Tofranil
[to-fra´nil]imipramine hydrochloride
imipramine pamoate
Pharmacologic class: Dibenzazepine derivative
Therapeutic class: Tricyclic antidepressant
Pregnancy risk category C
FDA Box 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.
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.