Remeron Soltab Information
Remeron soltab (Mirtazapine)
Remeron soltab (Mirtazapine) Description
REMERONSolTab (mirtazapine) Orally Disintegrating Tablets are an orally administered drug. Mirtazapine has a tetracyclic chemical structure and belongs to the piperazino-azepine group of compounds. It is designated 1,2,3,4,10,14b-hexahydro-2-methylpyrazino [2,1-a] pyrido [2,3-c] benzazepine and has the empirical formula of CHN. Its molecular weight is 265.36. The structural formula is the following and it is the racemic mixture:
Mirtazapine is a white to creamy white crystalline powder which is slightly soluble in water. REMERONSolTab is available for oral administration as an orally disintegrating tablet containing 15, 30, or 45 mg of mirtazapine. It disintegrates in the mouth within seconds after placement on the tongue, allowing its contents to be subsequently swallowed with or without water. REMERONSolTab also contains the following inactive ingredients: aspartame, citric acid, crospovidone, hypromellose, magnesium stearate, mannitol, microcrystalline cellulose, natural and artificial orange flavor, polymethacrylate, povidone, sodium bicarbonate, starch, and sucrose.
Remeron soltab (Mirtazapine) Clinical Pharmacology
The mechanism of action of REMERONSolTab (mirtazapine) Orally Disintegrating Tablets, as with other drugs effective in the treatment of major depressive disorder, is unknown.
Evidence gathered in preclinical studies suggests that mirtazapine enhances central noradrenergic and serotonergic activity. These studies have shown that mirtazapine acts as an antagonist at central presynaptic α adrenergic inhibitory autoreceptors and heteroreceptors, an action that is postulated to result in an increase in central noradrenergic and serotonergic activity.
Mirtazapine is a potent antagonist of 5-HT and 5-HT receptors. Mirtazapine has no significant affinity for the 5-HT and 5-HT receptors.
Mirtazapine is a potent antagonist of histamine (H) receptors, a property that may explain its prominent sedative effects.
Mirtazapine is a moderate peripheral α adrenergic antagonist, a property that may explain the occasional orthostatic hypotension reported in association with its use.
Mirtazapine is a moderate antagonist at muscarinic receptors, a property that may explain the relatively low incidence of anticholinergic side effects associated with its use.
REMERONSolTab (mirtazapine) Orally Disintegrating Tablets are rapidly and completely absorbed following oral administration and have a half-life of about 20 to 40 hours. Peak plasma concentrations are reached within about 2 hours following an oral dose. The presence of food in the stomach has a minimal effect on both the rate and extent of absorption and does not require a dosage adjustment. REMERONSolTab Orally Disintegrating Tablets are bioequivalent to REMERON (mirtazapine) Tablets.
Mirtazapine is extensively metabolized after oral administration. Major pathways of bio-transformation are demethylation and hydroxylation followed by glucuronide conjugation. data from human liver microsomes indicate that cytochrome 2D6 and 1A2 are involved in the formation of the 8-hydroxy metabolite of mirtazapine, whereas cytochrome 3A is considered to be responsible for the formation of the N-desmethyl and N-oxide metabolite. Mirtazapine has an absolute bioavailability of about 50%. It is eliminated predominantly via urine (75%) with 15% in feces. Several unconjugated metabolites possess pharmacological activity but are present in the plasma at very low levels. The (–) enantiomer has an elimination half-life that is approximately twice as long as the (+) enantiomer and therefore achieves plasma levels that are about 3 times as high as that of the (+) enantiomer.
Plasma levels are linearly related to dose over a dose range of 15 to 80 mg. The mean elimination half-life of mirtazapine after oral administration ranges from approximately 20 to 40 hours across age and gender subgroups, with females of all ages exhibiting significantly longer elimination half-lives than males (mean half-life of 37 hours for females vs. 26 hours for males). Steady state plasma levels of mirtazapine are attained within 5 days, with about 50% accumulation (accumulation ratio = 1.5).
Mirtazapine is approximately 85% bound to plasma proteins over a concentration range of 0.01 to 10 mcg/mL.
Remeron soltab (Mirtazapine) Indications And Usage
REMERONSolTab (mirtazapine) Orally Disintegrating Tablets are indicated for the treatment of major depressive disorder.
The efficacy of REMERON (mirtazapine) Tablets in the treatment of major depressive disorder was established in 6-week controlled trials of outpatients whose diagnoses corresponded most closely to the Diagnostic and Statistical Manual of Mental Disorders – 3rd edition (DSM-III) category of major depressive disorder (see ).
A major depressive episode (DSM-IV) implies a prominent and relatively persistent (nearly every day for at least 2 weeks) depressed or dysphoric mood that usually interferes with daily functioning, and includes at least 5 of the following 9 symptoms: depressed mood, loss of interest in usual activities, significant change in weight and/or appetite, insomnia or hypersomnia, psychomotor agitation or retardation, increased fatigue, feelings of guilt or worthlessness, slowed thinking or impaired concentration, a suicide attempt, or suicidal ideation.
The effectiveness of REMERONSolTab in hospitalized depressed patients has not been adequately studied.
The efficacy of REMERON in maintaining a response in patients with major depressive disorder for up to 40 weeks following 8 to 12 weeks of initial open-label treatment was demonstrated in a placebo-controlled trial. Nevertheless, the physician who elects to use REMERON for extended periods should periodically re-evaluate the long-term usefulness of the drug for the individual patient (see ).
Remeron soltab (Mirtazapine) Warnings
Patients with major depressive disorder (MDD), both adult and pediatric, may experience worsening of their depression and/or the emergence of suicidal ideation and behavior (suicidality) or unusual changes in behavior, whether or not they are taking antidepressant medications, and this risk may persist until significant remission occurs. Suicide is a known risk of depression and certain other psychiatric disorders, and these disorders themselves are the strongest predictors of suicide. There has been a long-standing concern, however, that antidepressants may have a role in inducing worsening of depression and the emergence of suicidality in certain patients during the early phases of treatment. Pooled analyses of short-term placebo-controlled trials of antidepressant drugs (SSRIs and others) showed that these drugs increase the risk of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults (ages 18–24) with major depressive disorder (MDD) and other psychiatric disorders. Short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond age 24; there was a reduction in risk with antidepressants compared to placebo in adults aged 65 and older.
The pooled analyses of placebo-controlled trials in children and adolescents with MDD, obsessive compulsive disorder (OCD), or other psychiatric disorders included a total of 24 short-term trials of 9 antidepressant drugs in over 4400 patients. The pooled analyses of placebo-controlled trials in adults with MDD or other psychiatric disorders included a total of 295 short-term trials (median duration of 2 months) of 11 antidepressant drugs in over 77,000 patients. There was considerable variation in risk of suicidality among drugs, but a tendency toward an increase in the younger patients for almost all drugs studied. There were differences in absolute risk of suicidality across different indications, with the highest incidence in MDD. The risk differences (drug vs. placebo), however, were relatively stable within age strata and across indications. These risk differences (drug-placebo difference in the number of cases of suicidality per 1000 patients treated) are provided in .
No suicides occurred in any of the pediatric trials. There were suicides in the adult trials, but the number was not sufficient to reach any conclusion about drug effect on suicide.
It is unknown whether the suicidality risk extends to longer-term use, i.e., beyond several months. However, there is substantial evidence from placebo-controlled maintenance trials in adults with depression that the use of antidepressants can delay the recurrence of depression.
All patients being treated with antidepressants for any indication should be monitored appropriately and observed closely for clinical worsening, suicidality, and unusual changes in behavior, especially during the initial few months of a course of drug therapy, or at times of dose changes, either increases or decreases.
The following symptoms, anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia (psychomotor restlessness), hypomania, and mania, have been reported in adult and pediatric patients being treated with antidepressants for major depressive disorder as well as for other indications, both psychiatric and nonpsychiatric. Although a causal link between the emergence of such symptoms and either the worsening of depression and/or the emergence of suicidal impulses has not been established, there is concern that such symptoms may represent precursors to emerging suicidality.
Consideration should be given to changing the therapeutic regimen, including possibly discontinuing the medication, in patients whose depression is persistently worse, or who are experiencing emergent suicidality or symptoms that might be precursors to worsening depression or suicidality, especially if these symptoms are severe, abrupt in onset, or were not part of the patient's presenting symptoms.
Families and caregivers of patients being treated with antidepressants for major depressive disorder or other indications, both psychiatric and nonpsychiatric, should be alerted about the need to monitor patients for the emergence of agitation, irritability, unusual changes in behavior, and the other symptoms described above, as well as the emergence of suicidality, and to report such symptoms immediately to health care providers. Such monitoring should include daily observation by families and caregivers.
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In premarketing clinical trials, 2 (1 with Sjögren's Syndrome) out of 2796 patients treated with REMERON (mirtazapine) Tablets developed agranulocytosis [absolute neutrophil count (ANC)
In patients receiving other drugs for major depressive disorder in combination with a monoamine oxidase inhibitor (MAOI) and in patients who have recently discontinued a drug for major depressive disorder and then are started on an MAOI, there have been reports of serious and sometimes fatal reactions, including nausea, vomiting, flushing, dizziness, tremor, myoclonus, rigidity, diaphoresis, hyperthermia, autonomic instability with rapid fluctuations of vital signs, seizures, and mental status changes ranging from agitation to coma. Although there are no human data pertinent to such an interaction with REMERONSolTab (mirtazapine) Orally Disintegrating Tablets, it is recommended that REMERONSolTab not be used in combination with an MAOI, or within 14 days of initiating or discontinuing therapy with an MAOI.
The development of a potentially life-threatening serotonin syndrome or Neuroleptic Malignant Syndrome (NMS)-like reactions have been reported with SSRIs, SNRIs, MAOIs, and other serotonergic drugs used as monotherapy, including REMERONSolTab, but particularly with concomitant use of serotonergic drugs (including triptans) with drugs which impair metabolism of serotonin (including MAOIs), or with antipsychotics or other dopamine antagonists. 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). Serotonin syndrome, in its most severe form can resemble neuroleptic malignant syndrome, which includes hyperthermia, muscle rigidity, autonomic instability with possible rapid fluctuation of vital signs, and mental status changes. Patients should be monitored for the emergence of serotonin syndrome or NMS-like signs and symptoms.
The concomitant use of REMERONSolTab with MAOIs intended to treat depression is contraindicated [ ].
If concomitant treatment of REMERONSolTab with a 5-hydroxytryptamine receptor agonist (triptan) is clinically warranted, careful observation of the patient is advised, particularly during treatment initiation and dose increases.
The concomitant use of REMERONSolTab with serotonin precursors (such as tryptophan) is not recommended.
Treatment with REMERONSolTab and any concomitant serotonergic or antidopaminergic agents, including antipsychotics, should be discontinued immediately if the above events occur and supportive symptomatic treatment should be initiated.
Remeron soltab (Mirtazapine) Precautions
Prescribers or other health professionals should inform patients, their families, and their caregivers about the benefits and risks associated with treatment with REMERONSolTab (mirtazapine) Orally Disintegrating Tablets and should counsel them in its appropriate use. A patient Medication Guide about "Antidepressant Medicines, Depression and other Serious Mental Illnesses, and Suicidal Thoughts or Actions" is available for REMERONSolTab. The prescriber or health professional should instruct patients, their families, and their caregivers to read the Medication Guide and should assist them in understanding its contents. Patients should be given the opportunity to discuss the contents of the Medication Guide and to obtain answers to any questions they may have. The complete text of the Medication Guide is reprinted at the end of this document.
Patients should be advised of the following issues and asked to alert their prescriber if these occur while taking REMERONSolTab.
Safety and effectiveness in the pediatric population have not been established (see and ). Two placebo-controlled trials in 258 pediatric patients with MDD have been conducted with REMERON (mirtazapine) Tablets, and the data were not sufficient to support a claim for use in pediatric patients. Anyone considering the use of REMERONSolTab (mirtazapine) Orally Disintegrating Tablets in a child or adolescent must balance the potential risks with the clinical need.
In an 8-week-long pediatric clinical trial of doses between 15 to 45 mg/day, 49% of REMERON-treated patients had a weight gain of at least 7%, compared to 5.7% of placebo-treated patients. The mean increase in weight was 4 kg (2 kg SD) for REMERON-treated patients versus 1 kg (2 kg SD) for placebo-treated patients (see ).
Remeron soltab (Mirtazapine) Adverse Reactions
Table 4
The prescriber should be aware that these figures cannot be used to predict the incidence of side effects in the course of usual medical practice where patient characteristics and other factors differ from those which prevailed in the clinical trials. Similarly, the cited frequencies cannot be compared with figures obtained from other investigations involving different treatments, uses, and investigators. The cited figures, however, do provide the prescribing physician with some basis for estimating the relative contribution of drug and nondrug factors to the side-effect incidence rate in the population studied.
During its premarketing assessment, multiple doses of REMERON (mirtazapine) Tablets were administered to 2796 patients in clinical studies. The conditions and duration of exposure to mirtazapine varied greatly, and included (in overlapping categories) open and double-blind studies, uncontrolled and controlled studies, inpatient and outpatient studies, fixed-dose and titration studies. Untoward events associated with this exposure were recorded by clinical investigators using terminology of their own choosing. Consequently, it is not possible to provide a meaningful estimate of the proportion of individuals experiencing adverse events without first grouping similar types of untoward events into a smaller number of standardized event categories.
In the tabulations that follow, reported adverse events were classified using a standard COSTART-based dictionary terminology. The frequencies presented, therefore, represent the proportion of the 2796 patients exposed to multiple doses of REMERON who experienced an event of the type cited on at least 1 occasion while receiving REMERON. All reported events are included except those already listed in , those adverse experiences subsumed under COSTART terms that are either overly general or excessively specific so as to be uninformative, and those events for which a drug cause was very remote. It is important to emphasize that, although the events reported occurred during treatment with REMERON, they were not necessarily caused by it.
Events are further categorized by body system and listed in order of decreasing frequency according to the following definitions: frequent adverse events are those occurring on 1 or more occasions in at least 1/100 patients; infrequent adverse events are those occurring in 1/100 to 1/1000 patients; rare events are those occurring in fewer than 1/1000 patients. Only those events not already listed in appear in this listing. Events of major clinical importance are also described in the WARNINGS and PRECAUTIONS sections.
Adverse events reported since market introduction, which were temporally (but not necessarily causally) related to mirtazapine therapy, include 4 cases of the ventricular arrhythmia torsades de pointes. In 3 of the 4 cases, however, concomitant drugs were implicated. All patients recovered.
Cases of severe skin reactions, including Stevens-Johnson Syndrome, bullous dermatitis, erythema multiforme and toxic epidermal necrolysis have also been reported.
Remeron soltab (Mirtazapine) Overdosage
Treatment should consist of those general measures employed in the management of overdose with any drug effective in the treatment of major depressive disorder. Ensure an adequate airway, oxygenation, and ventilation. Monitor cardiac rhythm and vital signs. General supportive and symptomatic measures are also recommended. Induction of emesis is not recommended. Gastric lavage with a large-bore orogastric tube with appropriate airway protection, if needed, may be indicated if performed soon after ingestion, or in symptomatic patients. Because of the rapid disintegration of REMERONSolTab (mirtazapine) Orally Disintegrating Tablets, pill fragments may not appear in gastric contents obtained with lavage. Activated charcoal should be administered. There is no experience with the use of forced diuresis, dialysis, hemoperfusion, or exchange transfusion in the treatment of mirtazapine overdosage. No specific antidotes for mirtazapine are known.
In managing overdosage, consider the possibility of multiple-drug involvement. The physician should consider contacting a poison control center for additional information on the treatment of any overdose. Telephone numbers for certified poison control centers are listed in the (PDR).
Remeron soltab (Mirtazapine) How Supplied
REMERONSolTab (mirtazapine) Orally Disintegrating Tablets are supplied as:
Remeron soltab (Mirtazapine)
Remeron soltab (Mirtazapine) Medication Guide
REMERONSolTab (rĕm' - ĕ - rŏn - sŏl' – tăb)(mirtazapine)Orally Disintegrating Tablets
Read the Medication Guide that comes with REMERONSolTab before you start taking it and each time you get a refill. There may be new information. This Medication Guide does not take the place of talking to your healthcare provider about your medical condition or treatment. If you have any questions about REMERONSolTab, talk to your healthcare provider.
REMERONSolTab and other antidepressant medicines may cause serious side effects, including:
REMERONSolTab is a prescription medicine used to treat depression. It is important to talk with your healthcare provider about the risks of treating depression and also the risks of not treating it. You should discuss all treatment choices with your healthcare provider.
Talk to your healthcare provider if you do not think that your condition is getting better with REMERONSolTab treatment.
Do not take REMERONSolTab if you:
Before starting REMERONSolTab, tell your healthcare provider if you:
Your healthcare provider or pharmacist can tell you if it is safe to take REMERONSolTab with your other medicines. Do not start or stop any medicine while taking REMERONSolTab without talking to your healthcare provider first.
REMERONSolTab may cause serious side effects, including all of those described in the section entitled ""
Common possible side effects in people who take REMERONSolTab include:
Tell your healthcare provider if you have any side effect that bothers you or that does not go away. These are not all the possible side effects of REMERONSolTab. For more information, ask your healthcare provider or pharmacist.
Medicines are sometimes prescribed for purposes other than those listed in a Medication Guide. Do not use REMERONSolTab for a condition for which it was not prescribed. Do not give REMERONSolTab to other people, even if they have the same condition. It may harm them.
This Medication Guide summarizes the most important information about REMERONSolTab. If you would like more information, talk with your healthcare provider. You may ask your healthcare provider or pharmacist for information about REMERONSolTab that is written for healthcare professionals.
For more information about REMERONSolTab call 1-800-526-4099 or go to www.REMERONSolTab.com.
Active ingredient: mirtazapine
Inactive ingredients 15mg, 30mg and 45mg tablets: Aspartame, citric acid anhydrous, crospovidone, magnesium stearate, mannitol, microcrystalline cellulose, natural and artificial orange flavor, sodium bicarbonate, hypromellose, povidone, sugar spheres, Eudragit E100.
This Medication Guide has been approved by the U.S. Food and Drug Administration.
Remeron soltab (Mirtazapine) Principal Display Panel - Mg Carton
NDC 0052--30
30 Tablets
ONCE-A-DAY (mirtazapine) Orally Disintegrating Tablets
Rx only
Manufactured by: CIMA LABS INC., Eden Prairie, MN 55344, USA Distributed by: Schering Corporation, a subsidiary of Whitehouse Station, NJ 08889, USA
CIMA is a registered trademark of CIMA LABS INC.
Remeron soltab (Mirtazapine) Principal Display Panel - Mg Carton
NDC 0052--30
30 Tablets
ONCE-A-DAY (mirtazapine) Orally Disintegrating Tablets
Rx only
Manufactured by: CIMA LABS INC., Eden Prairie, MN 55344, USA Distributed by: Schering Corporation, a subsidiary of Whitehouse Station, NJ 08889, USA
CIMA is a registered trademark of CIMA LABS INC.
Remeron soltab (Mirtazapine) Principal Display Panel - Mg Carton
NDC 0052--30
30 Tablets
ONCE-A-DAY (mirtazapine) Orally Disintegrating Tablets
Rx only
Manufactured by: CIMA LABS INC., Eden Prairie, MN 55344, USA Distributed by: Schering Corporation, a subsidiary of Whitehouse Station, NJ 08889, USA
CIMA is a registered trademark of CIMA LABS INC.
