Rizalt Tablets

/ MSD

In controlled clinical trials, single doses of 5 and 10 mg of RIZALT Tablets or RIZALT-RPD were effective for the acute treatment of migraines in adults. There is evidence that the 10-mg dose may provide a greater effect than the 5-mg dose. Individuals may vary in response to doses of RIZALT Tablets. The choice of dose should therefore be made on an individual basis, weighing the possible benefit of the 10-mg dose with the potential risk for increased adverse events. Redosing: Doses should be separated by at least 2 hours; no more than 30 mg should be taken in any 24-hour period. The safety of treating, on average, more than four headaches in a 30-day period has not been established. Patients receiving propranolol: In patients receiving propranolol, the 5-mg dose should be used, up to a maximum of 3 doses in any 24-hour period. For RIZALT-RPD Orally Disintegrating Tablets, administration with liquid is not necessary. The orally disintegrating tablet is packaged in a blister within an outer aluminum pouch. Patients should be instructed not to remove the blister from the outer pouch until just prior to dosing. The blister pack should then be peeled open with dry hands and the orally disintegrating tablet placed on the tongue, where it will dissolve and be swallowed with the saliva.

Acute treatment of migraine with/without aura in adults.

Hypersensitivity, within 24 hours of treatment with another 5-HT1 agonist or ergotamine-containg ergo-type medicdbation or methysergide, hemiplegic or basal migraine, concurrent administration with MAOI or within 2 weeks of discontinued therapy.

General: As with other 5-HT1B/1D agonists, sensations of tightness, pain, pressure, and heaviness have been reported after treatment with this product in the precordium, throat, neck and jaw. These events have not been associated with arrhythmias or definite ischemic ECG changes in clinical trials (one patient experienced chest pain with possible ischemic ECG changes). Because drugs in this class may cause coronary artery vasospasm, patients who experience signs or symptoms suggestive of angina following dosing should be evaluated for the presence of CAD or a predisposition to Prinzmetal’s variant angina before receiving additional doses of medication, and should be monitored electrocardiographically if dosing is resumed and similar symptoms recur. Similarly, patients who experience other symptoms or signs suggestive of decreased arterial flow, such as ischemic bowel syndrome or Raynaud’s syndrome following the use of any 5-HT1 agonist are candidates for further evaluation. Rizatriptan should also be administered with caution to patients with diseases that may alter the absorption, metabolism, or excretion of drugs.
Renally Impaired Patients: Rizatriptan should be used with caution in dialysis patients due to a decrease in the clearance of rizatriptan.
Hepatically Impaired Patients: Rizatriptan should be used with caution in patients with moderate hepatic insufficiency due to an increase in plasma concentrations of approximately 30%. For a given attack, if a patient has no response to the first dose of rizatriptan, the diagnosis of migraine should be reconsidered before administration of a second dose. Binding to Melanin-Containing Tissues The propensity for rizatriptan to bind melanin has not been investigated. Based on its chemical properties, rizatriptan may bind to melanin and accumulate in melanin rich tissue (e.g., eye) over time. This raises the possibility that rizatriptan could cause toxicity in these tissues after extended use. There were, however, no adverse ophthalmologic changes related to treatment with rizatriptan in the one year dog toxicity study. Although no systematic monitoring of ophthalmologic function was undertaken in clinical trials, and no specific recommendations for ophthalmologic monitoring are offered, prescribers should be aware of the possibility of long-term ophthalmologic effects. Phenylketonurics Phenylketonuric patients should be informed that RIZALT-RPD Orally Disintegrating Tablets contain phenylalanine (a component of aspartame). Each 5-mg orally disintegrating tablet contains 1.05 mg phenylalanine, and each 10-mg orally disintegrating tablet contains 2.10 mg phenylalanine. Information for Patients Migraine or treatment with this product may cause somnolence in some patients. Dizziness has also been reported in some patients receiving this product. Patients should, therefore, evaluate their ability to perform complex tasks during migraine attacks and after administration of this product. Physicians should instruct their patients to read the patient package insert before taking this product. Patients should be cautioned about the risk of serotonin syndrome with the concomitant use of MAXALT and SSRIs or SNRIs. RIZALT-RPD Orally Disintegrating Tablets Patients should be instructed not to remove the blister from the outer pouch until just prior to dosing. The blister pack should then be peeled open with dry hands and the orally disintegrating tablet placed on the tongue, where it will dissolve and be swallowed with the saliva. Laboratory Tests No specific laboratory tests are recommended for monitoring patients prior to and/or after treatment with this product. Drug Interactions Propranolol: Rizatriptan 5 mg should be used in patients taking propranolol, as propranolol has been shown to increase the plasma concentrations of rizatriptan by 70%. Ergot-containing drugs: Ergot-containing drugs have been reported to cause prolonged vasospastic reactions. Because there is a theoretical basis that these effects may be additive, use of ergotamine-containing or ergottype medications (like dihydroergotamine or methysergide) and rizatriptan within 24 hours is contraindicated. Other 5-HT1 agonists: The administration of rizatriptan with other 5-HT1 agonists has not been evaluated in migraine patients. Because their vasospastic effects may be additive, coadministration of rizatriptan and other 5-HT1 agonists within 24 hours of each other is not recommended. Selective serotonin reuptake inhibitors/Serotonin Norepinephrine Reuptake Inhibitors and Serotonin Syndrome: Cases of life-threatening serotonin syndrome have been reported during combined use of SSRIs or SNRIs and triptans. Monoamine oxidase inhibitors: Rizatriptan should not be administered to patients taking MAO-A inhibitors and non-selective MAO inhibitors; it has been shown that moclobemide. Drug/Laboratory Test Interactions this product is not known to interfere with commonly employed clinical laboratory tests. Carcinogenesis, Mutagenesis, Impairment of Fertility Carcinogenesis: The lifetime carcinogenic potential of rizatriptan was evaluated in a 100-week study in mice and a 106-week study in rats at oral gavage doses of up to 125 mg/kg/day. Exposure data were not obtained in those studies, but plasma AUC’s of parent drug measured in other studies after 5 and 21 weeks of oral dosing in mice and rats, respectively, indicate that the exposures to parent drug at the highest dose level in the carcinogenicity studies would have been approximately 150 times (mice) and 240 times (rats) average AUC’s measured in humans after three 10 mg doses, the maximum recommended total daily dose. There was no evidence of an increase in tumor incidence related to rizatriptan in either species.
Mutagenesis: Rizatriptan, with and without metabolic activation, was neither mutagenic, nor clastogenic in a battery of in vitro and in vivo genetic toxicity studies, including: the microbial mutagenesis (Ames) assay, the in vitro mammalian cell mutagenesis assay in V-79 Chinese hamster lung cells, the in vitro alkaline elution assay in rat hepatocytes, the in vitro chromosomal aberration assay in Chinese hamster ovary cells and the in vivo chromosomal aberration assay in mouse bone marrow.
Impairment of Fertility: In a fertility study in rats, altered estrus cyclicity and delays in time to mating were observed in females treated orally with 100 mg/kg/day rizatriptan. Plasma drug exposure (AUC) at this dose was approximately 225 times the exposure in humans receiving the maximum recommended daily dose (MRDD) of 30 mg. The no-effect dose was 10 mg/kg/day (approximately 15 times the human exposure at the MRDD). There were no other fertility-related effects in the female rats. There was no impairment of fertility or reproductive performance in male rats treated with up to 250 mg/kg/day (approximately 550 times the human exposure at the MRDD).
Pregnancy: Pregnancy Category C 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. Maternal drug exposures (AUC) at these doses were approximately 15 and 225 times, respectively, the exposure in humans receiving the maximum recommended daily dose (MRDD) of 30 mg. 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, approximately 7.5 times the exposure 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 of these effects on the offspring in both reproductive toxicity 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 (maternal exposures approximately 225 and 115 times the human exposure at the MRDD in rats and rabbits, respectively). 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. There are no adequate and well-controlled studies in pregnant women; therefore, rizatriptan should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Merck & Co., Inc. maintains a registry to monitor the pregnancy outcomes of women exposed to RIZALT while pregnant.
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 this product is administered to women who are breast-feeding. Rizatriptan is extensively excreted in rat milk, at a level of 5-fold or greater than maternal plasma levels. Pediatric Use Safety and effectiveness of rizatriptan in pediatric patients have not been established; therefore, this product is not recommended for use in patients under 18 years of age. The efficacy of this product Tablets (5 mg) in patients aged 12 to 17 years was not established in a randomized placebo-controlled trial of 291 adolescent migraineurs. Adverse events observed were similar in nature to those reported in clinical trials in adults. Postmarketing experience with other triptans includes a limited number of reports that describe pediatric patients who have experienced clinically serious adverse events that are similar in nature to those reported rarely in adults. The long-term safety of rizatriptan in pediatric patients has not been studied.
Geriatric Use: The pharmacokinetics of rizatriptan were similar in elderly (aged ≥65 years) and in younger adults. Because migraine occurs infrequently in the elderly, clinical experience with this product is limited in such patients. In clinical trials, there were no apparent differences in efficacy or in overall adverse experience rates between patients under 65 years of age and those 65 and above (n=17).
Pediatric Use : Safety and effectiveness of rizatriptan in pediatric patients have not been established; therefore, this product is not recommended for use in patients under 18 years of age. The efficacy of  Tablets (5 mg) in patients aged 12 to 17 years was not established in a randomized placebo-controlled trial of 291 adolescent migraineurs. Adverse events observed were similar in nature to those reported in clinical trials in adults. Postmarketing experience with other triptans includes a limited number of reports that describe pediatric patients who have experienced clinically serious adverse events that are similar in nature to those reported rarely in adults. The long-term safety of rizatriptan in pediatric patients has not been studied.
For full details see prescribing information.

Abdominal pain, palpitations, tachycardia, diarrhea, dyspepsia, thirst, neck pain, stiffness, regional tightness, muscle weakness, decreased mental acuity, insomnia, hypesthesia, tremor, ataxia, nervousness, vertigo, disorientation, dyspnea, pruritus, sweating, blurred vision, hot flashes.
For full details see prescribing information.

For ergotamine/ergot-type medicdbation. The coadministration with other 5-HT1 agonists has not been evaluated in migraine patients. Because their vasospastic effects may be additive, coadministration within 24 hours is not recommended. Selective serotonin reuptake inhibitors (SSRIs), monoamine oxidase inhbitors. In patients receiving propranolol, the 5 mg dose should be used.
For full details see prescribing information.

Pregnancy:  Category C, 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. Maternal drug exposures (AUC) at these doses were approximately 15 and 225 times, respectively, the exposure in humans receiving the maximum recommended daily dose (MRDD) of 30 mg. 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, approximately 7.5 times the exposure 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 of these effects on the offspring in both reproductive toxicity 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 (maternal exposures approximately 225 and 115 times the human exposure at the MRDD in rats and rabbits, respectively). 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. There are no adequate and well-controlled studies in pregnant women; therefore, rizatriptan should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. Merck & Co., Inc. maintains a registry to monitor the pregnancy outcomes of women exposed to this product while pregnant.
Lactation : 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 this product is administered to women who are breast-feeding. Rizatriptan is extensively excreted in rat milk, at a level of 5-fold or greater than maternal plasma levels.

No overdoses of this product were reported during clinical trials. Rizatriptan 40 mg (administered as either a single dose or as two doses with a 2-hour interdose interval) was generally well tolerated in over 300 patients; dizziness and somnolence were the most common drug-related adverse effects. In a clinical pharmacology study in which 12 subjects received rizatriptan, at total cumulative doses of 80 mg (given within four hours), two subjects experienced syncope and/or bradycardia. One subject, a female aged 29 years, developed vomiting, bradycardia, and dizziness beginning three hours after receiving a total of 80 mg rizatriptan (administered over two hours); a third degree AV block, responsive to atropine, was observed an hour after the onset of the other symptoms. The second subject, a 25 year old male, experienced transient dizziness, syncope, incontinence, and a 5-second systolic pause (on ECG monitor) immediately after a painful venipuncture. The venipuncture occurred two hours after the subject had received a total of 80 mg rizatriptan (administered over four hours). In addition, based on the pharmacology of rizatriptan, hypertension or other more serious cardiovascular symptoms could occur after overdose. Gastrointestinal decontamination, (i.e., gastric lavage followed by activated charcoal) should be considered in patients suspected of an overdose with this product. 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.