Pronunciation: kloe-MIH-pruh-meen HIGH-droe-KLOR-ide
Class: Tricyclic compound
- Capsules 25 mg
- Capsules 50 mg
- Capsules 75 mg
CO Clomipramine (Canada)
Inhibits reuptake of serotonin in CNS.
C max is approximately 92 ng/mL (single 50 mg dose). T max is approximately 4.7 h (single 50 mg dose). C max at steady state is approximately 218 ng/mL (multiple 150 mg doses). Concentrations and AUC are not dose-proportional. Time to steady state is 7 to 14 days.
Distributes into brain, breast milk, and CSF. Approximately 97% protein bound, principally to albumin.
Extensively biotransformed to desmethylclomipramine (active) and other metabolites.
The t ½ is 19 to 37 h. Metabolites are excreted in the urine and feces following biliary elimination.
Indications and Usage
Relief of obsessive-compulsive disorder.
Treatment of panic disorder; treatment of premenstrual symptoms.
Hypersensitivity to any tricyclic antidepressant. Not to be given in combination with or within 14 days of treatment with MAOIs. Not to be given during acute recovery phases of MI.
Dosage and AdministrationAdults Initial dose
PO 25 mg/day; gradually increase dose to 100 mg/day during first 2 wk. Dose then may be gradually increased to max of 250 mg/day.Children 10 yr of age and younger Initial dose
PO 25 mg/day; gradually increase dose to 3 mg/kg/day or 100 mg/day (whichever is less) during first 2 wk; then slowly increase dose to max 3 mg/kg/day or 200 mg/day (whichever is less).
- During titration phase, administer drug in divided doses daily with meals to lessen GI side effects.
- After titration, to minimize daytime sedation, give daily dose at bedtime with large glass of water.
Store at 68° to 77°F. Protect from moisture.
Effects may be increased.Charcoal
May increase effects of clomipramine.Cisapride
Cisapride is contraindicated in patients receiving tricyclic antidepressants.Clonidine
May result in hypertensive crisis.CNS depressants
Depressant effects may be additive.Drugs highly protein bound (eg, digoxin, warfarin)
Clomipramine may displace these agents from their plasma protein-binding sites, resulting in transient increases in plasma concentrations.Guanethidine
Antihypertensive effects may be decreased.Hepatic enzyme inducers (eg, barbiturates, hydantoins, rifamycins)
May decrease effects of clomipramine.Hepatic enzyme inhibitors (cimetidine, fluoxetine, haloperidol, oral contraceptives, phenothiazine antipsychotics)
May increase effects of clomipramine.MAOIs
Sweating, convulsions, and death may occur. Coadministration or use within 14 days before or after treatment with an MAOI is contraindicated.Phenobarbital
Levels may be elevated by clomipramine, increasing the pharmacologic and adverse effects.Quinolones (gatifloxacin, levofloxacin, moxifloxacin, sparfloxacin)
The risk of life-threatening cardiac arrhythmias may be increased.
Laboratory Test Interactions
None well documented.
Postural hypotension (6%); palpitation, tachycardia (4%); syncope (2%).
Dizziness, somnolence, tremor (54%); headache (52%); insomnia (25%); libido change (21%); nervousness (18%); myoclonus (13%); increased appetite (11%); anxiety, impaired memory, paresthesia (9%); twitching (7%); depression, impaired coordination (5%); hypertonia, sleep disorder (4%); abnormal dreaming, agitation, confusion, migraine, psychosomatic disorder, speech disorder, yawning (3%); aggressive reaction, asthenia, depersonalization, emotional lability, irritability, panic disorder, paresis (2%); abnormal thinking, vertigo (at least 1%); confusion, delusion, hallucinations, hypomania, mania, paranoia, psychotic episodes.
Increased sweating (29%); flushing, rash (8%); pruritus (6%); abnormal skin odor, acne, dermatitis, dry skin (2%); urticaria (1%).
Abnormal vision (18%); pharyngitis (14%); rhinitis (12%); tinnitus (6%); otitis media (4%); abnormal lacrimation (3%); anisocoria, blepharospasm, laryngitis, mydriasis, ocular allergy, vestibular disorder (2%); conjunctivitis (1%).
Dry mouth (84%); constipation (47%); nausea (33%), dyspepsia (22%); diarrhea (13%); anorexia (12%); abdominal pain (11%); vomiting (7%); flatulence (6%); tooth disorder (5%); dysphagia, eructation, GI disorder, halitosis, ulcerative stomatitis (2%); esophagitis (1%).
Ejaculation failure (42%); impotence (20%); micturition disorder (14%); dysmenorrhea (12%); urinary retention (7%); UTI (6%); micturition frequency (5%); menstrual disorder, nonpuerperal lactation (4%); breast enlargement, cystitis, dysuria, leucorrhea, vaginitis (2%); amenorrhea, breast pain (1%).
Agranulocytosis, anemia, leucopenia, pancytopenia, thrombocytopenia.
Elevated ALT (3%); elevated AST (1%).
Weight increase (18%); weight decrease (7%).
Bronchospasm (7%); coughing, sinusitis (6%); dyspnea, epistaxis (2%).
Fatigue (39%); allergy (7%); hot flashes (5%); chest pain, fever, pain (4%); chills, local edema (2%).
Antidepressants increase the risk of suicidal thinking and behavior in short-term studies in children and adolescents with major depressive disorders and other psychiatric disorders. Closely observe patients who are started on therapy for clinical worsening, suicidal, or unusual changes in behavior.
Monitor blood counts (CBC with differential), blood sugars (in patients with diabetes), ECG, and LFTs as needed.
Category C . Neonatal withdrawal symptoms have been reported.
Excreted in breast milk.
Not recommended for children younger than 10 yr of age.
Special Risk Patients
Use with caution in patients with angle-closure glaucoma or increased IOP, CV disorders, hepatic or renal function impairment, history of seizures, urethral or ureteral spasm, or urinary retention; hyperthyroid patients or those receiving thyroid medication; and schizophrenic or paranoid patients.
May precipitate hypomania or mania.
Neuroleptic malignant syndrome
Cases have been reported.
Signs and symptoms (eg, confusion, delusions, hallucinations, paranoia, psychotic episodes) have been reported.
Closely monitor patients at risk. Prescribe the smallest quantity consistent with good patient management to reduce the risk of overdose.
Symptoms including dizziness, headache, hyperthermia, irritability, malaise, nausea, sleep disturbances, and vomiting have been associated with sudden withdrawal of clomipramine.
Agitation, anuria, ataxia, athetoid and choreiform movement, cardiac dysrhythmias, CNS depression including coma, convulsions, cyanosis, delirium, drowsiness, ECG changes (particularly in QRS axis or width), hyperactivity reflexes, hyperpyrexia, muscle rigidity, mydriasis, oliguria, rare cardiac arrest, respiratory depression, restlessness, severe hypotension, severe perspiration, shock, signs of CHF, stupor, tachycardia, and vomiting.
- Advise patient, family, and caregiver to be alert to changes in behavior, worsening of depression, and suicidal thinking, all of which indicate a need for very close monitoring and possible change in medication.
- Instruct patient to keep weekly record of weight and to decrease caloric intake if necessary.
- Teach patient how to monitor BP and heart rate.
- Instruct patient on oral hygiene habits to prevent and treat dry mucous membranes.
- Advise patient to increase fluid intake.
- Instruct patient not to discontinue taking drug abruptly.
- Inform men of possible impotence or ejaculation failure.
- Caution patient to avoid sudden position changes to prevent orthostatic hypotension.
- Advise patient that drug may cause drowsiness and to use caution while driving or performing other tasks requiring mental alertness.
- Caution patient to avoid exposure to sunlight, use sunscreen, and wear protective clothing to avoid photosensitivity reaction.
- Advise patient to avoid intake of alcohol, sedative/hypnotics, or other CNS depressants.
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