Drug Interaction:
        
        
            
	Tetracyclic antidepressants  include - Mirtazapine and Maprotiline, Mianserin
	 
	Refer  - Mitrazapine
	 
	Drug interactions - summary
	 
	 Alcohol + tetracyclic antidepress  
	 Advice patients to avoid alcohol while taking mirtazapine
	   
	Anticholinergics (hyocyamine, Scopolamine + Tetracyclic antidep Maprotaline
	Additive atropine -like effects may occur. 
	 
	Benzodiazepine ( Diazepam ) + tetracyclic antidep / Tetracyclic antidep + Benzodiazepine
	Additive impairment of motor skills . Advice patients to avoid Diazepam and similar drugs    
	 Advise patients to avoid diazepam and other similar drugs
	 
	Cisapride  + Tetracyclic antidepress. Maprotaline/ Tetracyclic antidep + Cisapride
	Co-administeration is contraindicated
	  
	CYP inducers ( barbiturates, phenytoin )  + Tetracyclic antidepess 
	Plasma conc. of  maprotiline decreased
	         
	CYP inhibitors ( cimetidine, fluoxetine ) + Tetracyclic antidepress 
	Plasma conc.of maprotiline increased
	                                    
	PhMAOIs ( phenelzine, selegiline )  + tetracyclic Antidepress or Tetracyclic antidep + MAOIs- Phenelzine-
	Concomittant use of maprotoline with an MAOI  is  contraindicated. 
	Allow  14 days period after  discontinuing an MAOI  & before initiating maprotiline.
	 
	Phenothiazine ( chlorpropazine, Thioridazinene )+ Tetracyclic antidepress. Maprotaline  
	Risk of seizures ncreased with concomittant  use
	                        
	SSRIs ( fluvoxetine, fluvoamine)  + Tetracyclic antidepress Mitrazapine  
	Increase in  mitazapine in serum levels after fluvoamine  was added  to treatment 
	Adjust mirtazapine dose
	                                                                                             
	Sympathomimetics  (epinehrine) + Tetracyclic Antidepress. Maprotaline/  Maprotaline + Epinephrine
	Closely supervise and carefully adjust dosage   when coadministering  maprotiline        
	 
	 
	Tetracyclic antidepress- maprotiline  + Guanitthidine 
	Maprotiline may block the pharmacologic effects of   guanithidine or similar drugs
	 
	Tetracyclic antidepress- maprotiline  + Thyroid hormones Levothyroxine 
	Use caution when administering maprotiline to   hypothroid patients and those receiving medication
	                                                                             
        
     
    
    
           
            Indication:
        
        
            
	Major depressive disorder 
	 
	Approved by (DCI) Drug Controller  GENERAL -  India  For Marketing
	                                                                                   (Ref- IDMA Publication)
	 
	Name of Drug                   Indication                             Date of Approval
	 
	Mirtrazapine                       Anti depresant                    14-02-2001
	 
	 
	 
	Patent Expiry Date of drugs (Ref - IDMA Publication)    
	 
	Chemical       Category                      Manufacturer/        US Patent
	Ingredient-                                           Marketer                   Expiration Date  
	 
	Mirtrazapine    CNS                            Akzo Nobel NV        14-06-2001
	Tetracyclic antidepressants include -
	Mirtazapine and Maprotiline, Mianserin
	Refer - Mitrazapine 
        
     
    
    
           
            Adverse Reaction:
        
        
            
	Adverse Reactions-
	
	MIRTAZIPINE -
	-------------------
	CARDIOVASCULAR - 
	  Hypertension > 1% Hypotension  1%
	CNS-     
	 Somnolence 54%Dizziness 7%  Asthenia 8%  Abnormal dreams 4%
	  Abnormal thinking 3%  Tremor 2% Agitation 1%  Anxiety 1%
	DERMATOLOGIC -
	Alopecia  1%,Rash 1%  
	GI-
	 Dry mouth 25%  Increased appetite 17%Constipation 13%  Nausea  >1%
	 Nausea and vomiting 1%
	METABOLIC/NUTRIONAL -
	Peripheral edema 2%  Edema 1%  Weight gain 12% Weight loss 1%
	MISCELLANEOUS -
	 Flu syndrome 5% Myalgia 2%    Back pain 2% Urinary frequency 2%
	  Altered liver function 1% Dyspnea 1%
	 
        
     
    
    
           
            Contra-Indications:
        
        
            
	Hypersensitivity to Maprotiline
	 Maprotiline - known or seizure disorder
	Use during acute phase of myocardial infarction MI ,
	Co-adminstration with MAOI inhibitors
	Special precautions- 
	Clinical worsening of suicide risk - Adults and children with MDD may experience of worsening of their depression and/or emergence of suicidal ideation and behaviour or unusual changes in behaviour
	Consider changing the therapeuticc regimen including possibly of discontinuing the medication in patients whose depression is persistently worse
	Seizures- have been associated with the use of maprotiline.
	Risk of seizure may be increased when meprotiline is taken concomittantly with phenothiazines, when the dosage is rapidly tapered in patients receiving maprotiline. The risk can be reduced by initiating therapy at a low dose, maintain the initial dose for 2 weeks and raising it gradually as needed
	MAOIs - concomittant use of maprotiline with an MAOI is contraindicated
	Renal/hepatic function impairment- caution must be excercised when administering mirtazapine to such patients
	Special risk patients- Administer maprotiline with caution in patients with increased intraocular pressure, history of urinary retention, or history of narrow angle glaucoma because of the drugs anticholinergic properties
	Pregnancy- Use the drug during pregnancy only if clearly needed Labor and delivery. As with any other CNS depedent drugs excercise caution during labor and delivery
	Lactation- Excercise caution when maprotiline is administered to a breast feeding woman.
	Children - safety for use in children have not been established
	Elderly- excecise caution when administering mitrazapine to elderly patients
        
     
    
    
           
            Dosages/ Overdosage  Etc:
        
        
            
	Date of Approval    2001
	Indication
	Major depressive disorder
	Dosage-
	Maximum dose 45mg/day
	Iinitial - 15mg/day as a single dose preferably in the evening prior to sleep. The effective dose range is generally 15 to 45mg/day Patients not responding to initial dose of 15mg/day may benefit from dose increases of up to 45mg/day
        
     
    
    
           
            Patient Information:
        
        
            
	Tetracyclic antidepressants includes
	- Mirtazapine and Maprotiline, Mianserin
	Refer - Mitrazapine 
	1. Clinical worsening and suicide risk- Advice families to observe for the emergence of suicidal symptoms/ tendency on a daily basic and report such symptoms to your doctor
	2. Hazardous tasks- caution patients about engaging inhazardous activites until they are re resonably certain that tetracyclics do not adversely affect their ability to engage in such activites
	3. Alcohol- advice patients to avoid alcohol while taking tetracyclic antidepressants becuase of aditive impairment of cognitive and motor skills
	4. Pregnancy and breast feeding- advice patients to notify their doctor if thet become pregnant or intend to become pregnant or are breast feeding during tetracyclic therapy
        
     
    
    
           
            Pharmacology/ Pharmacokinetics:
        
        
            
	Pharmacology- 
	The mechanism of action of tetracyclic is not precisely known. Maprotiline and mirtazapine are both considered tetracyclic antidepressants ( because of their chemical structure ), but they each affect different neurotransmitters and thus have different adverse reaction profiles
	Maprotiline primarily acts by potentiation of central adrenergic synapses by blocking reuptake of noreppinephrine at nerve endings. This pharmacologic action is thought to be responsible for its antidepressant and anxiolytic effects.
	Absoption/distribution-
	Maprotiline is slowly and completely absorbed after oral admiin. and steady state is acheived after 1 week. of therapy Mirtazapine tablets are rapidly and completely absorbed following oral admin.
	Presence of food in the stomach has a minimal effect in the rate and extent of absorption and does not require dose adjustment Maprotiline is slowly eliminated primarily as metobolites ( most of which are glucoronides )
	Mirtazapine is extensively matabolised after oral admin.
        
     
    
    
           
            Interaction with Food:
        
        
            
	Presence of food has a minmal effect on the rate and extent of absorption
        
     
    
    
           
            Pregnancy and lactation:
        
        
            
	Pregnancy- 
	Use the drug during pregnancy only if clearly needed Labor and delivery- as with any other CNS depedent drugs excercise caution during labor and delivery
	Lactation-
	Excercise caution when maprotiline is administered to a breast feeding woman.
	Children -
	Safety for use in children have not been established
	Elderly-
	excecise caution when administering mitrazapine to elderly patients