Maxalt Information
Maxalt () Dosage And Administration
Dosing in pediatric patients is based on the patient's body weight. The recommended dose of Maxalt () 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 Maxalt () within 24 hours in pediatric patients 6 to 17 years of age have not been established.
Maxalt () Dosage Forms And Strengths
Maxalt () Tablets
Maxalt () -MLT Orally Disintegrating Tablets
Maxalt () Contraindications
Maxalt () is contraindicated in patients with:
Maxalt () Warnings And Precautions
Maxalt () 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 Maxalt () . Some of these reactions occurred in patients without known coronary artery disease (CAD). 5-HT agonists including Maxalt () 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 Maxalt () . If there is evidence of CAD or coronary artery vasospasm, Maxalt () should not be administered For patients who have a negative cardiovascular evaluation, consideration should be given to administration of the first Maxalt () dose in a medically-supervised setting and performing an electrocardiogram (ECG) immediately following Maxalt () administration. Periodic cardiovascular evaluation should be considered in intermittent long-term users of Maxalt () who have cardiovascular risk factors.
Cerebral hemorrhage, subarachnoid hemorrhage, and stroke have occurred in patients treated with 5-HT agonists, and some have resulted in fatalities. In a number of cases, it appears possible that the cerebrovascular events were primary, the 5-HT 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 Maxalt () 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. Maxalt () should not be administered to patients with a history of stroke or transient ischemic attack .
5-HT agonists, including Maxalt () , 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 agonist, the suspected vasospasm reaction should be ruled out before receiving additional Maxalt () doses.
Reports of transient and permanent blindness and significant partial vision loss have been reported with the use of 5-HT agonists. Since visual disorders may be part of a migraine attack, a causal relationship between these events and the use of 5-HT agonists have not been clearly established.
Maxalt () Adverse Reactions
The following adverse reactions are discussed in more detail in other sections of the labeling:
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 Maxalt () in their causation cannot be reliably determined.
Neurological/Psychiatric:
Special Senses:
Maxalt () Use In Specific Populations
Safety and effectiveness in pediatric patients under 6 years of age have not been established.
The efficacy and safety of Maxalt () in the acute treatment of migraine in patients aged 6 to 17 years was established in an adequate and well-controlled study .
The incidence of adverse reactions reported for pediatric patients in the acute clinical trial was similar in patients who received Maxalt () to those who received placebo. The adverse reaction pattern in pediatric patients is expected to be similar to that in adults.
Clinical studies of Maxalt () 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 Maxalt () .
Maxalt () Overdosage
No overdoses of Maxalt () were reported during clinical trials in adults.
Some adult patients who received 40 mg of Maxalt () 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 Maxalt () , 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 Maxalt () -MLT 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 Maxalt () , 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 Maxalt () . 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.
Maxalt () Description
Maxalt () contains rizatriptan benzoate, a selective 5-hydroxytryptamine(5-HT) receptor agonist. Rizatriptan benzoate is described chemically as: -dimethyl-5-(1-1,2,4-triazol-1-ylmethyl)-1-indole-3-ethanamine monobenzoate and its structural formula is:
Its empirical formula is CHN•CHO, 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.
Maxalt () Tablets and Maxalt () -MLT Orally Disintegrating 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, pregelatinized starch, ferric oxide (red), and magnesium stearate.
Each lyophilized orally disintegrating tablet contains the following inactive ingredients: gelatin, mannitol, glycine, aspartame, and peppermint flavor.
Maxalt () Clinical Studies
The efficacy of Maxalt () Tablets 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 Maxalt () Tablets 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 Maxalt () 5 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 .
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 .
For patients with migraine-associated photophobia, phonophobia, and nausea at baseline, there was a decreased incidence of these symptoms following administration of Maxalt () 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 .
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.
Maxalt () -MLT Orally Disintegrating Tablets
The efficacy of Maxalt () -MLT was established in two multicenter, randomized, placebo-controlled trials that were similar in design to the trials of Maxalt () Tablets (Studies 5 and 6). Patients were instructed to treat a moderate to severe headache. Patients treated in these studies were primarily female (88%) and Caucasian (95%), with a mean age of 42 years (range 18-72).
In both studies, the percentage of patients achieving headache response 2 hours after treatment was significantly greater in patients who received either Maxalt () -MLT 5 or 10 mg compared to those who received placebo. The results from Studies 5 and 6 are summarized in .
The estimated probability of achieving an initial headache response by 2 hours following treatment with Maxalt () -MLT in pooled Studies 5 and 6 is depicted in .
For patients with migraine-associated photophobia and phonophobia at baseline, there was a decreased incidence of these symptoms following administration of Maxalt () -MLT as 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 .
The efficacy of Maxalt () -MLT 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 non-responders, who then entered into Stage 2, in which patients were randomized to Maxalt () -MLT or placebo. Using a weight-based dosing strategy, patients 20 kg to
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 Maxalt () -MLT, compared with those who received placebo (33% vs. 24%). Study 7 results are summarized in .
The observed percentage of pediatric patients achieving no headache pain within 2 hours following initial treatment with Maxalt () -MLT is shown in .
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 Maxalt () -MLT and those who received placebo.
Maxalt () How Supplied/storage And Handling
No. 3732 — Maxalt () Tablets, 5 mg, are pale pink, capsule-shaped, compressed tablets coded MRK on one side and 266 on the other:
No. 3733 — Maxalt () Tablets, 10 mg, are pale pink, capsule-shaped, compressed tablets coded Maxalt () on one side and MRK 267 on the other:
No. 3800 — Maxalt () -MLT Orally Disintegrating Tablets, 5 mg, are white to off-white, round lyophilized orally disintegrating tablets debossed with a modified triangle on one side, and measuring 10.0-11.5 mm (side-to-side) with a peppermint flavor. Each orally disintegrating tablet is individually packaged in a blister inside an aluminum pouch (sachet). They are supplied as follows:
No. 3801 — Maxalt () -MLT Orally Disintegrating Tablets, 10 mg, are white to off-white, round lyophilized orally disintegrating tablets debossed with a modified square on one side, and measuring 12.0-13.8 mm (side-to-side) with a peppermint flavor. Each orally disintegrating tablet is individually packaged in a blister inside an aluminum pouch (sachet). They are supplied as follows:
Maxalt () Patient Counseling Information
See .
Risk of Myocardial Ischemia and/or Infarction, Prinzmetal's Angina, Other Vasospasm-related Events, and Cerebrovascular Events
Inform patients that Maxalt () 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 .
Serotonin Syndrome
Patients should be cautioned about the risk of serotonin syndrome with the use of Maxalt () or other triptans, particularly during combined use with selective serotonin reuptake inhibitors (SSRIs) or serotonin norepinephrine reuptake inhibitors (SNRIs.
Pregnancy
Inform patients that Maxalt () should not be used during pregnancy unless the potential benefit justifies the potential risk to the fetus .
Nursing Mothers
Advise patients to notify their healthcare provider if they are breastfeeding or plan to breastfeed .
Ability To Perform Complex Tasks
Since migraines or treatment with Maxalt () may cause somnolence and dizziness, instruct patients to evaluate their ability to perform complex tasks during migraine attacks and after administration of Maxalt () .
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) .
Handling of Orally Disintegrating Tablets Packages
Instruct patients not to remove the blister from the outer aluminum pouch until ready to use the orally disintegrating tablet inside .
Patients with Phenylketonuria
Inform phenylketonuric patients that Maxalt () -MLT Orally Disintegrating Tablets contain phenylalanine (a component of aspartame). Each 5-mg orally disintegrating tablet contains 1.1 mg phenylalanine, and each 10-mg orally disintegrating tablet contains 2.1 mg phenylalanine.
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