Imipramine Pamoate, Tofranil-PM™®

Brand name

  • Tofranil-PM™®

Drug Class

  • Tricyclic Antidepressant (TCA)


  • Capsules 75 mg, 100 mg, 125 mg and 150 mg


  • Major Depression Disorder (MDD)


Mechanism of action:

  • potentiation of adrenergic synapses by blocking uptake of norepinephrine at nerve endings


    • Absorption:
        • Bioavailability: From GI tract (approximately 43%)
        • Peak Plasma Time: within 1–2 hours
        • Onset: within 1–3 weeks
        • Food: does not affect absorptio


    • Distribution
      • Extent:
        • Widely distributed in the body
        • Distributed into milk in concentrations similar to maternal plasma
      • Plasma Protein Binding: 60–96%


    • Metabolism:
      • In the liver by various CYP isoenzymes (CYP1A2, CYP2D6, CYP3A4, CYP2C)
      • Metabolites: Desipramine


    • Elimination:
      • Excretion: principally in urine, small amounts excreted in feces
      • Half-life: 8–20 hours


Initial Adult Dosage:

  • Outpatients:
  • Start dose: 75 mg/day
  • Optimum dose level: 150 mg/day
  • Max dose: 200 mg/day.
  • Hospitalized Patients:
  • Start dose: 100 to 150 mg/day (may be increased to 200 mg/day)
  • Max dose: 250 to 300 mg/day (If there is no response after two weeks)

Adult Maintenance Dosage:

  • Usual dose: 75 to 150 mg/day
  • Following remission for a longer period of time at the lowest dose
  • Should decrease gradually

Adolescent and Geriatric Patients:

  • Start dose: 25 to 50 mg/day (Because Tofranil-PM capsules are not available in these strengths >>> Should be treat with Tofranil-TM, brand of imipramine hydrochloride tablets)
  • Max dose: 100 mg/day


Drug Interactions

  1. Monoamine Oxidase Inhibitors (MAOIs)
  2. Serotonergic Drugs
  3.  Drugs Metabolized by P450 2D6:

Caucasian population: 7% to 10% of Caucasians are “poor metabolizers >>> higher plasma concentrations of tricyclic antidepressants (TCAs)

Certain drugs:

  • Quinidine
  • Cimetidine
  • Phenothiazine
  • Type 1C Anti-arrhythmic (e.g., Propafenone)
  • Flecainide
  • Selective serotonin reuptake inhibitors (SSRIs) (e.g., fluoxetine, sertraline, and paroxetine
  • Hepatic enzyme inhibitors (e.g., cimetidine, fluoxetine)
  • epatic enzyme inducers (e.g., barbiturates, phenytoin)
  • Anticholinergic drugs (including anti-parkinsonism agents)
  • Decongestants and local anesthetic (contain sympathomimetic amine: (e.g., epinephrine, norepinephrine)
  • Anti-hypertension agents
  • CNS depressant

Adverse Effects


Orthostatic hypotension, hypertension, tachycardia, palpitation, myocardial infarction, arrhythmias, heart block, ECG changes, precipitation of congestive heart failure, stroke.


Confusional states (especially in the elderly) with hallucinations, disorientation, delusions; anxiety, restlessness, agitation; insomnia and nightmares; hypomania; exacerbation of psychosis.


Numbness, tingling, paresthesia of extremities; incoordination, ataxia, tremors; peripheral neuropathy; extrapyramidal symptoms; seizures, alterations in EEG patterns; tinnitus.


Dry mouth, and, rarely, associated sublingual adenitis; blurred vision, disturbances of accommodation, mydriasis; constipation, paralytic ileus; urinary retention, delayed micturition, dilation of the urinary tract.


Skin rash, petechiae, urticaria, itching, photosensitization; edema (general or of face and tongue); drug fever; cross-sensitivity with desipramine.


Bone marrow depression including agranulocytosis; eosinophilia; purpura; thrombocytopenia.


Nausea and vomiting, anorexia, epigastric distress, diarrhea; peculiar taste, stomatitis, abdominal cramps, black tongue.


Gynecomastia in the male; breast enlargement and galactorrhea in the female; increased or decreased libido, impotence; testicular swelling; elevation or depression of blood sugar levels; inappropriate antidiuretic hormone (ADH) secretion syndrome.


1- Monoamine Oxidase Inhibitors (MAOIs):

  • Such as linezolid or intravenous methylene blue
  • Contraindicated within 14 days of stopping treatment with Tofranil-PM (increased risk of serotonin syndrome)

2- Myocardial Infarction:

  • Drug is contraindicated during the acute recovery period after a myocardial infarction.

3- Hypersensitivity to Tricyclic Antidepressants


Pregnancy and Breastfeeding

  • Pregnancy: Category D
  • Lactation: not recommended in nursing mothers


1- Clinical Worsening and Suicide Risk:

  • Suicidal ideation and behavior (suicidality):
    • In patients with Major depressive disorder (MDD) and other psychiatric disorders.
    • might persist until significant remission occurs
    • Patients should be supervised during the early phase of treatment (may require hospitalization)
    • Symptoms should be reported to the patient’s prescriber or health professional
    • Occur during early antidepressant treatment and when the dose is adjusted up or down
  • Symptoms:
    • anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia (psychomotor restlessness)
  • Management:
    • close monitoring
    • changes in the medication

2- Dosage administration:

  • Daily dosage could be given as single dose at bedtime
  • Divide dosage schedule (if needed)

3- Antidepressant effect:

  • Might takes one to three weeks

4- ECG should be taken:

  • Prior to the initiation of larger-than-usual doses
  • At appropriate intervals after until steady state is achieved
  • Elderly patients
  • Patients with history of cardiac disease

5- Hypomanic or manic episodes:

  • Occur in patients with cyclic disorders
  • Necessitate discontinuation of the drug. (Drug could be resumed in lower dosage when these episodes are relieved.)
  • Tranquilizer is useful in controlling such episodes.

 6- Activation of the psychosis:

  • Might be observed in schizophrenic patients
  • Require reduction of dosage and the addition of a phenothiazine.

 7- Concurrent use of imipramine pamoate with electroshock therapy:

  • Increase the hazards >>> treatment should be limited

 8- Sunlight exposure:

  • should avoid excessive exposure to sunlight (because of photosensitization)

 9- Blood sugar level:

  • Risk of elevation and lowering of blood sugar levels

 10- Renal and Hepatic impairment:

  • Drug should be used with caution

 11- Pathological Neutrophil Depression:

  • Signs: fever and sore throat during therapy with imipramine pamoate
  • Investigation: leukocyte and differential blood counts
  • Discontinue drug if there is evidence of pathological neutrophil depression.

 12- Prior to elective surgery:

  • Should be discontinued for as long as the clinical situation will allow.

13- Pediatric Use:

  • should not be used in children >>> because of increased potential risk for acute over-dosage

 14- Geriatric Use:

  • Dose selection for the elderly should be cautious >>> starting at the low end of the dosing range

 15- In the case of relapse (due to premature withdrawal of the drug):

  • The effective dosage of imipramine should be reinstituted.

 16- Switching From a Monoamine Oxidase Inhibitor (MAOI) to Imipramine:

  • At least 14 days should elapse

 17- Caution of usage With Other MAOIs (Such as Linezolid or Methylene Blue):

  • Should not start Tofranil-PM in a patient treated with linezolid or intravenous methylene blue >>> because of increasing risk of serotonin syndrome.

 18- Over dose:

  • Manifestations:
    • Symptoms might vary depends on Amount of drug absorbed, Age of the patient, Interval between drug ingestion and treatment.
  • Signs and symptoms:
    • Critical manifestations: Cardiac Dysrhythmias, Severe Hypotension, Convulsions, CNS Depression, Coma
  • Toxicity indicator:
    • Changes in the electrocardiogram (particularly in QRS axis or width)
  • Management
    • No specific antidote
    • Supportive therapy

 19- Withdrawal Symptoms:

  • Abrupt cessation may produce nausea, headache and malaise.



This document is prepared by the “Mental Health for All” team. This document is provided for information purposes only and does not necessarily represent endorsement by or an official position of the Essentials of Medicine. Advice on the treatment or care of an individual patient should be obtained through consultation with a physician who has examined that patient or is familiar with that patient’s medical history.

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