clomipramine (Anafranil)
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Introduction
Tradename: Anafranil.
Indications
Contraindications
- recent myocardial infarction
- do not use with 14 days of MAO inhibitor
Dosage
Start 25 mg PO QD, max 250 mg/day
May be given as single dose QHS.
Tabs: 25, 50, 75 mg.
Pharmacokinetics
- well absorbed after oral administration
- extensive 1st pass metabolism
- active metabolite desmethyl-clomipramine
- 8-OH-clomipramine & 8-OH-desmethyl-clomipramine may have biological activity
- metabolism is highly variable
- 1/2life 20-30 hours[2]
- effects usually seen in 4-8 weeks of therapy, but may occur within 2-3 weeks
elimination via liver
1/2life = 15-62 hours
protein binding = 90-98 %
elimination by hemodialysis = -
elimination by hemoperfusion = -
elimination by peritoneal dialysis = -
Adverse effects
- common (> 10%)
- anticholinergic side effects
- headache
- increased appetite & weight gain
- nausea
- weakness
- unpleasant taste
- less common (1-10%)
- uncommon (< 1%)
- agranulocytosis, leukopenia, eosinophilia, alopecia, anxiety, breast enlargement, galactorrhea, cholestatic jaundice, seizures, SIADH, tinnitus, testicular swelling, gingivitis, decreased lower esophageal sphincter tone, GERD, increased liver function tests (LFTs) allergic reactions, photosensitivity
- other[2]
- overdose results in prolongation of the QT interval
- drug adverse effects of tricyclic antidepressants
- drug adverse effects of antidepressants
- drug adverse effects of psychotropic agents
Drug interactions
- serotonin syndrome may occur with concurrent administration of other serotonergic agents
- MAO inhibitors
- potential additive effects with alcohol, CNS depressants, anticholinergic agents & sympathomimetics
- clomipramine blocks the uptake of guanethidine & clonidine
- neuroleptics may inhibit metabolism & lead to higher concentrations of active metabolite desmethyl- clomipramine
- any drug which inhibits cyt P450 1A2, cyt P450 2D6 or cyt P450 3A4 can increase clomipramine levels
- any drug which induces cyt P450 1A2, cyt P450 2D6 or cyt P450 3A4 can diminish clomipramine levels
- drug interaction(s) of tricyclic antidepressants with physostigmine
- drug interaction(s) of antidepressant in combination with GLP1-agonist
- drug interaction(s) of benzodiazepines with antidepressants
- drug interaction(s) of antidepressants with benzodiazepines
- drug interaction(s) of NSAIDs with antidepressants
- drug interaction(s) of antidepressant with opiates
Laboratory
- specimen: serum, plasma (EDTA), whole blood, urine
- methods:
- interferences:
- desmethyl & 2-OH metabolites may interfere with parent compound in HPLC assays
Mechanism of action
- inhibits re-uptake of serotonin & norepinephrine
- antagonizes dopaminergic neurotransmission
- inhibits cyt P450 2D6[5]
More general terms
Additional terms
- cytochrome p450 1A2 (cytochrome P3-450, phenacetin deethylase, cytochrome p450-4, CYP1A2)
- cytochrome P450 2C19 (cytochrome P450 2C17, cytochrome P450 11A, mephenytoin 4-hydroxylase, cytochrome P450 254C, CYP2C19)
- cytochrome P450 3A4 (cytochrome P450 C3, nifedipine oxidase, P450-PCN1, NF-25, CYP3A4)
References
- ↑ The Pharmacological Basis of Therapeutics, 9th ed. Gilman et al, eds. Permagon Press/McGraw Hill, 1996
- ↑ 2.0 2.1 2.2 Drug Information & Medication Formulary, Veterans Affairs, Central California Health Care System, 1st ed., Ravnan et al eds, 1998 - not on National VA formulary
- ↑ Kaiser Permanente Northern California Regional Drug Formulary, 1998
- ↑ Clinical Guide to Laboratory Tests, 3rd ed. Teitz ed., W.B. Saunders, 1995
- ↑ 5.0 5.1 5.2 Prescriber's Letter 13(3): 2006 Cytochrome P450 drug interactions Detail-Document#: http://prescribersletter.com/(5bhgn1a4ni4cyp2tvybwfh55)/pl/ArticleDD.aspx?li=1&st=1&cs=&s=PRL&pt=3&fpt=25&dd=220233&pb=PRL (subscription needed) http://www.prescribersletter.com
- ↑ 6.0 6.1 Deprecated Reference