IMIPRAMINE HYDROCHLORIDE

(im-ip'ra-meen)

Impril

, Novopramine

, Tofranil
IMIPRAMINE PAMOATE
Tofranil-PM
Classifications: psychotherapeutic; tricyclic antidepressant;
Therapeutic: tricyclic antidepressant
Pregnancy Category: C

Availability

10 mg, 25 mg, 50 mg tablets; 75 mg, 100 mg, 125 mg, 150 mg capsules

Imipramine pamoate:75 mg, 100 mg, 125 mg, 150 mg capsules

Action

Tricyclic antidepressant (TCA) and tertiary amine, structurally related to the phenothiazines. In contrast with phenothiazines that act on dopamine receptors, TCAs potentiate both norepinephrine and serotonin in the CNS by blocking their reuptake by presynaptic neurons. Imipramine decreases number of awakenings from sleep, markedly reduces time in REM sleep, and increases stage 4 sleep.

Therapeutic Effect

As a TCA antidepressant, imipramine potentiates the effects of both norepinephrine and serotonin in the CNS by blocking their reuptake by the neurons. Relief of nocturnal enuresis is due to anticholinergic activity and to nervous system stimulation, resulting in earlier arousal to sensation of full bladder.

Uses

Endogenous depression and occasionally for reactive depression. Imipramine is the only TCA used as temporary adjuvant treatment of enuresis in children >6 y.

Unlabeled Uses

Certain syndromes that mimic or overlap diagnostically with depression: alcoholism, cocaine withdrawal; attention deficit disorder with or without hyperactivity (children >6 y and adolescents); with amphetamines or methylphenidate for narcolepsy; phobic anxiety syndromes such as panic disorders and agoraphobia; obsessive-compulsive neurosis; chronic intractable pain.

Contraindications

Hypersensitivity to tricyclic drugs; concomitant use of MAOIs; acute recovery period after MI, defects in bundle-branch conduction, QT prolongation; severe renal or hepatic impairment; use of imipramine HCl in children <12 y except to treat enuresis; use of pamoate in children of any age; pregnancy (category D), lactation.

Cautious Use

Children, adolescents, older adults; respiratory difficulties; cardiovascular, hepatic, or GI diseases; blood disorders; increased intraocular pressure, narrow-angle glaucoma; schizophrenia, hypomania or manic episodes, patient with suicidal tendency, seizure disorders; prostatic hypertrophy, urinary retention; alcoholism, hyperthyroidism; electroshock therapy.

Route & Dosage

Depression
Adult: PO 75–100 mg/d (max: 300 mg/d) in 1 or more divided doses IM 50–100 mg/d in divided doses
Child: PO 1.5 mg/kg/d, may increase by 1 mg/kg/d q3–4d (max: 5 mg/kg/d)

Enuresis in Childhood
Child: PO 25 mg 1 h before bedtime; <12 y, may increase to 50 mg nightly (max: 2.5 mg/kg); >12 y, may increase to 75 mg nightly (max: 2.5 mg/kg)

Administration

Oral

Do NOT make dosage adjustments more frequently than q4d.
Give with or immediately after food.
Note: Single doses can be given h.s. or q.a.m., respectively, if drowsiness or insomnia results.

Intramuscular

Use IM form only for those unable/unwilling to take oral form.
Dissolve crystals by immersing intact ampule in warm water for about 1 min.

Adverse Effects (≥1%)

Body as a Whole: Hypersensitivity (skin rash, erythema, petechiae, urticaria, pruritus, photosensitivity, angioedema of face, tongue, or generalized; drug fever). CNS: Sedation, drowsiness, dizziness, headache, fatigue, numbness, tingling (paresthesias) of extremities; incoordination, ataxia, tremors, peripheral neuropathy, extrapyramidal symptoms (including parkinsonism effects and tardive dyskinesia); lowered seizure threshold, altered EEG patterns, delirium, disturbed concentration, confusion, hallucinations, anxiety, nervousness, insomnia, vivid dreams, restlessness, agitation, shift to hypomania, mania; exacerbation of psychoses; hyperpyrexia. CV: Orthostatic hypotension, mild sinus tachycardia; arrhythmias, hypertension or hypotension, palpitation, MI, CHF, heart block, ECG changes, stroke, flushing, cold cyanotic hands and feet (peripheral vasospasm). Endocrine: Testicular swelling, gynecomastia (men), galactorrhea and breast enlargement (women), increased or decreased libido, ejaculatory and erectile disturbances, delayed or absent orgasm (male and female); elevation or depression of blood glucose levels. Special Senses: Nasal congestion, tinnitus; blurred vision, disturbances of accommodation, slight mydriasis, nystagmus. GI: Dry mouth, constipation, heartburn, excessive appetite, weight gain, nausea, vomiting, diarrhea, slowed gastric emptying time, flatulence, abdominal cramps, esophageal reflux, anorexia, stomatitis, increased salivation, black tongue, peculiar taste, paralytic ileus. Urogenital: Urinary retention, delayed micturition, nocturia, paradoxic urinary frequency. Hematologic: Bone marrow depression; agranulocytosis, eosinophilia, thrombocytopenia. Other: Excessive perspiration, cholestatic jaundice, precipitation of acute intermittent porphyria; dyspnea, changes in heat and cold tolerance, hair loss, syndrome of inappropriate antidiuretic hormone secretion (SIADH).

Diagnostic Test Interference

Imipramine elevates serum bilirubin, alkaline phosphatase and may increase or decrease blood glucose. It decreases urinary 5-HIAA and VMA excretion and may falsely increase excretion of urinary catecholamines.

Interactions

Drug: mao inhibitors may precipitate hyperpyrexic crisis, tachycardia, or seizures; antihypertensive agents potentiate orthostatic hypotension; cns depressants, alcohol add to CNS depression; norepinephrine and other sympathomimetics may increase cardiac toxicity; cimetidine decreases hepatic metabolism, thus increasing imipramine levels; methylphenidate inhibits metabolism of imipramine and thus may increase its toxicity. Herbal: Ginkgo may decrease seizure threshold; St. John's wort may cause serotonin syndrome.

Pharmacokinetics

Absorption: Completely absorbed from GI tract. Peak: 1–2 h PO; 30 min IM. Metabolism: Metabolized to the active metabolite desipramine in liver. Elimination: Primarily in urine, small amount in feces; crosses placenta; may be secreted in breast milk. Half-Life: 8–16 h.

Nursing Implications

Assessment & Drug Effects

Monitor for therapeutic effectiveness: May not occur for 2 wk or more.
Monitor children and adolescents for increase in suicidality.
Prevent serious adverse effects by accurate early reporting to physician about patient's response to drug.
Note: Dose sensitivity and adverse effects are most likely to occur in adolescents and older adults; use a lower initial dose in these patients.
Lab tests: Monitor hepatic and renal function, CBC with differential, and fluid and electrolyte balance periodically.
Monitor HR and BP frequently. Orthostatic hypotension may be marked in pretreatment hypertensive or cardiac patients.
Monitor for potential signs of toxicity: QRS prolongation (to 100 millisecond or greater), arrhythmias, hypotension, respiratory depression, altered level of consciousness, seizures. Overdose onset may be sudden.
Note: During the first 2 wk of therapy, older adults may develop confusion, restlessness, disturbed sleep, forgetfulness. Symptoms last 3–20 d. Report to physician.
Weigh patient under standard conditions biweekly: report a gain of 0.5–1.0 kg (1?–2 lb) within 2–3 d and frank edema.
Monitor urinary and bowel elimination, at least until maintenance dosage is stabilized, to detect urinary retention or frequency, constipation, or paralytic ileus.
Report promptly early signs of agranulocytosis (see Appendix F).
Report signs of cholestatic jaundice: flu-like symptoms, yellow skin or sclerae, dark urine, light-colored stools, pruritus.
Notify physician of extrapyramidal symptoms (tremors, twitching, ataxia, incoordination, hyperreflexia, drooling) in patients receiving large doses and especially in older adults.
Monitor diabetic patients for loss of glycemic control. Hyperglycemia or hypoglycemia (see Appendix F) occur in some patients.
Inspect oral mucosa frequently, especially gingival surfaces under dentures.

Patient & Family Education

Change position slowly and in stages, especially from lying down to upright posture and dangle legs over bed for a few minutes before walking.
Note: Effectiveness can decrease with continued drug administration in some patients. Inform physician if this occurs.
Do NOT use OTC drugs while on a TCA without physician approval.
Do not drive or engage in other potentially hazardous activities until response to drug is known.
Avoid exposure to strong sunlight because of potential photosensitivity. Use sunscreen with at least SPF of 12–15 if allowed.

Common adverse effects in italic, life-threatening effects underlined; generic names in bold; classifications in SMALL CAPS; Canadian drug name; Prototype drug

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