Dosing and uses of Anafranil (clomipramine)
Adult dosage forms and strengths
capsule
- 25mg
- 50mg
- 75mg
Obsessive-Compulsive Disorder
25 mg PO qDay initially
Gradually increase to 100 mg/day (divided with meals) over 2 weeks, THEn
May increase further to 250 mg/day maximum; may give as single daily dose qHS once tolerated
Other Indications & Uses
Off-label: premature ejaculation
Pediatric dosage forms and strengths
capsule
- 25mg
- 50mg
- 75mg
Obsessive-Compulsive Disorder
<10 years: Safety and efficacy not established
≥10 years: 25 mg PO qDay initially
Gradually increase to maximum 3 mg/kg/day or 100 mg/day, whichever is less
May further increase to maximum 3 mg/kg/day or 200 mg/day, whichever is less; may give as single dose qHS once tolerated
Geriatric dosage forms and strengths
Avoid; strong anticholinergic and sedative effects; may cause orthostatic hypotension (Beers criteria)
Consider alternatives; if must use, initiate with lower initial dose
25 mg PO qDay initially
Gradually increase to 100 mg/day (divided with meals) over 2 weeks, THEn
May increase further to 250 mg/day maximum; may give as single daily dose qHS once tolerated
Anafranil (clomipramine) adverse (side) effects
>10%
Xerostomia (84%)
Headache (50-55%)
Constipation (47%)
Ejaculation failure (42%)
Fatigue (35-40%)
Nausea (30-35%)
Impotence (20-25%)
Weight gain (18%)
1-10%
Weight loss (5%)
Hepatotoxicity (1-3%)
Frequency not defined
Common
- Dizziness, mainia, somnolence, tremor
- Dyspepsia
- Blurred vision
- Urinary retention
- Orgasm incapacity, libido change
Rare
- Myocardial infarction, orthostatic hypotension
- Depression worsening, suicidal thoughts suicide, seizure
- Hyperglycemia
- Agranulocytosis, leukopenia, pancytopenia, thrombocytopenia
- Body temperature above normal
Warnings
Black box warnings
In short-term studies, antidepressants increased the risk of suicidal thinking and behavior in children, adolescents, and young adults (<24 yr of age) taking antidepressants for major depressive disorders and other psychiatric illnesses
This increase was not seen in patients aged >24 years; a slight decrease in suicidal thinking was seen in adults >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 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
Severe cardiovascular disorder
Narrow angle glaucoma
Any drugs or conditions that prolong QT intervaL
Acute recovery post-MI
Coadministration with serotonergic drugs
- Concomitant with or within 14 d of MAOIs (serotonin syndrome)
- Starting clomipramine 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 clomipramine immediately and monitor for CNS toxicity; may resume clomipramine 24 hr after last linezolid or methylene blue dose or after 2 weeks of monitoring, whichever comes first
Cautions
BPH, urinary/GI retention, hyperthyroidism, seizure 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 suicide ideation may occur despite medication in adolescents and young adults (18-24 yr)
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)
Risk of anticholinergic side-effects
Pregnancy and lactation
Pregnancy category: C
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 Anafranil (clomipramine)
Mechanism of action
Parent drug may affect serotonin uptake; active metabolite may may affect norepinephrine uptake
Pharmacokinetics
Peak Plasma Time: 2-6 hr
Concentration: 56-154 ng/mL
Half-Life: 32 hr (parent drug), 69 hr (metabolite)
Excretion: Urine (60%); feces (32%)
Steady-state therpaeutic plasma concentration: 100-250 ng/mL (parent drug), 230-550 ng/mL (metabolite)
Bioavailability: 50%
Protein Bound: 97-98%
Vd: 17 L/kg
Metabolism: Hepatic CYP2D6
Metabolites: Desmethylclomipramine
Dialyzable: No
