• Major depressive disorder.
• Enuresis in children.

Unlabeled Uses:

• Adjunct in the management of chronic pain, incontinence (in adults), vascular headache prophylaxis, cluster headache, insomnia.

Contraindicated in:

• Hypersensitivity
• Cross-sensitivity with other antidepressants may occur
• Angle-closure glaucoma
• Hypersensitivity to tartrazine or sulfites (in some preparations)
• Recent MI, known history of QT interval prolongation, HF
• Concurrent use of MAO inhibitors or MAO-like drugs (linezolid or methylene blue)
• Lactation: Lactation.

Use Cautiously in:

• Pre-existing cardiovascular disease
• Seizures or history of seizure disorder
• May ↑ risk of suicide attempt/ideation especially during early treatment or dose adjustment
• OB: Use during pregnancy only if potential maternal benefit justifies potential fetal risk
• Pedi: Suicide risk may be greater in children or adolescents. Safety and effectiveness not established in children <6 yr
• Geri: Appears on Beers list. ↑ risk of adverse reactions in older adults, including falls secondary to sedative and anticholinergic effects and orthostatic hypotension. Avoid use in older adults.

CV: hypotension, ARRHYTHMIAS, ECG changes.

Derm: photosensitivity.

EENT: blurred vision, dry eyes.

Endo: gynecomastia.

GI: constipation, dry mouth, nausea, paralytic ileus.

GU: ↓libido, urinary retention.

Hemat: blood dyscrasias.

Metab: weight gain.

Neuro: drowsiness, fatigue, agitation, confusion, hallucinations, insomnia, SUICIDAL THOUGHTS.

Drug-Drug:

• Concurrent use with MAO inhibitors may result in serious potentially fatal reactions (MAO inhibitors should be stopped at least 14 days before imipramine therapy. Imipramine should be stopped at least 14 days before MAO inhibitor therapy).
• Concurrent use with MAO-inhibitor like drugs, such as linezolid or methylene blue, may ↑ risk of serotonin syndrome; concurrent use contraindicated; do not start therapy in patients receiving linezolid or methylene blue; if linezolid or methylene blue need to be started in a patient receiving imipramine, immediately discontinue imipramine and monitor for signs/symptoms of serotonin syndrome for 2 wk or until 24 hr after last dose of linezolid or methylene blue, whichever comes first (may resume imipramine therapy 24 hr after last dose of linezolid or methylene blue)
• Concurrent use with SSRIs may result in ↑ toxicity and should be avoided (fluoxetine should be stopped 5 wk before starting imipramine).
• Hypertensive crisis may occur with clonidine.
• Imipramine is metabolized in the liver by the CYP2D6 isoenzyme and its action may be affected by drugs that compete for metabolism by this enzyme including other antidepressants, phenothiazines, carbamazepine, class IC antiarrhythmics (propafenone, flecainide); when used concurrently, dose ↓ of one or the other or both may be necessary. Concurrent use of other drugs that inhibit the activity of the enzyme, including cimetidine, quinidine, amiodarone, and ritonavir, may result in ↑ effects of imipramine.
• Concurrent use with levodopa may result in delayed/↓ absorption of levodopa or hypertension.
• Blood levels and effects may be ↓ by rifamycins.
• ↑CNS depression with other CNS depressants including alcohol, antihistamines, clonidine, opioids, and sedative/hypnotics.
• Barbiturates may alter blood levels and effects.
• Adrenergic and anticholinergic side effects may be ↑ with other agents having these properties.
• Phenothiazines or hormonal contraceptives↑ levels and may cause toxicity.
• Cigarette smoking(nicotine) may ↑ metabolism and alter effects.
• Drugs that affect serotonergic neurotransmitter systems, including SSRIs, SNRIs, fentanyl, buspirone, tramadol, and triptans↑ risk of serotonin syndrome.

Drug-Natural Products:

• Use with St. John's wort↑ risk of serotonin syndrome.
• Concomitant use of kava-kava, valerian, or chamomile can ↑ CNS depression.
• ↑anticholinergic effects with jimson weed and scopolia.

(Generic available)

• Tablets: 10 mg; 25 mg; 50 mg; 75 mg;
• Capsules: 75 mg; 100 mg; 125 mg; 150 mg;

Major Depressive Disorder

• PO (Adults): 25–50 mg 3–4 times daily (not to exceed 300 mg/day); total daily dose may be given at bedtime.
• PO (Geriatric Patients): 25 mg at bedtime initially, up to 100 mg/day in divided doses.
• PO (Children >12 yr): 25–50 mg/day in divided doses (not to exceed 100 mg/day).
• PO (Children 6–12 yr): 10–30 mg/day in 2 divided doses.

Enuresis

• PO (Children 6 yr): 25 mg once daily 1 hr before bedtime; ↑ if necessary by 25 mg at weekly intervals to 50 mg in children <12 yr, up to 75 mg in children >12 yr.

Tofranil

• Potentiates the effect of serotonin and norepinephrine.
• Has significant anticholinergic properties.

• Antidepressant action that develops slowly over several weeks.
• Diminished incidence of enuresis.

Therapeutic Classification: antidepressants

Pharmacologic Classification: tricyclic antidepressants

Absorption: Well absorbed from the GI tract.

Distribution: Widely distributed to tissues.

Protein Binding: 89–95%.

Metabolism/Excretion: Mostly metabolized by the liver (CYP2D6 isoenzyme) to desipramine;the CYP2D6 enzyme system exhibits genetic polymorphism; 7% of population may be poor metabolizers and may have significantly ↑ imipramine concentrations and an ↑ risk of adverse effects.

Half-life: 8–16 hr.

(antidepressant effect)

• Instruct patient to take medication as directed. Take missed doses as soon as possible unless almost time for next dose; if regimen is a single dose at bedtime, do not take in the morning because of side effects. Advise patient that drug effects may not be noticed for at least 2 wk. Abrupt discontinuation may cause nausea, vomiting, diarrhea, headache, trouble sleeping with vivid dreams, and irritability.
  • May cause drowsiness and blurred vision. Caution patient to avoid driving and other activities requiring alertness until response to drug is known.
  • Instruct patient to notify health care professional if visual changes occur. Inform patient that periodic glaucoma testing may be needed during long-term therapy.
  • Caution patient to change positions slowly to minimize orthostatic hypotension.
  Advise patient, family, and caregivers to look for suicidality, especially during early therapy or dose changes. Notify health care professional immediately if thoughts about suicide or dying, attempts to commit suicide, new or worse depression or anxiety, agitation or restlessness, panic attacks, insomnia, new or worse irritability, aggressiveness, acting on dangerous impulses, mania, or other changes in mood or behavior or if symptoms of serotonin syndrome occur.
  • Advise patient to avoid alcohol or other CNS depressant drugs during therapy and for at least 3–7 days after therapy has been discontinued.
  • Instruct patient to notify health care professional if urinary retention, dry mouth, or constipation persists. Sugarless candy or gum may diminish dry mouth and an increase in fluid intake or bulk may prevent constipation. If symptoms persist, dose reduction or discontinuation may be necessary. Consult health care professional if dry mouth persists for more than 2 wk.
  • Caution patient to use sunscreen and protective clothing to prevent photosensitivity reactions.
  • Alert patient that urine may turn blue-green in color.
  • Inform patient of need to monitor dietary intake, as possible increase in appetite may lead to undesired weight gain. Inform patient that increased amounts of riboflavin in the diet may be required; consult health care professional.
  • Advise patient to notify health care professional of medication regimen prior to treatment or surgery.
  • Therapy for depression is usually prolonged. Emphasize the importance of follow-up exams to evaluate progress and improve coping skills.
• Instruct females of reproductive potential to notify health care professional if pregnancy is planned or suspected, and to avoid breastfeeding.
• Pedi: Inform parents that the side effects most likely to occur include nervousness, insomnia, unusual tiredness, and mild nausea and vomiting. Notify health care professional if these symptoms become pronounced.
  • Advise parents to keep medication out of reach of children to prevent inadvertent overdose.

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