Tofranil

To·fra·nil (t-frnl)

A trademark for the drug imipramine pamoate.

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Tofranil,

trademark for a tricyclic antidepressant (imipramine hydrochloride).

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Tofranil [to-fra´nil]

trademark for preparations of imipramine, a tricyclic antidepressant.

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imipramine hydrochloride

Apo-Imipramine (CA), Impril (CA), Novopramine (CA), Tofranil

Pharmacologic class: Dibenzazepine derivative

Therapeutic class: Tricyclic antidepressant

Pregnancy risk category C

FDA Boxed Warning

• Drug may increase risk of suicidal thinking and behavior in children and adolescents with major depressive disorder and other psychiatric disorders, especially during first few months of therapy. Risk must be balanced with clinical need, as depression itself increases suicide risk. With patient of any age, observe closely for clinical worsening, suicidality, and unusual behavior changes when therapy begins. Advise family and caregivers to observe patient closely and communicate with prescriber as needed.
• Drug isn't approved for use in pediatric patients.

Action

Unknown. May block reuptake of norepinephrine and serotonin at neuronal membrane, potentiating their effects.

Availability

Capsules: 75 mg, 100 mg, 125 mg, 150 mg (pamoate)

Tablets: 10 mg, 25 mg, 50 mg (hydrochloride)

⊘Indications and dosages

➣ Endogenous depression

Adults: 75 to 100 mg P.O. daily in divided doses. Don't exceed 200 mg/day for outpatients or 300 mg/day for inpatients. Elderly patients, adolescents: 30 to 40 mg P.O. daily in divided doses, up to 100 mg/day

➣ Functional enuresis

Children: 25 mg P.O. daily 1 hour before bedtime. If necessary, increase by 25 mg/day at weekly intervals, up to 75 mg P.O. daily in children ages 12 and older or up to 50 mg P.O. daily in children younger than age 12.

➣ Attention deficit hyperactivity disorder

Children ages 6 and older: 2 to 5 mg/kg P.O. daily in two or three divided doses

Off-label uses

• Diabetic neuropathy

Contraindications

• Hypersensitivity to drug or bisulfites
• Untreated angle-closure glaucoma
• MAO inhibitor use within past 14 days

Precautions

Use cautiously in:
• cardiovascular disease, prostatic enlargement, seizures, urinary retention
• elderly patients
• pregnant or breastfeeding patients.

Administration

☞ Don't give concurrently with MAO inhibitors. Interaction may lead to hypotension, tachycardia, and potentially fatal reactions.
• Give with food or milk if GI upset occurs.

Route	Onset	Peak	Duration
P.O.	Unknown	30 min-2 hr	2-6 wk

Adverse reactions

CNS: fatigue, sedation, agitation, confusion, hallucinations, drowsiness, dizziness, syncope, extrapyramidal effects, poor concentration, cerebrovascular accident, seizures, suicidal behavior or ideation (especially in child or adolescent)

CV: hypotension, ECG changes, hypertension, vasculitis, palpitations, tachycardia, arrhythmias , myocardial infarction, heart block

EENT: blurred vision, increased intraocular pressure (IOP), lacrimation, tinnitus, nasal congestion

GI: nausea, constipation, dry mouth, paralytic ileus

GU: urinary retention, urinary tract dilation, gynecomastia, menstrual irregularities, galactorrhea, testicular swelling, libido changes, erectile dysfunction

Hematologic: eosinophilia, purpura, bone marrow suppression, agranulocytosis, thrombocytopenia, leukopenia

Hepatic: hepatitis

Metabolic: hyperthermia, hyperglycemia, hypoglycemia

Skin: flushing, diaphoresis, photosensitivity, rash, urticaria, pruritus, petechiae, alopecia

Other: increased appetite, weight gain or loss, edema, drug fever, chills, hypersensitivity reactions

Interactions

Drug-drug. Adrenergics: increased hypertensive effect

Carbamazepine, class IC antiarrhythmics, other antidepressants, phenothiazines: additive effects of imipramine

CNS depressants: additive CNS depression

Clonidine: decreased clonidine effects

CYP450-2D6 inhibitors (such as amiodarone, cimetidine, quinidine, ritonavir): increased imipramine effects

Guanethidine: prevention of therapeutic response to imipramine

Levodopa: delayed or decreased levodopa absorption, hypertension

MAO inhibitors: hypotension, tachycardia, potentially fatal reactions

Selective serotonin reuptake inhibitors: increased imipramine blood level

Sparfloxacin: increased risk of cardiovascular reactions

Drug-diagnostic tests. Alkaline phosphatase, bilirubin: elevated levels

Glucose: increased or decreased level

Liver function tests: altered values

Drug-herbs. Angel's trumpet, jimsonweed, scopolia: increased anticholinergic effects

Chamomile, hops, kava, skullcap, valerian: increased CNS depression

Evening primrose oil: additive or synergistic effects

S-adenosylmethionine (SAM-e), St. John's wort: serotonin syndrome

Drug-behaviors. Alcohol use: increased CNS depression

Smoking: increased metabolism and altered effects of imipramine

Sun exposure: increased risk of photosensitivity

Patient monitoring

☞ Closely monitor patient's mood and assess his risk for self-harm. Limit drug access if he may be suicidal.
• Assess for urinary retention and increased IOP in patients with history of urinary retention or angle-closure glaucoma.
☞ Monitor blood pressure before and during therapy and before dosage increases.
• Watch for arrhythmias in patients with history of cardiac disease.
• During withdrawal, monitor for adverse effects, such as headache, malaise, nausea, vomiting, and sleep disturbances.
• Assess for signs and symptoms of infection. Monitor CBC with white cell differential.

Patient teaching

☞ Teach patient or caregiver to recognize and immediately report signs of suicidal intent or expressions of suicidal ideation (especially in child or adolescent).
• Instruct patient to eat small, frequent meals to minimize GI upset.
• Inform patient that drug may cause changes in sexual function, such as erectile dysfunction and decreased libido.
☞ Tell patient to immediately report seizure, chest pain, abdominal pain or bloating, easy bruising or bleeding, unusual tiredness, or yellowing of skin or eyes.
• Advise patient to report fever, chills, sore throat, dry mouth, excessive sedation, difficulty urinating, or palpitations.
• Caution patient to avoid driving and other hazardous activities until he knows how drug affects concentration and alertness.
• As appropriate, review all other significant and life-threatening adverse reactions and interactions, especially those related to the drugs, tests, herbs, and behaviors mentioned above.

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Tofranil®

See Imipramine and desimipramine.