clomipramine ANAFRANIL

Class: TCA/​Dihydrodibenzazepine
FDA Indications: OCD
Off-Label Use: Treatment Resistant Depression, Depression, Anxiety, Cataplexy, Insomnia, Neuropathic Pain
Prescribing
Forms: 25, 50, 75mg tablet
Dose Range: 75-300 mg/day
Starting: 25 mg qd qhs, ↑ over 2 weeks to 100mg qd; max dose generally 250mg qd
Stopping: ↓ 50% x3 days, then ↓ another 50% x3 days, then D/C entirely.
Monitoring: Suggested plasma level 300-1000 nmol/L

NAMI drug fact sheet

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; ↓  QT↑, arrhythmias, tachycardia, orthostatic hypotension; dose-related seizure risk (0.7% @ doses ≥300mg)
Side Effects: sedation/somnolence, weight gain, sexual dysfunction, anticholinergic side effects
Pharmacodynamics
1° MOA: Tricyclic antidepressant
Target: SERT, NET, H1, α1, M1, 5HT2A
Pharmacokinetics
t½: 32 (17-37)° TMAX: 4.7°
Substrate of: 2D6; 1A2, 3A4, 2C19, 2C9
Inhibits: 2D6, UGT; Induces:
Active Metabolites: N-desmethylclomipramine (t½ 54-77°); NET >> SERT inhibition
DDIs
  • - DO NOT CO-PRESCRIBE WITH MAOIs (need a 14-day washout period)
  • - caution combining with other CNS depressants & anticholingerics
  • - VPA may ↑ levels
  • - 2D6 inhibitors can ↑ serum levels; 2D6 inducers can ↓ serum levels
Misc
  • - considered to be the most powerful antidepressant ever made
  • - exhibits nonlinear pharmacokinetics
  • - OCD tx often requires doses ≥200mg
  • - unique among TCAs, clomipramine exhibits preferential selectivity for 5HT reuptake however its 2° metabolite, N-desmethylclomipramine, is an NE reuptake inhibitor
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 2.8%


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.

No dosage adjustment necessary.


All TCAs are hepatically metabolzed, highly protein bound and will accumulate, and associated with ↑ LFTs.

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Last updated April 20 2018 09:28:33. Disclaimer: This website does not provide medical advice, nor is it a substitute for clinical judgment.