Drug Facts
Composition & Profile
Identifiers & Packaging
NDC 72189-0126-18 is as follows Rizatriptan benzoate tablets 5 mg, are pale pink to pink colored biconvex, capsule-shaped, uncoated tablets debossed with '414' on one side and 'C' on other side. Rizatriptan benzoate tablets 10 mg, are pale pink to pink colored biconvex, capsule-shaped, uncoated tablets debossed with '415' on one side and 'C' on other side. NDC 72189-0258-12 is as follows Rizatriptan Benzoate Tablets USP, 5 mg are a pale pink-colored, circular, flat, beveled-edge uncoated tablets debossed with ‘X’ on one side and ‘13’ on other side. The tablets may be mottled. Rizatriptan Benzoate Tablets USP, 10 mg are a pale pink-colored, circular, flat, beveled-edge uncoated tablets debossed with ‘X’ on one side and ‘14’ on other side. The tablets may be mottled. Storage Store rizatriptan benzoate tablets at 20°C -25°C (68°F -77°F); excursions permitted to 15°C -30°C (59°F-86°F). [See USP Controlled Room Temperature]; 126; 258; 72189-258-18
- NDC 72189-0126-18 is as follows Rizatriptan benzoate tablets 5 mg, are pale pink to pink colored biconvex, capsule-shaped, uncoated tablets debossed with '414' on one side and 'C' on other side. Rizatriptan benzoate tablets 10 mg, are pale pink to pink colored biconvex, capsule-shaped, uncoated tablets debossed with '415' on one side and 'C' on other side. NDC 72189-0258-12 is as follows Rizatriptan Benzoate Tablets USP, 5 mg are a pale pink-colored, circular, flat, beveled-edge uncoated tablets debossed with ‘X’ on one side and ‘13’ on other side. The tablets may be mottled. Rizatriptan Benzoate Tablets USP, 10 mg are a pale pink-colored, circular, flat, beveled-edge uncoated tablets debossed with ‘X’ on one side and ‘14’ on other side. The tablets may be mottled. Storage Store rizatriptan benzoate tablets at 20°C -25°C (68°F -77°F); excursions permitted to 15°C -30°C (59°F-86°F). [See USP Controlled Room Temperature]
- 126
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- 72189-258-18
Overview
Rizatriptan benzoate tablets contains rizatriptan benzoate USP, a selective 5-hydroxytryptamine1B/1D (5-HT1B/1D) receptor agonist. Rizatriptan benzoate USP is described chemically as: N,N-dimethyl-5-(1H-1,2,4-triazol-1-ylmethyl)-1H-indole-3-ethanamine monobenzoate and its structural formula is: [Structure] Its molecular formula is C15H19N5•C7H6O2, 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 and methanol, slightly soluble in isopropyl alcohol. Rizatriptan benzoate tablets are available for oral administration in strengths of 5 and 10 mg (corresponding to 7.265 mg or 14.53 mg of the benzoate salt, respectively). Each compressed tablet contains the following inactive ingredients: lactose monohydrate, microcrystalline cellulose, maize starch, ferric oxide (red), and magnesium stearate.
Indications & Usage
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. Information related to usage of rizatriptan benzoate in pediatric patients (6 to 17 years old) is approved for Merck & Co., Inc.’s Rizatriptan Benzoate Tablets. However, due to Merck & Co., Inc.’s marketing exclusivity rights, this drug product is not labeled with that pediatric patient (6 to 17 years old) usage information. 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, the diagnosis of migraine should be reconsidered before rizatriptan benzoate tablet is 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.
Dosage & Administration
1 Dosing Information in Adults The recommended starting dose of rizatriptan benzoate tablets is 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) Information related to dosage of rizatriptan benzoate in pediatric patients (6 to 17 years old) is approved for Merck & Co., Inc.’s Rizatriptan Benzoate Tablets. However, due to Merck & Co., Inc.’s marketing exclusivity rights, this drug product is not labeled with that dosage information. 2.4 Dosage Adjustment for Patients on Propranolol Adult Patients In adult patients taking propranolol, only the 5 mg dose of rizatriptan benzoate tablet is 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 Dosage adjustment information of rizatriptan benzoate for pediatric patients (6 to 17 years old) taking propranolol is approved for Merck & Co., Inc.’s Rizatriptan Benzoate Tablets. However, due to Merck & Co., Inc.’s marketing exclusivity rights, this drug product is not labeled with that dosage adjustment information.
Warnings & Precautions
1 Myocardial Ischemia, Myocardial Infarction, and Prinzmetal's Angina Rizatriptan benzoate 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. Some of these reactions occurred in patients without known coronary artery disease (CAD). 5-HT1 agonists including rizatriptan benzoate 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. If there is evidence of CAD or coronary artery vasospasm, rizatriptan benzoate 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 dose in a medically-supervised setting and performing an electrocardiogram (ECG) immediately following rizatriptan benzoate administration. Periodic cardiovascular evaluation should be considered in intermittent long-term users of rizatriptan benzoate 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-HT1 agonists. Discontinue rizatriptan benzoate if these disturbances occur. 5.3 Chest, Throat, Neck and/or Jaw Pain/Tightness/Pressure As with other 5-HT1 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-HT1 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 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)]. 5.5 Other Vasospasm Reactions 5-HT1 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-HT1 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-HT1 agonists. Since visual disorders may be part of a migraine attack, a causal relationship between these events and the use of 5-HT1 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 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)]. 5.8 Increase 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-HT1 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)].
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-HT1 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. 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 benzoate tablets or rizatriptan benzoate orally disintegrating tablets (angioedema and anaphylaxis seen) [see ADVERSE REACTIONS (6.2)].
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)]. 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 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 Adverse Reactions Rizatriptan Benzoate 5 mg Rizatriptan Benzoate 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 Information relating to adverse reactions to rizatriptan benzoate orally disintegrating tablets in a controlled clinical trial is approved for Merck & Co., Inc.’s Rizatriptan Benzoate Orally Disintegrating Tablets in pediatric patients (6 to 17 years old). However, due to Merck & Co., Inc.’s marketing exclusivity rights, this drug product is not labeled with that information. 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 postmarketing 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.
Drug Interactions
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-HT1 Agonists Because their vasospastic effects may be additive, co-administration of rizatriptan benzoate and other 5-HT1 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 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)].
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