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 ) 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.
Contraindications
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 ) 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 )] .
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 )
5.1Myocardial Ischemia, Myocardial Infarction, and Prinzmetals Angina
Keep rizatriptan benzoate orally disintegrating tablets and all medicines out of the reach of children. General Information about the safe and effective use of rizatriptan benzoate orally disintegrating tablets. Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use rizatriptan benzoate for a condition for which it was not prescribed. Do not give rizatriptan benzoate orally disintegrating tablets to other people, even if they have the same symptoms that you have.
It may harm them. This Patient Information leaflet summarizes the most important information about rizatriptan benzoate orally disintegrating tablets. If you would like more information, talk to your doctor. You can ask your pharmacist or doctor for information about rizatriptan benzoate orally disintegrating tablets that is written for health professionals. For more information, call Unichem Pharmaceuticals (USA), Inc. at 1-866-562-4616 What are the ingredients in rizatriptan benzoate orally disintegrating tablets?
Active ingredient in rizatriptan benzoate orally disintegrating tablets: rizatriptan benzoate. Inactive ingredients in rizatriptan benzoate orally disintegrating tablets: colloidal silicon dioxide, crospovidone, magnesium stearate, mannitol, microcrystalline cellulose, orange flavor, sucralose. * The brand names mentioned are registered trademarks of their respective manufacturers. This Patient Information has been approved by the U.S.
Food and Drug Administration. Additional patient information leaflets can be obtained by calling Unichem at 1-866-562-4616. Manufactured by: UNICHEM LABORATORIES LTD. Pilerne Ind. Estate, Pilerne, Bardez, Goa – 403 511, India Manufactured for:
5.2Arrhythmias
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 if these disturbances occur.
5.3Chest, 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 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.
5.4Cerebrovascular Events
Cerebral hemorrhage, subarachnoid hemorrhage, and stroke have occurred in patients treated with 5-HT 1 agonists, and some have resulted in fatalities. In a number of cases, it appears possible that the cerebrovascular events were primary, the 5-HT 1 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 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 should not be administered to patients with a history of stroke or transient ischemic attack [see Contraindications ( 4 )] .
5.5Other Vasospasm Reactions 5-HT
1 agonists, including rizatriptan benzoate, 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 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
5.6Medication 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.
5.7Serotonin Syndrome
Serotonin syndrome may occur with triptans, including rizatriptan benzoate 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 )] . Serotonin syndrome symptoms may include mental status changes (e.g., agitation, hallucinations, coma), autonomic instability (e.g., tachycardia, labile blood pressure, hyperthermia), neuromuscular aberrations (e.g., hyperreflexia, incoordination) and/or gastrointestinal symptoms (e.g., nausea, vomiting, diarrhea).
The onset of symptoms can occur within minutes to hours of receiving a new or a greater dose of a serotonergic medication. Rizatriptan benzoate treatment should be discontinued if serotonin syndrome is suspected [see Drug Interactions ( 7.4 ) and Patient Counseling Information ( 17 )] .
5.8Increase in Blood Pressure
Significant elevation in blood pressure, including hypertensive crisis with acute impairment of organ systems, has been reported on rare occasions in patients with and without a history of hypertension receiving 5-HT 1 agonists, including rizatriptan benzoate. In healthy young adult male and female patients who received maximal doses of rizatriptan benzoate (10 mg every 2 hours for 3 doses), slight increases in blood pressure (approximately 2-3 mmHg) were observed.
Rizatriptan benzoate is contraindicated in patients with uncontrolled hypertension [see Contraindications ( 4 )] .
Interactions
7.1Propranolol
The dose of rizatriptan benzoate 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 )] .
7.2Ergot-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 within 24 hours is contraindicated [see Contraindications ( 4 )] .
7.3Other 5-HT1 Agonists
Because their vasospastic effects may be additive, co-administration of rizatriptan benzoate and other 5-HT 1 agonists within 24 hours of each other is contraindicated [see Contraindications ( 4 )] .
7.4SSRIs/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 )] .
7.5Monoamine Oxidase Inhibitors
Rizatriptan benzoate 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 )] .
Pregnancy and breastfeeding
8.1Pregnancy Risk Summary
Available human data on the use of rizatriptan benzoate 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 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.
Additionally, there was significant loss to follow-up in the prospective pregnancy reports, further complicating this assessment of an association between rizatriptan 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.
Adverse reactions
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 Unichem Pharmaceuticals (USA) Inc. at 1-866-562-4616 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 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 )] .
6.1Clinical 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 3700 adult patients who received single or multiple doses of rizatriptan benzoate tablets.
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 related. 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 Tablets or Placebo in Adults % of Patients Rizatriptan Rizatriptan Adverse Reactions Benzoate Tablets, Benzoate Tablets, 5 mg 10 mg Placebo (N=977) (N=1167) (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 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=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. Pediatric Patients 6 to 17 Years of Age Incidence in Controlled Clinical Trials in Pediatric Patients Adverse reactions to rizatriptan benzoate orally disintegrating tablets 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 orally disintegrating tablets 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 orally disintegrating tablets 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 orally disintegrating 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 pediatric patients 6 to 17 years of age who used Rizatriptan benzoate orally disintegrating tablets and reported an event divided by the total number of patients exposed to Rizatriptan benzoate orally disintegrating tablets (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.
6.2Postmarketing Experience
The following sect
Our copy of this section ends here. The full text is in the official label at the FDA. Open Drugs@FDA
Composition
Active ingredients
RIZATRIPTAN BENZOATE EQ 5MG BASE
Strengths and forms
The FDA lists each strength of a product separately; these pages share one label.
Prognia shows this product information for reference and learning. It is not treatment advice and can lag behind the official text. Always check the current product information and local protocols before prescribing.
