rizatriptan 5 MG (as rizatriptan benzoate 7.265 MG) Oral Tablet
DRUG INTERACTIONS
7 7.1 Propranolol The dose of rizatriptan benzoate tablets, USP 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, USP 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 tablets, USP 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 tablets, USP 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)].
OVERDOSAGE
10 No overdoses of rizatriptan benzoate tablets, USP were reported during clinical trials in adults. Some adult patients who received 40 mg of rizatriptan benzoate tablets, USP 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, USP 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 reizatriptan 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, USP 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, USP. 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
11 Rizatriptan benzoate tablet, USP contains, 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: Its molecular formula is C15H19N5•C7H6O2, representing a molecular weight of the free base of 269.4. Rizatriptan benzoate is a white to off-white, crystalline solid that is soluble in water at about 42 mg per mL (expressed as free base) at 25°C. Rizatriptan benzoate tablets, USP are available for oral administration in strengths of 5 mg 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, pregelatinized starch (maize), and magnesium stearate. riza-Structure
CLINICAL STUDIES
14 14.1 Adults The efficacy of rizatriptan benzoate tablets, USP was established in four multicenter, randomized, placebo-controlled trials. Patients enrolled in these studies were primarily female (84%) and Caucasian (88%), with a mean age of 40 years (range of 18 to 71). Patients were instructed to treat a moderate to severe headache. Headache response, defined as a reduction of moderate or severe headache pain to no or mild headache pain, was assessed for up to 2 hours (Study 1) or up to 4 hours after dosing (Studies 2, 3 and 4). Associated symptoms of nausea, photophobia, and phonophobia and maintenance of response up to 24 hours post-dose were evaluated. A second dose of Rizatriptan Benzoate Tablets, USP was allowed 2 to 24 hours after dosing for treatment of recurrent headache in Studies 1 and 2. Additional analgesics and/or antiemetics were allowed 2 hours after initial treatment for rescue in all four studies. In all studies, the percentage of patients achieving headache response 2 hours after treatment was significantly greater in patients who received either rizatriptan benzoate tablets, USP 5 mg or 10 mg compared to those who received placebo. In a separate study, doses of 2.5 mg were not different from placebo. Doses greater than 10 mg were associated with an increased incidence of adverse effects. The results from the four controlled studies are summarized in Table 2. Table 2: Response Rates 2 Hours Following Treatment of Initial Headache in Studies 1, 2, 3, and 4 *p-value <0.05 in comparison with placebo †p-value <0.05 in comparison with 5 mg ‡Results for initial headache only. Study Placebo Rizatriptan Benzoate Tablets, USP 5 mg Rizatriptan Benzoate Tablets, USP 10 mg 1 35% (n=304) 62%* (n=458) 71%*,† (n=456) 2‡ 37% (n=82) — 77%* (n=320) 3 23% (n=80) 63%* (n=352) — 4 40% (n=159) 60%* (n=164) 67%* (n=385) Comparisons of drug performance based upon results obtained in different clinical trials may not be reliable. Because studies are conducted at different times, with different samples of patients, by different investigators, employing different criteria and/or different interpretations of the same criteria, under different conditions (dose, dosing regimen, etc.), quantitative estimates of treatment response and the timing of response may be expected to vary considerably from study to study. The estimated probability of achieving an initial headache response within 2 hours following treatment in pooled Studies 1, 2, 3, and 4 is depicted in Figure 1. Figure 1: Estimated Probability of Achieving an Initial Headache Response by 2 Hours in Pooled Studies 1, 2, 3, and 4†† ††Figure 1 shows the Kaplan-Meier plot of the probability over time of obtaining headache response (no or mild pain) following treatment with rizatriptan benzoate tablets, USP or placebo. The averages displayed are based on pooled data from 4 placebo-controlled, outpatient trials providing evidence of efficacy (Studies 1, 2, 3, and 4). Patients taking additional treatment or not achieving headache response prior to 2 hours were censored at 2 hours. For patients with migraine-associated photophobia, phonophobia, and nausea at baseline, there was a decreased incidence of these symptoms following administration of rizatriptan benzoate tablets, USP compared to placebo. Two to 24 hours following the initial dose of study treatment, patients were allowed to use additional treatment for pain response in the form of a second dose of study treatment or other medication. The estimated probability of patients taking a second dose or other medication for migraine over the 24 hours following the initial dose of study treatment is summarized in Figure 2. Figure 2: Estimated Probability of Patients Taking a Second Dose of Rizatriptan benzoate tablets, USP or Other Medication for Migraines Over the 24 Hours Following the Initial Dose of Study Treatment in Pooled Studies 1, 2, 3, and 4††† †††This Kaplan-Meier plot is based on data obtained in 4 placebo-controlled outpatient clinical trials (Studies 1, 2, 3, and 4). Patients not using additional treatments were censored at 24 hours. The plot includes both patients who had headache response at 2 hours and those who had no response to the initial dose. Remedication was not allowed within 2 hours post- dose. Efficacy was unaffected by the presence of aura; by the gender, or age of the patient; or by concomitant use of common migraine prophylactic drugs (e.g., beta-blockers, calcium channel blockers, tricyclic antidepressants) or oral contraceptives. In two additional similar studies, efficacy was unaffected by relationship to menses. There were insufficient data to assess the impact of race on efficacy. riza-Fig-1 riza-Fig-2 14.2 Pediatric Patients 6 to 17 Years of Age The efficacy of rizatriptan benzoate orally disintegrating tablets in pediatric patients 6 to 17 years was evaluated in a multicenter, randomized, double-blind, placebo-controlled, parallel group clinical trial (Study 7). Patients had to have at least a 6-month history of migraine attacks (with or without aura) usually lasting 3 hours or more (when untreated). The patient population was historically non-responsive to NSAIDs and acetaminophen therapy. Patients were instructed to treat a single migraine attack with headache pain of moderate to severe intensity. The treatment phase of the study had two stages. Stage 1 was used to identify placebo nonresponders, who then entered into Stage 2, in which patients were randomized to rizatriptan benzoate or placebo. Using a weight-based dosing strategy, patients 20 kg to <40 kg (44 lb to <88 lb) received rizatriptan benzoate orally disintegrating tablets 5 mg or placebo, and patients ≥40 kg (88 lb) received rizatriptan benzoate orally disintegrating tablets10 mg or placebo. The mean age for the studied patient population was 13 years. Sixty-one percent of the patients were Caucasian, and fifty-six percent of the patients were female. The percentage of patients achieving the primary efficacy endpoint of no headache pain at 2 hours after treatment was significantly greater in patients who received rizatriptan benzoate orally disintegrating tablets, compared with those who received placebo (33% vs. 24%). Study 7 results are summarized in Table 4. Table 4: Response Rates 2 Hours Following Treatment of Initial Headache in Pediatric Patients 6 to 17 Years of Age in Study 7 Endpoint Placebo Rizatriptan benzoate orally disintegrating tablets p-Value No headache pain at 2 hours post-dose 24% (n/m=94/388) 33% (n/m=126/382) 0.01 n = Number of evaluable patients with no headache pain at 2 hours post-dose. m = Number of evaluable patients in population. The observed percentage of pediatric patients achieving no headache pain within 2 hours following initial treatment with rizatriptan benzoate orally disintegrating tablets is shown in Figure 5. Figure 5: Observed Percentage of Patients Reporting No Headache Pain by 2 Hours Post-Dose in Study 7 The prevalence of the exploratory endpoints of absence of migraine-associated symptoms (nausea, photophobia, and phonophobia) at 2 hours after taking the dose was not statistically significantly different between patients who received rizatriptan benzoate orally disintegrating tablets and those who received placebo. riza-Fig-3
HOW SUPPLIED
16 /STORAGE AND HANDLING Rizatriptan benzoate tablets, USP 5 mg, are white to off-white, capsule-shaped, compressed tablets debossed “RZT” on one side and “5” on other side. They are supplied as follows: NDC 67877-261-30, bottle of 30 tablets. NDC 67877-261-01, bottle of 100 tablets. NDC 67877-261-05, bottle of 500 tablets. NDC 67877-261-18, carton of 18 tablets. NDC 67877-261-25, carton of 12 tablets Rizatriptan benzoate tablets, USP 10 mg, are white to off-white, capsule-shaped, compressed tablets debossed “RZT” on one side and “10” on other side. They are supplied as follows: NDC 67877-262-30, bottle of 30 tablets. NDC 67877-262-01, bottle of 100 tablets. NDC 67877-262-05, bottle of 500 tablets. NDC 67877-262-18, carton of 18 tablets. NDC 67877-262-25, carton of 12 tablets Storage Store rizatriptan benzoate tablets, USP at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature]. Dispense in a tight, light-resistant container as defined in the USP using a child-resistant closure.
GERIATRIC USE
8.5 Geriatric Use Clinical studies of rizatriptan benzoate tablets, USP 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, USP [see Warnings and Precautions (5.1)].
DOSAGE FORMS AND STRENGTHS
3 Rizatriptan benzoate tablets, USP 5 mg tablets are white to off-white, capsule-shaped, compressed tablets debossed “RZT” on one side and “5” on other side. 10 mg tablets are white to off-white, capsule-shaped, compressed tablets debossed “RZT” on one side and “10” on other side. Rizatriptan Benzoate Tablets, USP : 5 mg and 10 mg (3)
MECHANISM OF ACTION
12.1 Mechanism of Action Rizatriptan binds with high affinity to human cloned 5-HT1B/1D receptors. Rizatriptan benzoate tablets, USP presumably exerts its therapeutic effects in the treatment of migraine headache by binding to 5-HT1B/1D receptors located on intracranial blood vessels and sensory nerves of the trigeminal system.
INDICATIONS AND USAGE
1 Rizatriptan benzoate tablets, USP 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, USP 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, USP the diagnosis of migraine should be reconsidered before rizatriptan benzoate tablets, USP is administered to treat any subsequent attacks. Rizatriptan benzoate tablets, USP is not indicated for use in the management of hemiplegic or basilar migraine [see Contraindications (4)]. Rizatriptan benzoate tablets, USP is not indicated for the prevention of migraine attacks. Safety and effectiveness of rizatriptan benzoate tablets, USP have not been established for cluster headache. Rizatriptan benzoate tablets, USP 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)
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, USP 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, USP to those who received placebo. The adverse reaction pattern in pediatric patients is expected to be similar to that in adults.
PREGNANCY
8.1 Pregnancy Pregnancy Category C There are no adequate and well-controlled studies in pregnant women. Rizatriptan benzoate tablets, USP should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. In a general reproductive study in rats, birth weights and pre- and post-weaning weight gain were reduced in the offspring of females treated prior to and during mating and throughout gestation and lactation with doses of 10 and 100 mg/kg/day. In a pre- and post-natal developmental toxicity study in rats, an increase in mortality of the offspring at birth and for the first three days after birth, a decrease in pre- and post-weaning weight gain, and decreased performance in a passive avoidance test (which indicates a decrease in learning capacity of the offspring) were observed at doses of 100 and 250 mg/kg/day. The no-effect dose for all of these effects was 5 mg/kg/day, associated with a maternal plasma exposure (AUC) approximately 7.5 times that in humans receiving the MRDD. With doses of 100 and 250 mg/kg/day, the decreases in average weight of both the male and female offspring persisted into adulthood. All effects on the offspring in both studies occurred in the absence of any apparent maternal toxicity. In embryofetal development studies, no teratogenic effects were observed when pregnant rats and rabbits were administered doses of 100 and 50 mg/kg/day, respectively, during organogenesis. Fetal weights were decreased in conjunction with decreased maternal weight gain at the highest doses tested. The developmental no-effect dose in these studies was 10 mg/kg/day in both rats and rabbits (maternal exposures approximately 15 times human exposure at the MRDD). Toxicokinetic studies demonstrated placental transfer of drug in both species.
NUSRING MOTHERS
8.3 Nursing Mothers It is not known whether this drug is excreted in human milk. Because many drugs are excreted in human milk, caution should be exercised when rizatriptan benzoate tablets, USP is administered to a nursing woman. Rizatriptan is extensively excreted in rat milk, with levels in milk at least 5-fold higher than levels in maternal plasma.
WARNING AND CAUTIONS
5 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, USP 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, USP. Some of these reactions occurred in patients without known coronary artery disease (CAD). 5-HT1 agonists including rizatriptan benzoate tablets, USP 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, USP. If there is evidence of CAD or coronary artery vasospasm, rizatriptan benzoate tablets, USP 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, USP dose in a medically- supervised setting and performing an electrocardiogram (ECG) immediately following rizatriptan benzoate tablets, USP administration. Periodic cardiovascular evaluation should be considered in intermittent long-term users of rizatriptan benzoate tablets, USP 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 tablets, USP 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, USP 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 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, USP 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 tablets, USP 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 tablets, USP 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 tablets, USP 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 tablets, USP 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 tablets, USP. In healthy young adult male and female patients who received maximal doses of rizatriptan benzoate tablets, USP (10 mg every 2 hours for 3 doses), slight increases in blood pressure (approximately 2-3 mmHg) were observed. Rizatriptan benzoate tablets, USP is contraindicated in patients with uncontrolled hypertension [see Contraindications (4)].
INFORMATION FOR PATIENTS
17 PATIENT COUNSELING INFORMATION See 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, USP 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, USP should not be used during pregnancy unless the potential benefit justifies the potential risk to the fetus [see Use in Specific Populations (8.1)]. Nursing Mothers Advise patients to notify their healthcare provider if they are breastfeeding or plan to breastfeed [see Use in Specific Populations (8.3)]. Ability To Perform Complex Tasks Since migraines or treatment with rizatriptan benzoate tablets, USP 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 in India by: Alkem Laboratories Limited H.O.: ALKEM HOUSE, Senapati Bapat Marg, Lower Parel, Mumbai – 400 013, INDIA Distributed by: Ascend Laboratories, LLC, Montvale, NJ 07645 Revised: 03/2016 Patient Information RIZATRIPTAN BENZOATE TABLETS, USP 5 mg and 10 mg Read this Patient Information before you start taking rizatriptan benzoate tablets, USP and each time you get a refill. There may be new information. This information does not take the place of talking to your doctor about your medical condition or your treatment. Unless otherwise stated, the information in this Patient Information leaflet applies to both rizatriptan benzoate tablets, USP and to rizatriptan benzoate orally disintegrating tablets What is rizatriptan benzoate, USP ? Rizatriptan benzoate tablets, USP is a prescription medicine that belongs to a class of medicines called Triptans. Rizatriptan benzoate tablets, USP is available as a traditional tablet and as an orally disintegrating tablet. Rizatriptan benzoate tablet, USP are used to treat migraine attacks with or without aura in adults and in children 6 to 17 years of age. Rizatriptan benzoate tablets, USP is not to be used to prevent migraine attacks. Rizatriptan benzoate tablets, USP is not for the treatment of hemiplegic or basilar migraines. It is not known if rizatriptan benzoate tablets, USP is safe and effective for the treatment of cluster headaches. It is not known if taking more than 1 dose of rizatriptan benzoate tablet, USP in 24 hours is safe and effective in children 6 to 17 years of age. It is not known if rizatriptan benzoate tablet, USP is safe and effective in children under 6 years of age. Who should not take rizatriptan benzoate tablets, USP? Do not take rizatriptan benzoate tablets, USP if you: have or have had heart problems have or have had a stroke or a transient ischemic attack (TIA) have or have had blood vessel problems including ischemic bowel disease have uncontrolled high blood pressure have taken other Triptan medicines in the last 24 hours have taken ergot-containing medicines in the last 24 hours have hemiplegic or basilar migraines take monoamine oxidase (MAO) inhibitor or have taken a MAO inhibitor within the last 2 weeks are allergic to rizatriptan benzoate, USP or any of the ingredients in Rizatriptan Benzoate Tablets, USP. See the end of this leaflet for a complete list of ingredients in Rizatriptan Benzoate Tablets, USP. Talk to your doctor before taking this medicine if you have any of the conditions listed above or if you are not sure if you take any of these medicines. What should I tell my doctor before taking rizatriptan benzoate tablets, USP? Before you take rizatriptan benzoate tablets,, USP tell your doctor if you: have or have had heart problems, high blood pressure, chest pain, or shortness of breath have any risk factors for heart problems or blood vessel problems such as: high blood pressure high cholesterol smoking obesity diabetes family history of heart problems you are post menopausal you are a male over 40 have kidney or liver problems have any other medical condition are pregnant or plan to become pregnant. It is not known if rizatriptan benzoate tablets, USP will harm your unborn baby. If you become pregnant while taking rizatriptan benzoate tablets, USP talk to your healthcare provider are breastfeeding or plan to breastfeed. It is not known if rizatriptan benzoate tablets, USP passes into your breast milk. Talk to your doctor about the best way to feed your baby if you take rizatriptan benzoate tablets, USP. Tell your doctor about all the medicines you take, including prescription and nonprescription medicines, vitamins, and herbal supplements. Rizatriptan benzoate tablets, USP and other medicines may affect each other causing side effects. Rizatriptan benzoate tablets, USP may affect the way other medicines work, and other medicines may affect how rizatriptan benzoate tablets, USP works. Especially tell your doctor if you take: propranolol containing medicines such as Inderal®, Inderal® LA, or Innopran® XL medicines used to treat mood disorders, including selective serotonin reuptake inhibitors (SSRIs) or serotonin norepinephrine reuptake inhibitors (SNRIs). Ask your doctor or pharmacist for a list of these medicines, if you are not sure. Know the medicines you take. Keep a list of them to show your doctor and pharmacist when you get a new medicine. How should I take rizatriptan benzoate tablets, USP? Take rizatriptan benzoate tablets, USP exactly as your doctor tells you to take it. Your doctor will tell you how much rizatriptan benzoate tablets, USP to take and when to take it. If your headache comes back after your first rizatriptan benzoate tablets, USP dose: For adults: a second dose may be taken 2 hours after the first dose. Do not take more than 30 mg of rizatriptan benzoate tablets, USP in a 24-hour period (for example, do not take more than 3 10 mg tablets in a 24-hour period). For children 6 to 17 years of age: It is not known if taking more than 1 dose of rizatriptan benzoate tablets, USP in 24 hours is safe and effective. Talk to your doctor about what to do if your headache does not go away or comes back. If you take too much rizatriptan benzoate tablets, USP call your doctor or go to the nearest hospital emergency room right away. What should I avoid while taking rizatriptan benzoate tablets, USP? Rizatriptan benzoate tablets, USP may cause dizziness, weakness, or fainting. If you have these symptoms, do not drive a car, use machinery, or do anything that needs you to be alert. What are the possible side effects of rizatriptan benzoate tablets, USP? Rizatriptan benzoate tablets, USP may cause serious side effects. Call your doctor or go to the nearest hospital emergency room right away if you think you are having any of the serious side effects of rizatriptan benzoate tablets, USP including: heart attack. Symptoms of a heart attack may include: chest discomfort in the center of your chest that lasts for more than a few minutes or that goes away and comes back chest discomfort that feels like uncomfortable pressure, squeezing, fullness or pain pain or discomfort in your arms, back, neck, jaw or stomach shortness of breath with or without chest discomfort breaking out in a cold sweat nausea or vomiting feeling lightheaded stroke. Symptoms of a stroke may include the following sudden symptoms: numbness or weakness in your face, arm or leg, especially on one side of your body confusion, problems speaking or understanding problems seeing in 1 or both of your eyes problems walking, dizziness, loss of balance or coordination severe headache with no known cause blood vessel problems. Symptoms of blood vessel problems may include: stomach pain bloody diarrhea vision problems coldness and numbness of hands and feet serotonin syndrome. A condition called serotonin syndrome can happen when Triptan medicines such as rizatriptan benzoate tablets, USP are taken with certain other medicines. Symptoms of serotonin syndrome may include: agitation hallucinations coma fast heartbeat fast changes in your blood pressure increased body temperature muscle spasm loss of coordination nausea, vomiting or diarrhea increased blood pressure The most common side effects of rizatriptan benzoate tablets, USP in adults include: feeling sleepy or tired pain or pressure in your chest ot throat dizziness Tell your doctor if you have any side effect that bothers you or that does not go away. If you take rizatriptan benzoate tablets, USP too often, this may result in you getting chronic headaches. In such cases, you should contact your doctor, as you may have to stop taking rizatriptan benzoate tablets, USP. These are not all the possible side effects of rizatriptan benzoate tablets, USP. For more information, ask your doctor or pharmacist. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088. How should I store rizatriptan benzoate tablets, USP? Store rizatriptan benzoate tablets, USP at 20° to 25°C (68° to 77°F) [see USP Controlled Room Temperature]. Safely throw away medicine that is out of date or no longer needed. Keep rizatriptan benzoate tablets, USP and all medicines out of the reach of children. General Information about the safe and effective use of rizatriptan benzoate tablets, USP. Medicines are sometimes prescribed for purposes other than those listed in a Patient Information leaflet. Do not use rizatriptan benzoate tablets, USP for a condition for which it was not prescribed. Do not give rizatriptan benzoate tablets, USP to other people, even if they have the same symptoms that you have. It may harm them. T|his Patient Information leaflet summarizes the most important information about rizatriptan benzoate tablets, USP. If you would like more information, talk to your doctor. You can ask your pharmacist or doctor for information about rizatriptan benzoate tablets, USP that is written for health professionals. For more information contact Ascend Laboratories, LLC at 1-877-ASC-RX01 (877-272-7901 What are the ingredients in rizatriptan benzoate tablets, USP? Active ingredient in rizatriptan benzoate tablets, USP: rizatriptan benzoate. Inactive ingredients in rizatriptan benzoate tablets, USP: lactose monohydrate, microcrystalline cellulose, pregelatinized starch (maize), and magnesium stearate. Proprietary names mentioned in this leaflet are trademarks of their owners. This Patient Information has been approved by the U.S. Food and Drug Administration. Manufactured in India by: Alkem Laboratories Limited H.O.: ALKEM HOUSE, Senapati Bapat Marg, Lower Parel, Mumbai – 400 013, INDIA Distributed by: Ascend Laboratories, LLC, Montvale, NJ 07645 Revised: 03/2016
DOSAGE AND ADMINISTRATION
2 Adults: 5 mg 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 < 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, USP 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) Dosing in pediatric patients is based on the patient's body weight. The recommended dose of rizatriptan benzoate tablets, USP 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 tablets, USP 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, USP 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 For pediatric patients weighing 40 kg (88 lb) or more, taking propranolol, only a single 5 mg dose of rizatriptan benzoate tablets, USP is recommended (maximum dose of 5 mg in a 24-hour period). Rizatriptan benzoate tablets, USP 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)].