trimipramine

Absorption: Well absorbed following oral administration.

Distribution: Unknown.

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

Half-Life: 7–30 hr.

Time/Action Profile ⬆ ⬇

ROUTE	ONSET	PEAK	DURATION
PO	2–3 wk (up to 30 days)	2–6 wk	days–wks

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity; cross-sensitivity may occur with other tricyclic antidepressants;
Recovery phase following MI;
Concurrent use of MAO inhibitors or MAO-like drugs (linezolid or methylene blue);
Angle-closure glaucoma.

Use Cautiously in:

History of or symptoms compatible with bipolar disease (may precipitate mixed/manic episodes;
May ↑ risk of suicide attempt/ideation especially during early treatment or dose adjustment; risk may be greater in children and adolescents;
Prostatic hyperplasia (↑ risk of urinary retention);
History of seizures (may ↓ threshold);
Hepatic impairment;
Electroshock therapy (may ↑ risk of adverse reactions);
↑intraocular pressure;
Hyperthyroidism (↑ risk of cardiovascular toxicity);
OB: Safety not established in pregnancy;
Lactation: Safety not established in breastfeeding;
Pedi: Safety and effectiveness not established in children;
Geri: risk of adverse reactions in older adults, including falls secondary to sedative and anticholinergic affects.

Pre-existing cardiovascular disease.

Adv. Reactions/Side Effects ⬆ ⬇

CV: ARRHYTHMIAS, hypotension, ECG changes

Derm: photosensitivity.

EENT: blurred vision, dry eyes, dry mouth

Endo: changes in blood glucose , gynecomastia

GI: constipation , hepatitis, paralytic ileus

GU: ↓libido, urinary retention,

Hemat: blood dyscrasias

Metab: ↑appetite , weight gain.

Neuro: lethargy, sedation.

Interactions ⬆ ⬇

Drug-drug:

Concurrent use with MAO inhibitors may result in serious, potentially fatal reactions. (MAO inhibitors should be stopped at least 14 days before trimipramine therapy. Trimipramine 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 trimipramine, immediately discontinue trimipramine 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 trimipramine therapy 24 hr after last dose of linezolid or methylene blue).
Trimipramine 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 other antidepressants, phenothiazines, carbamazepine, class 1C antiarrhythmics including propafenone, and flecainide; when used concurrently, dose adjustment 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 trimipramine.
Concurrent use with SSRIs may result in toxicity and should be avoided (fluoxetine should be stopped 5 wk before starting trimipramine).
Concurrent use with clonidine may result in hypertensive crisis and should be avoided.
Concurrent use with levodopa may result in delayed or absorption of levodopa or hypertension.
Blood levels and effects may be ↓ by rifampin, rifapentine, and rifabutin.
Concurrent use with moxifloxacin↑ risk of adverse cardiovascular reactions.
↑CNS depression with other CNS depressants, including alcohol, antihistamines, clonidine, opioids, and sedative/hypnotics.
Barbiturates may alter levels and effects.
↑adrenergic and anticholinergic side effects with other agents having adrenergic or anticholinergic properties.
Levels and risk of toxicity may be ↑ by phenothiazines or oral contraceptives.
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↑ of serotonin syndrome.
Concomitant use of kava-kava, valerian, or chamomile can ↑ CNS depression.
↑anticholinergic effects with jimson weed and scopolia.

Route/Dosage ⬆ ⬇

PO (Adults ): 75 mg/day in divided doses or as a single daily dose at bedtime; may be ↑ up to 150 mg/day; not to exceed 200 mg/day (300 mg/day in hospitalized patients).
PO Geriatric Patients ): 50 mg/day, may gradually ↑ up to 100 mg/day.

Availability ⬆ ⬇

(Generic available)

Capsules: 25 mg; 50 mg; 75 mg; 100 mg
Tablets: 12.5 mg; 25 mg; 50 mg; 100 mg

Assessment ⬆ ⬇

Monitor BP and pulse before and during initial therapy. Notify health care professional of decreases in BP (10–20 mmHg) or sudden increase in pulse rate. Patients taking high doses or with a history of cardiovascular disease should have ECG monitored before and periodically during therapy.
Geri: Geriatric patients started on trimipramine may be at an increased risk for falls; start with low dose and monitor closely.
Depression: Monitor mental status and affect. 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 yr. 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. Assess for bipolar disorder; onset may mimic depression and trimipramine is not approved for treatment of bipolar disorder.
Assess for serotonin syndrome (mental changes [agitation, hallucinations, coma], autonomic instability [tachycardia, labile BP, hyperthermia], neuromuscular aberrations [hyperreflexia, incoordination], and/or GI symptoms [nausea, vomiting, diarrhea]), especially in patients taking other serotonergic drugs (SSRIs, SNRIs, triptans).

Lab Test Considerations:

Assess leukocyte and differential blood counts, liver function, and serum glucose before and periodically during therapy. May ↑ serum bilirubin and alkaline phosphatase. May cause bone marrow depression. Serum glucose may be ↑ or ↓.

Implementation ⬆ ⬇

Dose increases should be made at bedtime because of sedation. Dose titration is a slow process; may take wk to mo. May give entire dose at bedtime. Sedative effect may be apparent before antidepressant effect is noted.
PO: Administer without regards to food.

Patient/Family Teaching ⬆ ⬇

Instruct patient to take medication as directed. Take missed doses as soon as possible unless almost time for next dose. Advise patient that drug effects may not be noticed for at least 2 wk. Do not discontinue without consulting health care professional. Abrupt discontinuation may cause nausea, vomiting, diarrhea, headache, trouble sleeping with vivid dreams, and irritability. Instruct patient to read Medication Guide prior to starting therapy and with each Rx refill in case of changes.
May cause drowsiness and blurred vision. Caution patient to avoid driving and other activities requiring alertness until response to drug is known.
Orthostatic hypotension, and sedation are common during early therapy, especially in geriatric patients. Protect patient from falls and advise patient to make position changes slowly.
Advise patient to avoid alcohol or other CNS depressant drugs during and for 3–7 days after therapy has been discontinued.
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.
Instruct patient to notify health care professional if urinary retention occurs or if 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.
Inform patient of need to monitor dietary intake. Increase in appetite may lead to undesired weight gain.
Advise patient to notify health care professional of medication regimen before treatment or surgery. Medication should be discontinued as long as possible before surgery.
Rep: Advise females of reproductive potential to notify health care professional if pregnancy is planned or suspected or if breastfeeding.
Therapy for depression is usually prolonged and should be continued for at least 3 mo to prevent relapse. Emphasize the importance of follow-up exams to monitor effectiveness and side effects.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇