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