Mirtazon - General Information
Mirtazon is an antidepressant introduced by Organon International in 1996 used for the treatment of moderate to severe depression. Mirtazon has a tetracyclic chemical structure and is classified as a noradrenergic and specific serotonergic antidepressant (NaSSA). It is the only tetracyclic antidepressant that has been approved by the Food and Drug Administration to treat depression. [Wikipedia]
Pharmacology of Mirtazon
Mirtazon, an antidepressant of the piperazinoazepine class, is a tetracyclic compound with an anxiolytic effect. Mirtazon has fewer ADRs than tricyclic antidepressants and is better tolerated. Selective blockade of specific serotonin receptors by mirtazapine likey minimizes side effects typical of other antidepressants.
Mirtazon for patients
Prescribers or other health professionals should inform patients, their families, and their caregivers about the benefits and risks associated with treatment with REMERONSolTabÒ (mirtazapine) Orally Disintegrating Tablets and should counsel them in its appropriate use. A patient Medication Guide About Using Antidepressants in Children and Teenagers is available for REMERONSolTabÒ . 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 REMERONSolTabÒ.
Clinical Worsening and Suicide Risk
Patients, their families, and their caregivers should be encouraged to be alert to the emergence of anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia (psychomotor restlessness), hypomania, mania, other unusual changes in behavior, worsening of depression, and suicidal ideation, especially early during antidepressant treatment and when the dose is adjusted up or down. Families and caregivers of patients should be advised to observe for the emergence of such symptoms on a day-to-day basis, since changes may be abrupt. Such symptoms should be reported to the patientís prescriber or health professional, especially if they are severe, abrupt in onset, or were not part of the patientís presenting symptoms. Symptoms such as these may be associated with an increased risk for suicidal thinking and behavior and indicate a need for very close monitoring and possibly changes in the medication.
Patients who are to receive REMERONSolTabÒ should be warned about the risk of developing agranulocytosis. Patients should be advised to contact their physician if they experience any indication of infection such as fever, chills, sore throat, mucous membrane ulceration or other possible signs of infection. Particular attention should be paid to any flu-like complaints or other symptoms that might suggest infection.
Interference with Cognitive and Motor Performance
REMERONSolTabÒ may impair judgement, thinking, and particularly, motor skills, because of its prominent sedative effect. The drowsiness associated with mirtazapine use may impair a patientís ability to drive, use machines or perform tasks that require alertness. Thus, patients should be cautioned about engaging in hazardous activities until they are reasonably certain that REMERONSolTabÒ therapy does not adversely affect their ability to engage in such activities.
Completing Course of Therapy
While patients may notice improvement with REMERONSolTabÒ therapy in 1- 4 weeks, they should be advised to continue therapy as directed.
Patients should be advised to inform their physician if they are taking, or intend to take, any prescription or over-the-counter drugs since there is a potential for REMERONSolTabÒ to interact with other drugs.
The impairment of cognitive and motor skills produced by REMERONÒ has been shown to be additive with those produced by alcohol. Accordingly, patients should be advised to avoid alcohol while taking any dosage form of mirtazapine.
Phenylketonuric patients should be informed that REMERONSolTabÒ contains phenylalanine 2.6 mg per 15 mg tablet, 5.2 mg per 30 mg tablet, and 7.8 mg per 45 mg tablet.
Patients should be advised to notify their physician if they become pregnant or
intend to become pregnant during REMERONSolTabÒ therapy.
Patients should be advised to notify their physician if they are breast-feeding an infant.
There are no routine laboratory tests recommended.
About Using Antidepressants in Children and Teenagers What is the most important information I should know if my child is being prescribed an antidepressant?
Parents or guardians need to think about 4 important things when their child is prescribed an antidepressant:
1. There is a risk of suicidal thoughts or actions
2. How to try to prevent suicidal thoughts or actions in your child
3. You should watch for certain signs if your child is taking an antidepressant
4. There are benefits and risks when using antidepressants
1. There is a Risk of Suicidal Thoughts or Actions
Children and teenagers sometimes think about suicide, and many report trying to kill themselves.
Antidepressants increase suicidal thoughts and actions in some children and teenagers. But suicidal thoughts and actions can also be caused by depression, a serious medical condition that is commonly treated with antidepressants. Thinking about killing yourself or trying to kill yourself is called suicidality or being suicidal.
A large study combined the results of 24 different studies of children and teenagers with depression or other illnesses. In these studies, patients took either a placebo (sugar pill) or an antidepressant for 1 to 4 months. No one committed suicide in these studies, but some patients became suicidal. On sugar pills, 2 out of every 100 became suicidal. On the antidepressants, 4 out of every 100 patients became suicidal.
For some children and teenagers, the risks of suicidal actions may be especially high. These include patients with:
· Bipolar illness (sometimes called manic-depressive illness)
· A family history of bipolar illness
· A personal or family history of attempting suicide If any of these are present, make sure you tell your healthcare provider before your child takes an antidepressant.
2. How to Try to Prevent Suicidal Thoughts and Actions
To try to prevent suicidal thoughts and actions in your child, pay close attention to changes in her or his moods or actions, especially if the changes occur suddenly. Other important people in your childís life can help by paying attention as well (e.g., your child, brothers and sisters, teachers, and other important people). The changes to look out for are listed in Section 3, on what to watch for.
Whenever an antidepressant is started or its dose is changed, pay close attention to your child.
After starting an antidepressant, your child should generally see his or her healthcare provider:
· Once a week for the first 4 weeks
· Every 2 weeks for the next 4 weeks
· After taking the antidepressant for 12 weeks
· After 12 weeks, follow your healthcare providerís advice about how often to come back
· More often if problems or questions arise
You should call your childís healthcare provider between visits if needed.
3. You Should Watch for Certain Signs If Your Child is Taking an Antidepressant
Contact your childís healthcare provider right away if your child exhibits any of the following signs for the first time, or if they seem worse, or worry you, your child, or your childís teacher:
· Thoughts about suicide or dying
· Attempts to commit suicide
· New or worse depression
· New or worse anxiety
· Feeling very agitated or restless
· Difficulty sleeping (insomnia)
· New or worse irritability
· Acting aggressive, being angry, or violent
· Acting on dangerous impulses
· An extreme increase in activity and talking
· Other unusual changes in behavior or mood
Never let your child stop taking an antidepressant without first talking to his or her healthcare provider. Stopping an antidepressant suddenly can cause other symptoms.
4. There are Benefits and Risks When Using Antidepressants
Antidepressants are used to treat depression and other illnesses. Depression and other illnesses can lead to suicide. In some children and teenagers, treatment with an antidepressant increases suicidal thinking or actions. It is important to discuss all the risks of treating depression and also the risks of not treating it. You and your child should discuss all treatment choices with your healthcare provider, not just the use of antidepressants.
Other side effects can occur with antidepressants.
Of all the antidepressants, only fluoxetine (Prozac ) has been FDA approved to treat pediatric depression.
For obsessive compulsive disorder in children and teenagers, FDA has approved only fluoxetine (Prozac ), sertraline (Zoloft ), fluvoxamine, and clomipramine (Anafranil ).
Your healthcare provider may suggest other antidepressants based on the past experience of your child or other family members.
Is this all I need to know if my child is being prescribed an antidepressant?
No. This is a warning about the risk for suicidality. Other side effects can occur with antidepressants. Be sure to ask your healthcare provider to explain all the side
effects of the particular drug he or she is prescribing. Also ask about drugs to avoid when taking an antidepressant. Ask your healthcare provider or pharmacist where to find more information.
*ProzacÒ is a registered trademark of Eli Lilly and Company
*ZoloftÒ is a registered trademark of Pfizer Pharmaceuticals
*AnafranilÒ is a registered trademark of Mallinckrodt Inc.
This Medication Guide has been approved by the U.S. Food and Drug Administration for all antidepressants.
As with other drugs, the potential for interaction by a variety of mechanisms (e.g., pharmacodynamic, pharmacokinetic inhibition or enhancement, etc.) is a possibility.
Drugs Affecting Hepatic Metabolism
The metabolism and pharmacokinetics of REMERONSolTabÒ (mirtazapine) Orally Disintegrating Tablets may be affected by the induction or inhibition of drug-metab-olizing enzymes.
Drugs that are Metabolized by and/or Inhibit Cytochrome P450 Enzymes
Many drugs are metabolized by and/or inhibit various cytochrome P450 enzymes, e.g., 2D6, 1A2, 3A4, etc. In vitro studies have shown that mirtazapine is a substrate for several of these enzymes, including 2D6, 1A2, and 3A4. While in vitro studies have shown that mirtazapine is not a potent inhibitor of any of these enzymes, an indication that mirtazapine is not likely to have a clinically significant inhibitory effect on the metabolism of other drugs that are substrates for these cytochrome P450 enzymes, the concomitant use of REMERONSolTabÒ with most other drugs metabolized by these enzymes has not been formally studied. Consequently, it is not possible to make any definitive statements about the risks of coadministration of REMERONSolTab with such drugs.
Concomitant administration of alcohol (equivalent to 60 g) had a minimal effect on plasma levels of mirtazapine (15 mg) in 6 healthy male subjects. However, the impairment of cognitive and motor skills produced by REMERONÒ were shown to be additive with those produced by alcohol. Accordingly, patients should be advised to avoid alcohol while taking REMERONSolTabÒ.
Concomitant administration of diazepam (15 mg) had a minimal effect on plasma levels of mirtazapine (15 mg) in 12 healthy subjects. However, the impairment of motor skills produced by REMERONÒ has been shown to be additive with those caused by diazepam. Accordingly, patients should be advised to avoid diazepam and other similar drugs while taking REMERONSolTabÒ.
REMERONSolTabÒ (mirtazapine) Orally Disintegrating Tablets are contraindicated in patients with a known hypersensitivity to mirtazapine.
Additional information about Mirtazon
Mirtazon Indication: For the treatment of major depressive disorder.
Mechanism Of Action: Mirtazon acts as an antagonist at central pre-synaptic alpha(2)-receptors, inhibiting negative feedback to the presynaptic nerve and causing an increase in NE release. Blockade of heteroreceptors, alpha(2)-receptors contained in serotenergic neurons, enhances the release of 5-HT, increasing the interactions between 5-HT and 5-HT1 receptors and contributing to the anxiolytic effects of mirtazapine. Mirtazon also acts as a weak antagonist at 5-HT1 receptors and as a potent antagonist at 5-HT2 (particularly subtypes 2A and 2C) and 5-HT3 receptors. Blockade of these receptors may explain the lower incidence of adverse effects such as anxiety, insomnia, and nausea. Mirtazon also exhibits significant antagonism at H1-receptors, resulting in sedation. Mirtazon has no effects on the reuptake of either NE or 5-HT and has only minimal activity at dopaminergic and muscarinic receptors.
Drug Interactions: Clonidine Possible hypertensive crisis
Tranylcypromine Possible severe adverse reaction with this combination
Rasagiline Possible severe adverse reaction with this combination
Phenelzine Possible severe adverse reaction with this combination
Isocarboxazid Possible severe adverse reaction with this combination
Donepezil Possible antagonism of action
Galantamine Possible antagonism of action
Rivastigmine Possible antagonism of action
Ethotoin The hydantoins may reduce mirtazapine plasma concentrations and pharmacological effects
Fosphenytoin The hydantoins may reduce mirtazapine plasma concentrations and pharmacological effects
Mephenytoin The hydantoins may reduce mirtazapine plasma concentrations and pharmacological effects
Phenytoin The hydantoins may reduce mirtazapine plasma concentrations and pharmacological effects
Fluvoxamine Fluvoxamine increases the effect and toxicity of mirtazapine
Food Interactions: Not Available
Generic Name: Mirtazapine
Synonyms: Mirtazapina [Inn-Spanish]; Mirtazapine [Usan-Ban-Inn]; Mirtazapinum [Inn-Latin]; Mirtazepine; Mepirzepine
Drug Category: Adrenergic alpha-Antagonists; Antidepressive Agents, Tricyclic; Histamine H1 Antagonists
Drug Type: Small Molecule; Approved
Absorption: Rapid and complete, but, due to first-pass metabolism, absolute bioavailability is 50%.
Toxicity (Overdose): Symptoms of overdose include disorientation, drowsiness, impaired memory, and tachycardia. LD50=mg/kg (orally in rat).
Protein Binding: 85%
Biotransformation: Mirtazapine is extensively metabolized by demethylation and hydroxylation followed by glucuronide conjugation. Cytochrome P450 2D6 and cytochrome P450 1A2 are involved in formation of the 8-hydroxy metabolite of mirtazapine, and cytochrome P450 3A4 is responsible for the formation of the N-desmethyl and N-oxide metabolites. Several metabolites possess pharmacological activity, but plasma levels are very low.
Half Life: 20-40 hours
Dosage Forms of Mirtazon: Tablet, orally disintegrating Oral
Chemical IUPAC Name: 1,2,3,4,10,14b-hexahydro-2-methylpyrazino[2,1-a]pyrido[2,3-c]benzazepine
Chemical Formula: C17H19N3
Mirtazapine on Wikipedia: https://en.wikipedia.org/wiki/Mirtazapine
Organisms Affected: Humans and other mammals