imipramine TOFRANIL
Class: TCA/DihydrodibenzazepineFDA Indications: MDD
Off-Label Use: Enuresis, Anxiety, Chronic Pain, Sleep Terrors, Somnambulism, ADHD, Migraines, Neuropathic Pain, Eating Disorders, PTSD
Prescribing
Forms: 10, 25, 50mg tablet; 75, 100, 125, 150 mg Tofranil-PM™ capsuleDose Range: 75-300 mg/day
Starting: 25 mg qd qhs, ↑ by 25 mg q3-7 days, max dose 300 mg qd
Stopping: ↓ 50% x3 days, then ↓ another 50% x3 days, then D/C entirely.
Monitoring: Suggested plasma level 500-800 nmol/L (recommended for MDD)
Precautions
Contraindications: Concomitant use of MAOIs; patient s/p MI; coadministration of other QT-prolonging agents; h/o QT ↑ or arrhythmia; caution in patients with hypo-K+ or hypo-Mg2+Serious Side Effects: 5HT syndrome; ↓ seizure threshold; QT↑, arrhythmias, tachycardia, orthostatic hypotension
Possible Risk of TdP
Side Effects: anticholinergic side effects, weight gain, sexual dysfunction
Pharmacokinetics
t½: 32 (11-25)° TMAX: 1-2°Substrate of: 2D6, 2C19; 1A2, 3A4
Inhibits: ∅ ; Induces: ∅
Active Metabolites: desipramine
DDIs
- - DO NOT CO-PRESCRIBE WITH MAOIs (need a 14-day washout period)
- - caution combining with other CNS depressants & anticholingerics
Misc
- - the first antidepressant, first approved in 1959
- - its 2° metabolite, desipramine, is the most noradrenergic of all the TCAs
- - most preferred TCA for treating enuresis in children
Special Populations
Category C—A case-control study showed ∅ ↑ congenital malformations with 1st trimester use & a review (n=209) showed ∅ assoc with congenital malformations or developmental delay.
RID 0.15%
Avoid due to its anticholinergicity and high sedation, especially when combining with other CNS depressants and/or anticholingerics. Caution regarding orthostatic hypotension (fall risk!). Can impair cognition.
2019 BEE℞S Recommendation: Avoid. Highly anticholinergic, sedating, and cause orthostatic hypotension.
No dosage adjustment necessary.
All TCAs are hepatically metabolzed, highly protein bound and will accumulate, and associated with ↑ LFTs.
References
Applied Clinical Pharmacokinetics And Pharmacodynamics Of Psychopharmacological AgentsConcise Guide To Drug Interaction Principles For Medical Practice
Foye's Principles Of Medicinal Chemistry
Pharmacology For Women's Health
Drug Interactions In Psychiatry, 3rd Ed.
Antidepressant Use During Pregnancy
Thank you for using psychopharmacopeia.com!