reduced body weight (which persisted into adulthood), and impaired neurobehavioral function in offspring at all but the lowest dose tested. Plasma exposure (AUC) at the no-effect dose for adverse effects on postnatal development (5 mg/kg/day) was approximately 8 times that in humans at the MRHD. 8.2 Lactation Risk Summary There are no data on the presence of rizatriptan or any active metabolites in human milk, or on the effects of rizatriptan on the breastfed infant, or on milk production. Rizatriptan was excreted in rat milk, with levels in milk approximately 6 times those in maternal plasma. The developmental and health benefits of breastfeeding should be considered along with the mother's clinical need for rizatriptan benzoate tablets and any potential adverse effects on the breastfed infant from rizatriptan benzoate tablets from the underlying maternal condition. Data Following oral administration of rizatriptan to lactating rats at a dose of 100 mg/kg/day, drug concentrations of rizatriptan in milk samples exceeded maternal plasma drug concentrations by approximately 6-fold. 8.4 Pediatric Use Safety and effectiveness in pediatric patients under 6 years of age have not been established. The efficacy and safety of rizatriptan benzoate tablets in the acute treatment of migraine in patients aged 6 to 17 years was established in an adequate and well-controlled study [see Clinical Studies (14.2) ].
Pregnancy
8.1 Pregnancy Risk Summary Available human data on the use of rizatriptan benzoate tablets in pregnant women are not sufficient to draw conclusions about drug-associated risk for major birth defects and miscarriage. In animal studies, developmental toxicity was observed following oral administration of rizatriptan during pregnancy (decreased fetal body weight in rats) or throughout pregnancy and lactation (increased mortality, decreased body weight, and neurobehavioral impairment in rat offspring) at maternal plasma exposures greater than that expected at therapeutic doses in humans [see Animal Data]. In the U.S. general population, the estimated background risk of major birth defects and of miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively. The reported rate of major birth defects among deliveries to women with migraine range from 2.2% to 2.9% and the reported rate of miscarriage was 17%, which are similar to rates reported in women without migraine. Clinical Considerations Disease-Associated Maternal and/or Embryo/Fetal Risk In women with migraine, there is an increased risk of adverse perinatal outcomes in the mother, including pre-eclampsia and gestational hypertension. Data Human Data The Pregnancy Registry for rizatriptan benzoate tablets did not identify any pattern of congenital anomalies or other adverse birth outcomes over the period of 1998 to 2018. However, the lack of identification of any pattern should be viewed with caution, as the number of prospective reports with outcome information was low and did not provide sufficient power to detect an increased risk of individual birth defects associated with the use of rizatriptan benzoate tablets. Additionally, there was significant loss to follow- up in the prospective pregnancy reports, further complicating this assessment of an association between rizatriptan benzoate tablets and any pattern of congenital anomalies or other adverse birth outcomes. In a study using data from the Swedish Medical Birth Register, live births to women who reported using triptans or ergots during pregnancy were compared with those of women who did not. Of the 157 births with first-trimester exposure to rizatriptan, 7 infants were born with malformations (relative risk 1.01 [95% CI: 0.40 to 2.08]). A study using linked data from the Medical Birth Registry of Norway to the Norwegian Prescription Database compared pregnancy outcomes in women who redeemed prescriptions for triptans during pregnancy, as well as a migraine disease comparison group who redeemed prescriptions for triptans before pregnancy only, compared with a population control group. Of the 310 women who redeemed prescriptions for rizatriptan during the first trimester, 10 had infants with major congenital malformations (OR 1.03 [95% CI: 0.55 to 1.93]), while for the 271 women who redeemed prescriptions for rizatriptan before, but not during, pregnancy, 12 had infants with major congenital malformations (OR 1.48 [95% CI: 0.83 to 2.64]), each compared with the population comparison group. Animal Data When rizatriptan (0, 2, 10, or 100 mg/kg/day) was administered orally to pregnant rats throughout organogenesis, a decrease in fetal body weight was observed at the highest doses tested. At the mid dose (10 mg/kg/day), which was a no-effect dose for adverse effects on embryofetal development, plasma exposure (AUC) was approximately 15 times that in humans at the maximum recommended human dose (MRHD) of 30 mg/day. When rizatriptan (0, 5, 10, or 50 mg/kg/day) was administered orally to pregnant rabbits throughout organogenesis, no adverse fetal effects were observed. Plasma exposure (AUC) at the highest dose tested was 115 times that in humans at the MRHD. Placental transfer of drug to the fetus was demonstrated in both species. Oral administration of rizatriptan (0, 2, 10, or 100 mg/kg/day) to female rats prior to and during mating and continuing throughout gestation and lactation resulted in reduced body weight in offspring from birth and throughout lactation at all but the lowest dose tested (2 mg/kg/day). Plasma exposure (AUC) at the no-effect dose (2 mg/kg/day) for adverse effects on postnatal development was similar to that in humans at the MRHD. Oral administration of rizatriptan (0, 5, 100, or 250 mg/kg/day) throughout organogenesis and lactation resulted in neonatal mortality, reduced body weight (which persisted into adulthood), and impaired neurobehavioral function in offspring at all but the lowest dose tested. Plasma exposure (AUC) at the no-effect dose for adverse effects on postnatal development (5 mg/kg/day) was approximately 8 times that in humans at the MRHD.
Pediatric use
8.4 Pediatric Use Safety and effectiveness in pediatric patients under 6 years of age have not been established. The efficacy and safety of rizatriptan benzoate tablets in the acute treatment of migraine in patients aged 6 to 17 years was established in an adequate and well-controlled study [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 tablets to those who received placebo. The adverse reaction pattern in pediatric patients is expected to be similar to that in adults.
Geriatric use
8.5 Geriatric Use Clinical studies of rizatriptan benzoate tablets did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. Other reported clinical experience has not identified differences in responses between the elderly and younger patients. Although the pharmacokinetics of rizatriptan were similar in elderly (aged ≥65 years) and in younger adults (n=17), in general, dose selection for an elderly patient should be cautious, starting at the low end of the dosing range. This reflects the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. Geriatric patients who have other cardiovascular risk factors (e.g., diabetes, hypertension, smoking, obesity, strong family history of coronary artery disease) should have a cardiovascular evaluation prior to receiving rizatriptan benzoate tablets [see Warnings and Precautions (5.1) ] .
Overdosage
No overdoses of rizatriptan benzoate tablets were reported during clinical trials in adults. Some adult patients who received 40 mg of rizatriptan benzoate tablets either a single dose or as two doses with a 2-hour interdose interval had dizziness and somnolence. In a clinical pharmacology study in which 12 adult subjects received rizatriptan benzoate tablets, at total cumulative doses of 80 mg (given within four hours), two of the subjects experienced syncope, dizziness, bradycardia including third degree AV block, vomiting, and/or incontinence. In the long-term, open label study, involving 606 treated pediatric migraineurs 12 to 17 years of age (of which 432 were treated for at least 12 months), 151 patients (25%) took two 10-mg doses of rizatriptan benzoate orally disintegrating tablets within a 24- hour period. Adverse reactions for 3 of these patients included abdominal discomfort, fatigue, and dyspnea. In addition, based on the pharmacology of rizatriptan benzoate tablets, hypertension or myocardial ischemia could occur after overdosage. Gastrointestinal decontamination, (i.e., gastric lavage followed by activated charcoal) should be considered in patients suspected of an overdose with rizatriptan benzoate tablets. Clinical and electrocardiographic monitoring should be continued for at least 12 hours, even if clinical symptoms are not observed. The effects of hemo- or peritoneal dialysis on serum concentrations of rizatriptan are unknown.
Description
Rizatriptan benzoate tablets, USP contains rizatriptan benzoate, a selective 5- hydroxytryptamine 1B/1D (5-HT 1B/1D ) receptor agonist. Rizatriptan benzoate, USP is described chemically as: 1H-indole-3-ethanamine, N,N-dimethyl-5-(1H-1,2,4-triazol-1-ylmethyl)-,monobenzoate and its structural formula is: Its empirical formula is C 15 H 19 N 5
• C 7 H 6 O 2 , representing a molecular weight of the free base of 269.4. Rizatriptan benzoate, USP is a White to almost white crystalline powder that is soluble in water; sparingly soluble in alcohol, slightly soluble in methylene chloride. Rizatriptan benzoate tablets, USP are available for oral administration in strengths of 5 mg and 10 mg (corresponding to 7.265 mg or 14.530 mg of the benzoate salt, respectively). Each compressed tablet contains the following inactive ingredients: Lactose Monohydrate USP NF, Microcrystalline Cellulose USP NF, Pregelatinised Starch USP NF, Ferric Oxide USP NF and Magnesium Stearate USP NF. image
Mechanism of action
12.1 Mechanism of Action Rizatriptan binds with high affinity to human cloned 5-HT 1B/1D receptors. Rizatriptan benzoate tablets presumably exerts its therapeutic effects in the treatment of migraine headache by binding to 5-HT 1B/1D receptors located on intracranial blood vessels and sensory nerves of the trigeminal system.
How supplied
Rizatriptan benzoate tablets, USP 5 mg, are Pale pink colored, capsule shaped uncoated tablets debossed with '388' on one side and plain on other side. They are supplied as follows: NDC 82619-111-01, bottle of 30 tablets NDC 82619-111-02, bottle of 1000 tablets NDC 82619-111-04, carton of 12 tablets NDC 82619-111-05, carton of 18 tablets Rizatriptan benzoate tablets, USP 10 mg, are Pale pink colored, capsule shaped uncoated tablets debossed with '389' on one side and plain on other side. They are supplied as follows: NDC 82619-112-01, bottle of 30 tablets NDC 82619-112-02, bottle of 1000 tablets NDC 82619-112-04, carton of 12 tablets NDC 82619-112-05, carton of 18 tablets Storage Store Rizatriptan benzoate tablets at 20° to 25°C (68° to 77°F); excursions permitted between 15° and 30°C (59° and 86°F) [see USP Controlled Room Temperature].
Patient information
Advise the patient to read the FDA-approved patient labeling (Patient Information). Risk of Myocardial Ischemia and/or Infarction, Prinzmetal's Angina, Other Vasospasm- Related Events, and Cerebrovascular Events Inform patients that rizatriptan benzoate tablets, USP may cause serious cardiovascular side effects such as myocardial infarction or stroke. Although serious cardiovascular events can occur without warning symptoms, patients should be alert for the signs and symptoms of chest pain, shortness of breath, weakness, slurring of speech, and should ask for medical advice when observing any indicative sign or symptoms. Patients should be apprised of the importance of this follow-up [see Warnings and Precautions ( 5.1 , 5.2 , 5.4 , 5.5 )] . Serotonin Syndrome Patients should be cautioned about the risk of serotonin syndrome with the use of rizatriptan benzoate tablets or other triptans, particularly during combined use with selective serotonin reuptake inhibitors (SSRIs) or serotonin norepinephrine reuptake inhibitors (SNRIs) [see Warnings and Precautions (5.7) , Drug Interactions (7.4) , and Clinical Pharmacology (12.3) ] . Pregnancy Inform patients that rizatriptan benzoate tablets should not be used during pregnancy unless the potential benefit justifies the potential risk to the fetus [see Use in Specific Populations (8.1) ]. Lactation Advise patients to notify their healthcare provider if they are breastfeeding or plan to breastfeed [see Use in Specific Populations (8.2) ] Ability to Perform Complex Tasks Since migraines or treatment with rizatriptan benzoate tablets may cause somnolence and dizziness, instruct patients to evaluate their ability to perform complex tasks during migraine attacks and after administration of rizatriptan benzoate tablets, USP Medication Overuse Headache Inform patients that use of acute migraine drugs for 10 or more days per month may lead to an exacerbation of headache, and encourage patients to record headache frequency and drug use (e.g., by keeping a headache diary) [see Warnings and Precautions (5.6) ]. Manufactured by: V-Ensure Pharma Technologies Pvt. Ltd Raigad Maharashtra 410206, India Distributed by: Creekwood Pharmaceuticals LLC. Parsippany, NJ 07054 Revised: August, 2023
Label text from the FDA structured product label by Creekwood Pharmaceuticals LLC (revised Oct 9, 2025). Long sections are shortened; the complete label is on DailyMed.
Active ingredients
- Rizatriptan Benzoate in 60 products
Rizatriptan Benzoate NDC products (60)
| NDC | Strength & form | Labeler | Type |
|---|---|---|---|
| 50090-3343 | Rizatriptan Benzoate 10 mg/1 Tablet | A-S Medication Solutions | ANDA |
| 50090-3367 | Rizatriptan Benzoate 10 mg/1 Tablet | A-S Medication Solutions | ANDA |
| 80425-0535 | Rizatriptan Benzoate 10 mg/1 Tablet, Orally Disintegrating | Advanced Rx of Tennessee, LLC | ANDA |
| 67877-261 | Rizatriptan Benzoate 5 mg/1 Tablet | Ascend Laboratories, LLC | ANDA |
| 67877-262 | Rizatriptan Benzoate 10 mg/1 Tablet | Ascend Laboratories, LLC | ANDA |
| 76420-909 | Rizatriptan Benzoate 10 mg/1 Tablet, Orally Disintegrating | Asclemed USA, Inc. | ANDA |
| 76420-908 | Rizatriptan Benzoate 5 mg/1 Tablet, Orally Disintegrating | Asclemed USA, Inc. | ANDA |
| 65862-599 | Rizatriptan Benzoate 5 mg/1 Tablet | Aurobindo Pharma Limited | ANDA |
| 65862-600 | Rizatriptan Benzoate 10 mg/1 Tablet | Aurobindo Pharma Limited | ANDA |
| 65862-625 | Rizatriptan Benzoate 5 mg/1 Tablet, Orally Disintegrating | Aurobindo Pharma Limited | ANDA |
| 65862-626 | Rizatriptan Benzoate 10 mg/1 Tablet, Orally Disintegrating | Aurobindo Pharma Limited | ANDA |
| 69452-156 | Rizatriptan Benzoate 5 mg/1 Tablet, Orally Disintegrating | Bionpharma Inc., | ANDA |
| 69452-157 | Rizatriptan Benzoate 10 mg/1 Tablet, Orally Disintegrating | Bionpharma Inc., | ANDA |
| 71335-1912 | Rizatriptan Benzoate 10 mg/1 Tablet | Bryant Ranch Prepack | ANDA |
| 71335-2982 | Rizatriptan Benzoate 10 mg/1 Tablet, Orally Disintegrating | Bryant Ranch Prepack | ANDA |
| 71335-2979 | Rizatriptan Benzoate 5 mg/1 Tablet | Bryant Ranch Prepack | ANDA |
| 71335-2536 | Rizatriptan Benzoate 5 mg/1 Tablet | Bryant Ranch Prepack | ANDA |
| 71335-2031 | Rizatriptan Benzoate 5 mg/1 Tablet | Bryant Ranch Prepack | ANDA |
| 71335-1149 | Rizatriptan Benzoate 5 mg/1 Tablet | Bryant Ranch Prepack | ANDA |
| 71335-1819 | Rizatriptan Benzoate 10 mg/1 Tablet, Orally Disintegrating | Bryant Ranch Prepack | ANDA |
| 62135-999 | Rizatriptan Benzoate 10 mg/1 Tablet, Orally Disintegrating | Chartwell RX, LLC | ANDA |
| 62135-998 | Rizatriptan Benzoate 5 mg/1 Tablet, Orally Disintegrating | Chartwell RX, LLC | ANDA |
| 69097-866 | Rizatriptan Benzoate 10 mg/1 Tablet | Cipla USA Inc. | ANDA |
| 69097-865 | Rizatriptan Benzoate 5 mg/1 Tablet | Cipla USA Inc. | ANDA |
| 82619-112 | Rizatriptan Benzoate 10 mg/1 Tablet | Creekwood Pharmaceuticals LLC | ANDA |
| 82619-111 | Rizatriptan Benzoate 5 mg/1 Tablet | Creekwood Pharmaceuticals LLC | ANDA |
| 61919-394 | Rizatriptan Benzoate 5 mg/1 Tablet | DIRECT RX | ANDA |
| 72189-258 | Rizatriptan Benzoate 10 mg/1 Tablet | direct rx | ANDA |
| 72189-316 | Rizatriptan Benzoate 5 mg/1 Tablet | Direct Rx | ANDA |
| 61919-656 | Rizatriptan Benzoate 10 mg/1 Tablet | DIRECT RX | ANDA |
| 72189-447 | Rizatriptan Benzoate 10 mg/1 Tablet, Film Coated | Direct_Rx | ANDA |
| 72189-512 | Rizatriptan Benzoate 5 mg/1 Tablet | Direct_Rx | ANDA |
| 68462-468 | Rizatriptan Benzoate 10 mg/1 Tablet, Orally Disintegrating | Glenmark Pharmaceuticals Inc., USA | ANDA |
| 68462-467 | Rizatriptan Benzoate 5 mg/1 Tablet, Orally Disintegrating | Glenmark Pharmaceuticals Inc., USA | ANDA |
| 68462-466 | Rizatriptan Benzoate 10 mg/1 Tablet | Glenmark Pharmaceuticals Inc., USA | ANDA |
| 68462-465 | Rizatriptan Benzoate 5 mg/1 Tablet | Glenmark Pharmaceuticals Inc., USA | ANDA |
| 51407-681 | Rizatriptan Benzoate 5 mg/1 Tablet | Golden State Medical Supply, Inc. | ANDA |
| 51407-680 | Rizatriptan Benzoate 10 mg/1 Tablet, Orally Disintegrating | Golden State Medical Supply, Inc. | ANDA |
| 51407-679 | Rizatriptan Benzoate 5 mg/1 Tablet, Orally Disintegrating | Golden State Medical Supply, Inc. | ANDA |
| 51407-682 | Rizatriptan Benzoate 10 mg/1 Tablet | Golden State Medical Supply, Inc. | ANDA |
| 33342-094 | Rizatriptan Benzoate 10 mg/1 Tablet, Orally Disintegrating | Macleods Pharmaceuticals Limited | ANDA |
| 33342-093 | Rizatriptan Benzoate 5 mg/1 Tablet, Orally Disintegrating | Macleods Pharmaceuticals Limited | ANDA |
| 68071-3568 | Rizatriptan Benzoate 10 mg/1 Tablet, Orally Disintegrating | NuCare Pharmaceuticals,Inc. | ANDA |
| 43817-135 | Rizatriptan Benzoate 10 mg/1 Tablet, Orally Disintegrating | Panacea Biotec Limited | ANDA |
| 43817-133 | Rizatriptan Benzoate 5 mg/1 Tablet, Orally Disintegrating | Panacea Biotec Limited | ANDA |
| 82804-202 | Rizatriptan Benzoate 10 mg/1 Tablet | Proficient Rx LP | ANDA |
| 71205-644 | Rizatriptan Benzoate 10 mg/1 Tablet | Proficient Rx LP | ANDA |
| 71205-557 | Rizatriptan Benzoate 10 mg/1 Tablet, Orally Disintegrating | Proficient Rx LP | ANDA |
| 71205-398 | Rizatriptan Benzoate 10 mg/1 Tablet, Orally Disintegrating | Proficient Rx LP | ANDA |
| 70518-4362 | Rizatriptan Benzoate 10 mg/1 Tablet, Orally Disintegrating | REMEDYREPACK INC. | ANDA |
| 57237-088 | Rizatriptan Benzoate 10 mg/1 Tablet | Rising Pharma Holdings, Inc. | ANDA |
| 57237-087 | Rizatriptan Benzoate 5 mg/1 Tablet | Rising Pharma Holdings, Inc. | ANDA |
| 57237-086 | Rizatriptan Benzoate 10 mg/1 Tablet, Orally Disintegrating | Rising Pharma Holdings, Inc. | ANDA |
| 57237-085 | Rizatriptan Benzoate 5 mg/1 Tablet, Orally Disintegrating | Rising Pharma Holdings, Inc. | ANDA |
| 0093-7472 | Rizatriptan Benzoate 10 mg/1 Tablet | Teva Pharmaceuticals USA, Inc. | ANDA |
| 0093-7471 | Rizatriptan Benzoate 5 mg/1 Tablet | Teva Pharmaceuticals USA, Inc. | ANDA |
| 29300-317 | Rizatriptan Benzoate 10 mg/1 Tablet | Unichem Pharmaceuticals (USA), Inc. | ANDA |
| 29300-316 | Rizatriptan Benzoate 5 mg/1 Tablet | Unichem Pharmaceuticals (USA), Inc. | ANDA |
| 29300-269 | Rizatriptan Benzoate 10 mg/1 Tablet, Orally Disintegrating | Unichem Pharmaceuticals (USA), Inc. | ANDA |
| 29300-268 | Rizatriptan Benzoate 5 mg/1 Tablet, Orally Disintegrating | Unichem Pharmaceuticals (USA), Inc. | ANDA |
Rizatriptan Benzoate recalls
- D-0533-2025 Jul 23, 2025 · Class II · Ongoing
CGMP Deviations: detection of N-nitroso-dimethyl-rizatriptan impurity, above the FDA recommended acceptable intake limit. - D-0534-2025 Jul 23, 2025 · Class II · Ongoing
CGMP Deviations: detection of N-nitroso-dimethyl-rizatriptan impurity, above the FDA recommended acceptable intake limit. - D-0532-2024 Jun 12, 2024 · Class II · Ongoing
CGMP Deviations: N-Nitroso Desmethyl Rizatriptan Impurity results that are above the FDA acceptable limit. - D-0533-2024 Jun 12, 2024 · Class II · Ongoing
CGMP Deviations: N-Nitroso Desmethyl Rizatriptan Impurity results that are above the FDA acceptable limit. - D-0534-2024 Jun 12, 2024 · Class II · Ongoing
CGMP Deviations: N-Nitroso Desmethyl Rizatriptan Impurity results that are above the FDA acceptable limit. - D-0535-2024 Jun 12, 2024 · Class II · Ongoing
CGMP Deviations: N-Nitroso Desmethyl Rizatriptan Impurity results that are above the FDA acceptable limit. - D-0079-2022 Nov 3, 2021 · Class III · Terminated
Out-of-specification test results obtained in Organic Impurities test during analysis of controlled samples. - D-0080-2022 Nov 3, 2021 · Class III · Terminated
Out-of-specification test results obtained in Organic Impurities test during analysis of controlled samples.
Frequently asked questions
What is Rizatriptan Benzoate used for?
Rizatriptan benzoate 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 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 tablets, the diagnosis of…
What are the side effects of Rizatriptan Benzoate?
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, Throat, Neck and/or Jaw Pain/Tightness/Pressure [see Warnings and Precautions (5.3) ] . Cerebrovascular Events [see Warnings and… See the full label for the complete list.
Who makes Rizatriptan Benzoate?
Rizatriptan Benzoate is listed by 24 labelers in the FDA NDC directory, including A-S Medication Solutions, Advanced Rx of Tennessee, LLC, Ascend Laboratories, LLC, Asclemed USA, Inc..
Has Rizatriptan Benzoate been recalled?
The FDA enforcement database lists 8 recalls for Rizatriptan Benzoate, most recently D-0533-2025 (class ii): CGMP Deviations: detection of N-nitroso-dimethyl-rizatriptan impurity, above the FDA recommended acceptable intake limit.