Maxalt-mlt

— THERAPEUTIC CATEGORIES —
  • Migraine and headache
PAGE CONTENTS
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  • Generic Name & Formulations
  • Indications
  • Dosage and Administration
  • Contraindications
  • Boxed Warnings
  • Warnings/Precautions
  • Pharmacokinetics
  • Interactions
  • Adverse Reactions
  • Clinical Trials
  • Note
  • Patient Counseling

    • Maxalt-mlt Generic Name & Formulations

    Legal Class

    Rx

    General Description

    Rizatriptan (as benzoate) 10mg; orally-disintegrating tabs; peppermint flavor; contains phenylalanine.

    Pharmacological Class

    Selective 5-HT1B/1D receptor agonist.

    See Also

    How Supplied

    Tabs, ODT—18

    How Supplied

    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: 6 x unit of use carrying case of 3 orally disintegrating tablets (18 tablets total). 

    Storage

    Store Maxalt-MLT Orally Disintegrating Tablets at room temperature, 15°C-30°C (59°F-86°F).  

    Manufacturer

    Organon & Co.

    Generic Availability

    YES

    Maxalt-mlt Indications

    Indications

    Acute treatment of migraine with or without aura. 

    Limitations of Use

    Use only where a clear diagnosis of migraine has been established. Not for use in the management of hemiplegic or basilar migraine. Not for prevention of migraine attacks. Safety and effectiveness has not been established for cluster headache.

    Maxalt-mlt Dosage and Administration

    Adult

    ≥18yrs: Initially 5 or 10mg; may repeat after 2hrs; max 30mg/24hrs. Concomitant propranolol: 5mg; max 15mg/24hrs. The safety of treating, on average, more than 4 headaches in a 30-day period has not been established.

    Children

    <6yrs: not established. 6–17yrs (<40kg): 5mg; (≥40kg): 10mg. Concomitant propranolol (≥40kg only): max 5mg/24hrs. The efficacy and safety of treating with ≥1 dose/24hrs have not been established.

    Maxalt-mlt Contraindications

    Contraindications

    Ischemic coronary artery disease (eg, angina pectoris, history of MI, documented silent ischemia). Other significant cardiovascular disease. Coronary artery vasospasm (eg, Prinzmetal's angina). History of stroke or TIA. Peripheral vascular disease. Ischemic bowel disease. Uncontrolled hypertension. Basilar or hemiplegic migraine. Within 24 hours of other 5-HT1 agonists or ergot-type drugs. During or within 2 weeks after discontinuing MAOIs.

    Maxalt-mlt Boxed Warnings

    Not Applicable

    Maxalt-mlt Warnings/Precautions

    Warnings/Precautions

    Confirm diagnosis. Exclude underlying cardiovascular disease; supervise 1st dose and monitor ECG in patients with multiple risk factors (eg, increased age, diabetes, hypertension, smoking, obesity, strong family history of coronary artery disease). Monitor cardiovascular function in long-term intermittent use. Discontinue if life-threatening cardiac rhythm disturbances (including ventricular tachycardia/fibrillation), cerebrovascular events occur. Rule out non-coronary vasospastic reactions if suspected. ODT tabs: Phenylketonuria. Elderly. Pregnancy. Nursing mothers.

    Warnings/Precautions

    Myocardial Ischemia, Myocardial Infarction, and Prinzmetal's Angina 

    • Maxalt is contraindicated in patients with ischemic or vasospastic coronary artery disease. Rare reports of serious cardiac adverse reactions, including acute myocardial infarction, have occurred within a few hours following administration.

    • Prior to receiving Maxalt, perform a cardiovascular evaluation in triptan-naïve patients who have multiple cardiovascular risk factors (e.g., increased age, diabetes, hypertension, smoking, obesity, strong family history of CAD). Do not administer if there is evidence of CAD or coronary artery vasospasm (see Contraindications). For patients with multiple cardiovascular risk factors who have a negative cardiovascular evaluation, consider administering the first Zomig dose in a medically-supervised setting and performing an electrocardiogram (ECG) immediately following administration and consider periodic cardiovascular evaluation in intermittent long-term users of Zomig.

    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 Maxalt if these disturbances occur. 

    Chest, Throat, Neck and/or Jaw Pain/Tightness/Pressure

    • Perform a cardiac evaluation if patients who are at high cardiac risk experience sensations of tightness, pain, and pressure in the chest, throat, neck, and jaw after treatment with Maxalt. 

    • Maxalt is contraindicated in patients with CAD or Prinzmetal’s variant angina.

    Cerebrovascular Events

    • Cerebral hemorrhage, subarachnoid hemorrhage, and stroke have occurred in patients treated with 5-HT1 agonists, and some have resulted in fatalities.

    • May be at increased risk of certain cerebrovascular events (e.g., stroke, hemorrhage, transient ischemic attack). Discontinue Maxalt if a cerebrovascular event occurs. 

    • Exclude other potentially serious neurological conditions before treating headaches in patients not previously diagnosed as migraineurs, and in migraineurs who present with symptoms atypical for migraine. Maxalt is contraindicated in patients with a history of stroke or transient ischemic attack.

    Other Vasospasm Reactions

    • 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.

    • Rule out a vasospastic reaction before receiving additional Relpax doses in patients who experience symptoms or signs suggestive of a non-coronary vasospastic reaction following the use of any 5-HT1 agonist.

    • Reports of transient and permanent blindness and significant partial vision loss have been reported with the use of 5-HT1 agonists. A causal relationship between visual  disorders and the use of 5-HT1 agonists has not been clearly established.  

    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. 

    • May be necessary to detoxify patients, including withdrawal of the overused drugs, and treatment of withdrawal symptoms (which often includes a transient worsening of headache). 

    Serotonin Syndrome

    • The onset of symptoms usually rapidly occurs within minutes to hours of receiving a new or a greater dose of a serotonergic medication. 

    • Discontinue if serotonin syndrome is suspected.

    Increase in Blood Pressure

    • Significant elevations in systemic blood pressure have been reported in patients treated with 5-HT1 agonists including patients without a history of hypertension. 

    • Monitor blood pressure. Maxalt is contraindicated in patients with uncontrolled hypertension.

     

    Pregnancy Considerations

    Risk Summary 

    • Available human data on the use of Maxalt in pregnant women are not sufficient to draw conclusions about drug-associated risk for major birth defects and miscarriage.

    Clinical Considerations 

    • Disease-Associated Maternal and/or Embryo/Fetal Risk: Increased risk of adverse perinatal outcomes in the mother, including pre-eclampsia and gestational hypertension.

    Nursing Mother Considerations

    Risk Summary 

    • There are no data on the presence of rizatriptan or any active metabolites in human milk, or on the effects of rizatriptan on the breastfed infant, or on milk production. 

    • The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for Maxalt or Maxalt -MLT and any potential adverse effects on the breastfed infant from Maxalt or Maxalt-MLT or from the underlying maternal condition. 

    Pediatric Considerations

    Safety and effectiveness in pediatric patients under 6 years of age have not been established. 

    Geriatric Considerations

    Clinical studies of Maxalt did not include sufficient numbers of subjects aged 65 and over to determine whether they respond differently from younger subjects. 

    Use caution for dose selection in an elderly patient, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy.

    Prior to receiving Maxalt, a cardiovascular evaluation is recommended for geriatric patients who have other cardiovascular risk factors (e.g., diabetes, hypertension, smoking, obesity, strong family history of coronary artery disease).

    The pharmacokinetics of Maxalt were similar in geriatric patients (aged > 65 years) compared to younger patients.

    Other Considerations for Specific Populations

    Patients with Phenylketonuria

    • Orally Disintegrating Tablets contain phenylalanine (a component of aspartame). The 5- and 10-mg orally disintegrating tablets contain 1.1 and 2.1 mg phenylalanine, respectively.

    Maxalt-mlt Pharmacokinetics

    Absorption

    Rizatriptan is completely absorbed following oral administration. The mean oral absolute bioavailability of the Maxalt Tablet is about 45%, and mean peak plasma concentrations (Cmax) are reached in approximately 1-1.5 hours (Tmax). The presence of a migraine headache did not appear to affect the absorption or pharmacokinetics of rizatriptan. Food has no significant effect on the bioavailability of rizatriptan but delays the time to reach peak concentration by an hour. In clinical trials, Maxalt was administered without regard to food.

    The bioavailability and Cmax of rizatriptan were similar following administration of Maxalt Tablets and Maxalt-MLT Orally Disintegrating Tablets, but the rate of absorption is somewhat slower with Maxalt-MLT, with Tmax delayed by up to 0.7 hour. AUC of rizatriptan is approximately 30% higher in females than in males. No accumulation occurred on multiple dosing.  

    Distribution

    The mean volume of distribution is approximately 140 liters in male subjects and 110 liters in female subjects. Rizatriptan is minimally bound (14%) to plasma proteins.

    Metabolism

    The primary route of rizatriptan metabolism is via oxidative deamination by monoamine oxidase-A (MAO-A) to the indole acetic acid metabolite, which is not active at the 5-HT1B/1D receptor. N-monodesmethyl-rizatriptan, a metabolite with activity similar to that of parent compound at the 5-HT1B/1D receptor, is formed to a minor degree. Plasma concentrations of N-monodesmethyl-rizatriptan are approximately 14% of those of parent compound, and it is eliminated at a similar rate. Other minor metabolites, the N-oxide, the 6-hydroxy compound, and the sulfate conjugate of the 6-hydroxy metabolite are not active at the 5-HT1B/1D receptor. 

    Elimination

    The total radioactivity of the administered dose recovered over 120 hours in urine and feces was 82% and 12%, respectively, following a single 10-mg oral administration of 14C-rizatriptan. Following oral administration of 14C-rizatriptan, rizatriptan accounted for about 17% of circulating plasma radioactivity. Approximately 14% of an oral dose is excreted in urine as unchanged rizatriptan while 51% is excreted as indole acetic acid metabolite, indicating substantial first pass metabolism. The plasma half-life of rizatriptan in males and females averages 2-3 hours.

    Special Populations

    • Gender: The mean AUC0-∞ and Cmax of rizatriptan (10 mg orally) were about 30% and 11% higher in females as compared to males, respectively, while Tmax occurred at approximately the same time.

    • Hepatic impairment: Following oral administration in patients with hepatic impairment caused by mild to moderate alcoholic cirrhosis of the liver, plasma concentrations of rizatriptan were similar in patients with mild hepatic insufficiency compared to a control group of subjects with normal hepatic function; plasma concentrations of rizatriptan were approximately 30% greater in patients with moderate hepatic insufficiency. 

    • Renal impairment: In patients with renal impairment (creatinine clearance 10-60 mL/min/1.73 m2), the AUC0-∞ of rizatriptan was not significantly different from that in subjects with normal renal function. In hemodialysis patients, (creatinine clearance <2 mL/min/1.73 m2), however, the AUC for rizatriptan was approximately 44% greater than that in patients with normal renal function.

    Maxalt-mlt Interactions

    Interactions

    See Contraindications. Potentiated by propranolol (see Adults, Children). Serotonin syndrome with concomitant SSRIs, SNRIs, TCAs, MAOIs; discontinue if suspected.

    Maxalt-mlt Adverse Reactions

    Adverse Reactions

    Asthenia, fatigue, somnolence, chest/throat/neck/jaw pressure/pain, dizziness; arrhythmias, cerebrovascular events, other vasospasms, hypertension, medication overuse headache.

    Maxalt-mlt Clinical Trials

    Clinical Trials

    Adults: 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) for the treatment of 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, results showed that a significantly greater percentage of patients treated with Maxalt-MLT 5 or 10 mg achieved headache response 2 hours after treatment compared with those who received placebo. The following percentages of patients achieved headache response 2 hours after treatment of initial headache in Studies 5 and 6:

    • Study 5:

      • Maxalt-MLT 5 mg: 66% (n=100; P <.01 in comparison with placebo); Maxalt-MLT 10 mg: 66% (n=113; P <.01 in comparison with placebo) vs placebo: 47% (n=98)

    • Study 6:

      • Maxalt-MLT 5 mg: 59% (n=181; P <.01 in comparison with placebo); Maxalt-MLT 10 mg: 74% (n=186; P <.01 in comparison with 5 mg) vs placebo: 28% (n=180)

    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.  

     

    Pediatric Patients 6 to 17 Years of Age

    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), and were 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. Patients who weighed between 20 kg to <40 kg (44 lb to <88 lb) received Maxalt-MLT 5 mg or placebo, and patients who weighed ≥40 kg (88 lb) received Maxalt-MLT 10 mg or placebo.

    Results showed that a significantly greater percentage of patients who received Maxalt-MLT achieved no headache pain at 2 hours after treatment (primary efficacy endpoint) compared with those who received placebo (33% [n=126/382] vs. 24% [n=94/388]; P =.01). 

    There was no statistically significant difference between patients who received Maxalt-MLT and those who received placebo regarding the absence of migraine-associated symptoms (nausea, photophobia, and phonophobia) at 2 hours after taking the dose. 

    Maxalt-mlt Note

    Not Applicable

    Maxalt-mlt Patient Counseling

    Patient Counseling

    Risk of Myocardial Ischemia and/or Infarction, Prinzmetal's Angina, Other Vasospasm-Related Events, and Cerebrovascular Events

    • May cause serious cardiovascular side effects such as myocardial infarction or stroke, which 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. 

    Serotonin Syndrome

    • Risk of serotonin syndrome with the use of Maxalt or other triptans, especially concomitant use with selective serotonin reuptake inhibitors (SSRIs) or serotonin norepinephrine reuptake inhibitors (SNRIs).

    Pregnancy

    • Do not use during pregnancy unless the potential benefit justifies the potential risk to the fetus. 

    Lactation

    • Advise patients to notify their healthcare provider if they are breastfeeding or plan to breastfeed.

    Ability to Perform Complex Tasks 

    • 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

    • Do not 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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