General

Pronunciation
kloe-MIP-ra-meen

Trade Name(s)

• Anafranil

Pregnancy Category
Category C

Ther. class.
antiobsessive agents

Pharm. class.
tricyclic antidepressants

Indications

Obsessive-Compulsive Disorder (OCD)

Unlabelled Use(s):
Depression, neuropathic pain/chronic pain.

Action

Potentiates the effect of serotonin (antiobsessional effect) and norepinephrine in the CNS. Has moderate anticholinergic effects

Therapeutic Effect(s):
Diminished obsessive-compulsive behavior

Pharmacokinetics

Absorption: Well absorbed from the GI tract

Distribution: Widely distributed, enters breast milk

Protein Binding: >=90%

Metabolism and Excretion: Extensively metabolized by the liver. Some conversion to a pharmacologically active metabolite (desmethylclomipramine). Undergoes enterohepatic recirculation and secretion into gastric juices

Half-life: 21–31 hr

TIME/ACTION PROFILE

ROUTE	ONSET	PEAK	DURATION
PO	1–6 wk	unknown	unknown

Contraindication/Precautions

Contraindicated in:

• Hypersensitivity

• Angle-closure glaucoma

• Recent myocardial infarction

• History of QTc prolongation

• Cardiac arrythmias

• Heart failure

• Concurrent MAO inhibitor or clonidine use (avoid if possible)

• OB: Potential for fetal harm or neonatal withdrawal syndrome

• Lactation: Discontinue drug or bottle feed

Use Cautiously in:

• History of seizures (threshold may be lowered)

• Patients with pre-existing cardiovascular disease

• Older men with prostatic hyperplasia (may be more susceptible to urinary retention)

• Hyperthyroidism (increased 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: Safety not established in children <10 yr

• Geri: risk of arrhythmias

Adverse Reactions/Side Effects

CNS: SEIZURES, lethargy, sedation, weakness, aggressive behavior.

EENT: blurred vision, dry eyes, dry mouth, vestibular disorder.

CV: ARRHYTHMIAS, ECG changes, orthostatic hypotension.

GI: constipation, nausea, vomiting, weight gain, eructation.

GU: male sexual dysfunction, urinary retention.

Derm: dry skin, photosensitivity.

Endo: gynecomastia.

Hemat: anemia.

MS: muscle weakness.

Neuro: extrapyramidal reactions.

Misc: hyperthermia.

*CAPITALS indicates life-threatening.
*italic indicates most frequent.

Interactions

Drug-Drug

• May cause hypotension and tachycardia when used with MAO inhibitors (concurrent use not recommended)

• Wait 2 wks before initiating clomipramine after MAO Inhibitors are stopped

• Wait 2 wks before initiating MAO Inhibitors after clomipramine is stopped

• May prevent the therapeutic response to antihypertensives

• Use with clonidine may result in hypertensive crisis (avoid concurrent use)

• CNS depression with other CNS depressants including alcohol, 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 weeks after stopping SSRIs to start clomipiramine; up to 5 weeks for fluoxetine), phenothiazines, cimetidine, or oral contraceptives

• Nicotine may metabolism and effectiveness

• Transient delirium may occur with disulfiram

Drug-Natural Products

• Increased risk of serotonergic side effects including serotonin syndrome with St. John's wort and SAMe

• Kava, valerian, or chamomile can increase CNS depression

Drug-Food
Grapefruit juice serum levels and effect

Route/Dosage

• PO (Adults):
Antiobsessive—25 mg/day, increased over 2-wk period to 100 mg/day in divided doses. May be further increased over several weeks up to 250–300 mg/day in divided doses. Once stabilizing dose is reached, entire daily dose may be given at bedtime.
Antidepressant—25 mg 3 times daily, may be increased as needed (unlabeled).

• PO (Geriatric Patients): 20–30 mg/day initially, may be increased as needed.

• PO (Children >10–17 yr): 25 mg/day initially, increased over 2-wk period to 3 mg/kg/day or 100 mg/day (whichever is smaller) in divided doses. May be further increased 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

• Capsules: 10 mg, 25 mg, 50 mg, 75 mg

Assessment

• Monitor mental status (orientation, mood, behanior) frequently. Assess patient for frequency of OCD. Note degree to which these thoughts and behaviors interfere with daily functioning

• Monitor blood pressure and pulse before and during initial therapy. Notify physician or other health care professional of decreases in blood pressure (10–20 mmHg) or sudden increase in pulse rate. Patients taking high doses or with a history of cardiovascular disease should have ECG monitored before and periodically during therapy

• Assess weight and BMI initially and throughout treatment. Assess FBS 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

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

Potential Nursing Diagnoses

• Ineffective coping (obsessive-compulsive behaviors), related to repressed anxiety (Indications)

• Risk for injury (Side Effects)

• Chronic pain (Indications)

Implementation

• Do not confuse clomipramine with clomiphene or desipramine

• 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

• 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 during course of therapy and for 3–7 days after cessation of therapy

• 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, dosage reduction or discontinuation may be necessary. Consult health care professional if dry mouth persists for more than 2 wk

• Advise patient to inform health care professional if sexual dysfunction occurs. Inform male patients that sexual dysfunction is common with this medication

• 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

• Emphasize the importance of follow-up exams to monitor effectiveness and side effects and to improve coping skills

• Inform patients taking high doses (250–300 mg/day) that risk of seizures is increased

• Refer patient to local OCD group

Evaluation/Desired Outcomes

Diminished obsessive compulsive behavior

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