Tofranil

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.

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: diarrhea, 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.