Impril


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imipramine

(im-ip-ra-meen) ,

Impril

(trade name),

Tofranil

(trade name),

Tofranil PM

(trade name)

Classification

Therapeutic: antidepressants
Pharmacologic: tricyclic antidepressants
Pregnancy Category: C

Indications

Various forms of depression.Enuresis in children.Adjunct in the management of chronic pain, incontinence (in adults), vascular headache prophylaxis, cluster headache, insomnia.

Action

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

Therapeutic effects

Antidepressant action that develops slowly over several weeks.

Pharmacokinetics

Absorption: Well absorbed from the GI tract.
Distribution: Widely distributed. Probably crosses the placenta and enters breast milk.
Protein Binding: 89–95%.
Metabolism and Excretion: Mostly metabolized by the liver (CYP2D6 isoenzyme) to desipramine;genetic implication the CYP2D6 enzyme system exhibits genetic polymorphism; ∼7% of population may be poor metabolizers (PMs) and may have significantly ↑ imipramine concentrations and an ↑ risk of adverse effects.
Half-life: 8–16 hr.

Time/action profile (antidepressant effect)

ROUTEONSETPEAKDURATION
POhours2–6 wkweeks

Contraindications/Precautions

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 QTc interval prolongation, heart failure;Concurrent use of MAO inhibitors or MAO-like drugs (linezolid or methylene blue).
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; Lactation: Drug is present in breast milk; discontinue imipramine or bottle feed; Pediatric: Suicide risk may be greater in children or adolescents. Safety not established in children <6 yr; Geriatric: More susceptible to adverse reactions. Geriatric males with prostatic hyperplasia are more susceptible to urinary retention.

Adverse Reactions/Side Effects

Central nervous system

  • suicidal thoughts (life-threatening)
  • drowsiness (most frequent)
  • fatigue (most frequent)
  • agitation
  • confusion
  • hallucinations
  • insomnia

Ear, Eye, Nose, Throat

  • blurred vision (most frequent)
  • dry eyes (most frequent)

Cardiovascular

  • arrhythmias (life-threatening)
  • hypotension (most frequent)
  • ECG changes

Gastrointestinal

  • constipation (most frequent)
  • dry mouth (most frequent)
  • nausea
  • paralytic ileus
  • weight gain

Genitourinary

  • urinary retention
  • ↓ libido

Dermatologic

  • photosensitivity

Endocrinologic

  • gynecomastia

Hematologic

  • blood dyscrasias

Interactions

Drug-Drug interaction

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 SSRI antidepressants may result in ↑ toxicity and should be avoided (fluoxetine should be stopped 5 wk before).Hypertensive crisis may occur with clonidine.Imipramine is metabolized in the liver by the cytochrome P450 2D6 enzyme and its action may be affected by drugs that compete for metabolism by this enzyme including otherantidepressants, phenothiazines, carbamazepine, class 1Cantiarrhythmics (propafenone, flecainide ); when used concurrently, dose reduction 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.Use with St. John's wort ↑ of serotonin syndrome.Concomitant use of kava-kava, valerian, or chamomile can ↑ CNS depression.↑ anticholinergic effects with jimson weed and scopolia.

Route/Dosage

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

Availability (generic available)

Tablets: 10 mg, 25 mg, 50 mg, 75 mg
Capsules: 75 mg, 100 mg, 125 mg, 150 mg

Nursing implications

Nursing assessment

  • Monitor BP and pulse rate prior to and during initial therapy.
  • Monitor plasma levels in treatment-resisant patients.
  • Monitor weight and BMI initially and periodically throughout therapy.
  • For overweight/obese individuals, obtain FBS and cholesterol levels. Refer as appropriate for nutrition/weight management and medical management.
  • Obtain weight and BMI initially and regularly throughout therapy.
  • Assess for sexual dysfunction (decreased libido; erectile dysfunction).
  • Assess for suicidal tendencies, especially during early therapy. Restrict amount of drug available to patient. Risk may be increased in children, adolescents, and adults ≤24 yrs. After starting therapy, children, adolescents, and young adults should be seen by health care professional at least weekly for 4 wk, every 3 wk for next 4 wk, and on advice of health care professional thereafter.
  • Pediatric / Geriatric: Monitor baseline and periodic ECGs in elderly patients or patients with heart disease and before increasing dose with children treated for enuresis. May cause prolonged PR and QT intervals and may flatten T waves.
  • Depression: Assess mental status (orientation, mood, behavior) frequently. Confusion, agitation, and hallucinations may occur during initiation of therapy and may require dosage reduction. Assess for suicidal tendencies, especially during early therapy. Restrict amount of drug available to patient.
  • Enuresis: Assess frequency of bedwetting during therapy. Ask patient or caretaker to maintain diary.
  • Pain: Assess location, duration, and severity of pain periodically during therapy. Use pain scale to monitor effectiveness of therapy.
  • Lab Test Considerations: Assess leukocyte and differential blood counts and renal and hepatic functions prior to and periodically during prolonged or high-dose therapy.
    • Serum levels may be monitored in patients who fail to respond to usual therapeutic dose. Therapeutic plasma concentration range for depression is 150–300 ng/mL.
    • May cause alterations in blood glucose levels.
  • Symptoms of acute overdose include disturbed concentration, confusion, restlessness, agitation, seizures, drowsiness, mydriasis, arrhythmias, fever, hallucinations, vomiting, and dyspnea.
    • Treatment of overdose includes gastric lavage, activated charcoal, and a stimulant cathartic. Maintain respiratory and cardiac function (monitor ECG for at least 5 days) and temperature. Medications may include digoxin for HF, antiarrhythmics, and anticonvulsants.

Potential Nursing Diagnoses

Ineffective coping (Indications)
Impaired urinary elimination (Indications,  Side Effects)
Sexual dysfunction (Side Effects)

Implementation

  • Dose increases should be made at bedtime because of sedation. Dose titration is a slow process; may take weeks to months. May be given as a single dose at bedtime to minimize sedation during the day.
    • Taper to avoid withdrawal effects. Reduce by 50% for 3 days, then reduce by 50% for 3 days, then discontinue.
  • Oral: Administer medication with or immediately following a meal to minimize gastric irritation.
  • Intramuscular: May be slightly yellow or red in color. Crystals may develop if solution is cool; place ampule under warm running water for 1 min to dissolve.

Patient/Family Teaching

  • 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 female patients to notify health care professional if pregnancy is planned or suspected, or if breast feeding.
  • Pediatric: 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.

Evaluation/Desired Outcomes

  • Increased sense of well-being.
    • Renewed interest in surroundings.
    • Increased appetite.
    • Improved energy level.
    • Pain relief.
    • Diminished incidence of enuresis.
    • Improved sleep in patients treated for depression. Patient may require 2–6 wk of therapy before full therapeutic effects of medication are noticeable.
  • Control of bedwetting in children >6 yr.
  • Decrease in chronic neurogenic pain.

Impril

Imipramine, see there.