Dosing and uses of Tofranil, Tofranil-PM (imipramine)
Adult dosage forms and strengths
tablet
- 10mg
- 25mg
- 50mg
capsule
- 75mg
- 100mg
- 125mg
- 150mg
Depression
Outpatient: 75 PO qDay initially; may increase to 150 mg/day gradually; not to exceed 200 mg/day outpatient; may give in divided doses or single dose Hs
Inpatient: 100-150 mg/day PO; may increase gradually to 200 mg/day; if no response after 2 weeks, may increase further to 250-300 mg/day; not to exceed 300 mg/day; may give in divided doses or as a single dose at Hs
Maintenance dose: 50-100 mg PO qDay
Dosing considerations
- Patients may not see maximum antidepressant effect for >2 weeks
Pediatric dosage forms and strengths
tablet
- 10mg
- 25mg
- 50mg
capsule
- 75mg
- 100mg
- 125mg
- 150mg
Enuresis
10-25 mg PO qHS initially; may increase by 10-25 mg q1-2Week
6-12 years: Not to exceed 50 mg or 2.5 mg/kg/day Hs
12-14 years: Not to exceed 75 mg/day
Depression (Off-label)
1.5 mg/kg/day PO divided q8hr; may increase every 3-4 days by 1 mg/kg; not to exceed 5 mg/kg/day
Adolescents: 30-40 mg/day PO divided qDay or divided q8hr; not to exceed 100 mg/day
See Black Box Warning
Chronic Pain (Off-label)
0.2-0.4 mg/kg PO qHS; increase by 50% q2-3days to no more than 1-3 mg/kg PO qHs
Geriatric dosage forms and strengths
Depression
5-50 mg PO qHS; may increase q3days for inpatients and weekly for outpatient; not to exceed 100 mg/day
Dosing considerations
Avoid; strong anticholinergic and sedative effects; may cause orthostatic hypotension (Beers criteria)
Consider alternatives; if must use, initiate with lower initial dose
Tofranil, Tofranil-PM (imipramine) adverse (side) effects
Frequency not defined
Fatigue
Lethargy
Sedation
Weakness
Constipation
Dry mouth
Blurred vision
Agitation
Anxiety
Headache
Insomnia
Nausea
Vomiting
Sweating
ECG changes, orthostatic hypotension, tachycardia
Confusion, extrapyramidal symptoms (EPS), dizziness, paresthesia, tinnitus
Rash
Increased LFTs
Sexual dysfunction
Seizure
Agranulocytosis
Eosinophilia
Leukopenia
Thrombocytopenia
SIADH
Warnings
Black box warnings
In short-term studies, antidepressants increased the risk of suicidal thinking and behavior in children, adolescents, and young adults (<24 years) taking antidepressants for major depressive disorders and other psychiatric illnesses
This increase was not seen in patients aged over 24 years; a slight decrease in suicidal thinking was seen in adults aged over 65 years
In children and young adults, risks must be weighed against the benefits of taking antidepressants
Patients should be monitored closely for changes in behavior, clinical worsening, and suicidal tendencies; this should be done during the initial 1-2 months of therapy and dosage adjustments
The patient’s family should communicate any abrupt changes in behavior to the healthcare provider
Worsening behavior and suicidal tendencies that are not part of the presenting symptoms may require discontinuation of therapy
This drug is not approved for use in pediatric patients
Contraindications
Hypersensitivity
Acute recovery post-MI
Coadministration with serotonergic drugs
- Concomitant with or within 14 days of MAOIs (serotonin syndrome)
- Starting imipramine in a patient who is being treated with linezolid or IV methylene blue is contraindicated because of an increased risk of serotonin syndrome
- If linezolid or IV methylene blue must be administered, discontinue imipramine immediately and monitor for CNS toxicity; may resume imipramine 24 hr after last linezolid or methylene blue dose or after 2 weeks of monitoring, whichever comes first
Cautions
Risk of anticholinergic effects; use caution in BPH, urinary/GI retention, hyperthyroidism, oseizure disorder, brain tumor, respiratory impairment
Risk of mydriasis; may trigger angle closure attack in patients with angle closure glaucoma with anatomically narrow angles without a patent iridectomy
Clinical worsening and suicidal ideation may occur despite medication
Potentially life-threatening serotonin syndrome reported when coadministered with drugs that impair serotonin metabolism (in particular, MAOIs, including nonpsychiatric MAOIs, such as linezolid and IV methylene blue)
May cause bone marrow suppression (rare)
May cause orthostatic hypotension
May cause sedation and impair physical or mental abilities
Do not discontinue abruptly for prolonged high dosage
Pregnancy and lactation
Pregnancy category: d
Lactation: Distributed in breast milk; do not nurse (AAP states effect on nursing infants is unknown but may be of concern)
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of Tofranil, Tofranil-PM (imipramine)
Mechanism of action
Neurotransmitter (especially norepinephrine and serotonin) reuptake inhibitor; inhibits reuptake by neuronal membrane; may also down-regulate beta-adrenergic and serotonin receptors
Absorption
Bioavailability: Completely absorbed
Onset: After >2 weeks
Peak plasma time: 1-2 hr
Distribution
Vd: 18 L/kg
Protein bound: 90%
Metabolism
Hepatic CYP1A2, CYP2C19, CYP2D6
Metabolites: Desipramine
Elimination
Half-life: 6-18 hr
Excretion: Urine
