clomipramine

Absorption: Well absorbed from the GI tract.

Distribution: Widely distributed to tissues.

Protein Binding: ≥90%.

Metabolism/Excretion: Mostly metabolized by the liver by the CYP2D6 isoenzyme; the CYP2D6 enzyme system exhibits genetic polymorphism; ∼7% of population may be poor metabolizers (PMs) and may have significantly ↑ clomipramine concentrations and an ↑ risk of adverse effects; .

Half-Life: 21–31 hr.

Time/Action Profile ⬆ ⬇

ROUTE	ONSET	PEAK	DURATION
PO	1–6 wk	unknown	unknown

Contraind./Precautions ⬆ ⬇

Contraindicated in:

Hypersensitivity;
Angle-closure glaucoma;
Recent MI;
History of QTc interval prolongation;
Cardiac arrhythmias;
HF;
Concurrent use of MAO inhibitors or MAO-like drugs (linezolid or methylene blue) .
OB: Pregnancy;
Lactation: Lactation.

Use Cautiously in:

History of seizures (may lower seizure threshold);
Pre-existing cardiovascular disease;
Older men with prostatic hyperplasia (may be more susceptible to urinary retention);
Volume depletion or recent use of diuretics (↑ risk of hyponatremia);
Hyperthyroidism (↑ risk of arrhythmias);
May ↑ risk of suicide attempt/ideation especially during dose early treatment or dose adjustment; risk may be greater in children or adolescents;
Pedi: Children 10 yr (safety and effectiveness not established);
Geri: Appears on Beers list. risk of adverse reactions in older adults, including falls secondary to sedative and anticholinergic effects and orthostatic hypotension. Avoid use in older adults.

Adv. Reactions/Side Effects ⬆ ⬇

CV: ECG changes, ARRHYTHMIAS, orthostatic hypotension

Derm: DRUG REACTION WITH EOSINOPHILIA AND SYSTEMATIC SYMPTOMS (DRESS), dry skin, photosensitivity

EENT: blurred vision, dry eyes, vestibular disorder

Endo: gynecomastia, syndrome of inappropriate antidiuretic syndrome (SIADH)

F and E: hyponatremia

GI: vomiting, constipation, dry mouth, nausea, eructation

GU: male sexual dysfunction, urinary retention

Hemat: anemia

Metab: weight gain

MS: muscle weakness

Neuro: sedation, weakness, aggressive behavior, extrapyramidal reactions, SEIZURES, SUICIDAL THOUGHTS

Misc: hyperthermia

Interactions ⬆ ⬇

Drug-drug:

Concurrent use with MAO inhibitors may result in serious potentially fatal reactions (MAO inhibitors should be stopped at least 14 days before clomipramine therapy. Clomipramine should be stopped at least 14 days before MAO inhibitor therapy).
Concurrent use with MAO-inhibitor like drugs, such as linezolid or methylene blue may ↑ risk of serotonin syndrome; concurrent use contraindicated; do not start therapy in patients receiving linezolid or methylene blue; if linezolid or methylene blue need to be started in a patient receiving clomipramine, immediately discontinue clomipramine and monitor for signs/symptoms of serotonin syndrome for 2 wk or until 24 hr after last dose of linezolid or methylene blue, whichever comes first (may resume clomipramine therapy 24 hr after last dose of linezolid or methylene blue)
May prevent the therapeutic response to antihypertensives.
Hypertensive crisis may occur with clonidine.
↑CNS depression with other CNS depressants includingalcohol, antihistamines, opioids, and sedative/hypnotics.
Adrenergic and anticholinergic side effects may be ↑ with other agents having adrenergic/anticholinergic properties.
Effects and toxicity may be ↑ by concurrent use with SSRI antidepressants (wait several wk after stopping SSRIs to start clomipramine; up to 5 wk for fluoxetine), phenothiazines, cimetidine, or oral contraceptives.
Drugs that affect serotonergic neurotransmitter systems, including SSRIs, SNRIs, fentanyl, buspirone, tramadol and triptans↑ risk of serotonin syndrome.
Nicotine may ↑ metabolism and ↓ effectiveness.
Transient delirium may occur with disulfiram.

Drug-Natural Products:

Use with St. John's wort↑ of serotonin syndrome.
Kava, valerian, or chamomile can ↑ CNS depression.

Grapefruit juice↑ levels and risk of toxicity.

Route/Dosage ⬆ ⬇

PO (Adults ): 25 mg once daily, ↑ over 2-wk period to 100 mg/day in divided doses. May be further ↑ over several wk up to 250–300 mg/day in divided doses. Once stabilizing dose is reached, entire daily dose may be given at bedtime.
PO (Children >10 yr): 25 mg once daily initially, ↑ over 2-wk period to 3 mg/kg/day or 100 mg/day (whichever is smaller) in divided doses. May further ↑ to 3 mg/kg/day or 200 mg/day (whichever is smaller) in divided doses. Once stabilizing dose is reached, entire daily dose may be given at bedtime.

Availability ⬆ ⬇

(Generic available)

Capsules: 25 mg; 50 mg; 75 mg
Tablets: 10 mg; 25 mg; 50 mg

Assessment ⬆ ⬇

Monitor mental status (orientation, mood, behavior) frequently. Assess patient for frequency of OCD behaviors. Note degree to which these thoughts and behaviors interfere with daily functioning.
Monitor BP and pulse before and during initial therapy. Notify health care professional of decreases in BP (10–20 mm Hg) or sudden increase in pulse rate. Monitor ECG before and periodically during therapy in patients taking high doses or with a history of cardiovascular disease.
Assess weight and BMI initially and during treatment. Assess fasting blood sugar and cholesterol levels in obese individuals. Refer as appropriate for nutritional/weight management and medical management.
Observe for onset of extrapyramidal parkinsonian side effects (difficulty speaking or swallowing, loss of balance control, pill rolling with hands, mask-like face, shuffling gait, rigidity, tremors). Notify physician or other health care professional if these symptoms occur; reduction in dose or discontinuation of medication may be necessary. Trihexyphenidyl or diphenhydramine may be used to control these symptoms.
Assess for suicidal tendencies, especially during early therapy and dose changes. Restrict amount of drug available to patient. Risk may be increased in children, adolescents, and adults ≤24 yr. After starting therapy, children, adolescents, and young adults should be seen by health care professional at least weekly for 4 wk, every 3 wk for next 4 wk, and on advice of health care professional thereafter.
Assess for serotonin syndrome (mental changes [agitation, hallucinations, coma], autonomic instability [tachycardia, labile BP, hyperthermia], neuromuscular aberrations [hyperreflexia, incoordination], and/or GI symptoms [nausea, vomiting, diarrhea]), especially in patients taking other serotonergic drugs (SSRIs, SNRIs, triptans).
Monitor for signs and symptoms of DRESS (fever, rash, lymphadenopathy, and/or facial swelling, associated with involvement of other organ systems (hepatitis, nephritis, hematologic abnormalities, myocarditis, myositis) during therapy. May resemble an acute viral infection. Eosinophilia is often present. Discontinue therapy if signs occur.

Lab Test Considerations:

Serum glucose may be ↑ or ↓.
- Monitor CBC and differential during chronic therapy. May rarely cause bone marrow suppression.
- In chronic therapy, periodically monitor hepatic and renal function.

Implementation ⬆ ⬇

Do not confuse clomipramine with clomiphene.
PO: Administer medication with or immediately after a meal to minimize gastric irritation. After titration of dose, total daily dose may be given at bedtime.

Patient/Family Teaching ⬆ ⬇

Instruct patient to take medication exactly as directed. Abrupt discontinuation may cause nausea, headache, and malaise.
Advise patient to avoid grapefruit juice and grapefruit products during therapy.
May cause drowsiness and blurred vision. Caution patient to avoid driving and other activities requiring alertness until response to drug is known.
Orthostatic hypotension, sedation, and confusion are common during early therapy, especially in geriatric patients. Protect patient from falls and advise patient to change positions slowly.
Advise patient to avoid alcohol or other CNS depressant drugs, including opioids, during therapy and for 3–7 days after cessation of therapy.
Advise patient, family, and caregivers to look for suicidality, especially during early therapy or dose changes. Notify health care professional immediately if thoughts about suicide or dying, attempts to commit suicide, new or worse depression or anxiety, agitation or restlessness, panic attacks, insomnia, new or worse irritability, aggressiveness, acting on dangerous impulses, mania, or other changes in mood or behavior or if symptoms of serotonin syndrome or DRESS occur.
Instruct patient to notify health care professional of all Rx or OTC medications, vitamins, or herbal products being taken and to consult health care professional before taking any other Rx, OTC, or herbal products especially St. Johns Wort.
Inform patients taking high doses (250–300 mg/day) that risk of seizures is increased.
Instruct patient to notify health care professional if dry mouth or constipation persists or if urinary retention, uncontrolled movements, or rigidity occurs. Sugarless candy or gum may diminish dry mouth, and an increase in fluid intake or bulk may prevent constipation. If these symptoms persist, dose reduction or discontinuation may be necessary. Consult health care professional if dry mouth persists for more than 2 wk.
Caution patient to use sunscreen and protective clothing to prevent photosensitivity reactions.
Inform patient of need to monitor dietary intake because possible increase in appetite may lead to undesired weight gain.
Advise patient to notify health care professional of medication regimen before treatment or surgery.
Advise patient to inform health care professional if sexual dysfunction occurs. Inform male patients that sexual dysfunction is common with this medication.
Rep: Instruct female patients of reproductive potential to inform health care professional if pregnancy is planned or suspected, and to avoid breastfeeding during therapy.
Emphasize the importance of follow-up exams to monitor effectiveness and side effects and to improve coping skills.

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Pronunciation ⬇

Classifications ⬆ ⬇

Indications ⬆ ⬇

Action ⬆ ⬇

Pharmacokinetics ⬆ ⬇