CLOMIPRAMINE HYDROCHLORIDE

CLOMIPRAMINE HYDROCHLORIDE
(clo-mi'pra-meen)
Anafranil
Classifications: psychotherapeutic; tricyclic antidepressant;
Therapeutic: antipsychotic
; tricyclic antidepressant
Prototype: Imipramine
Pregnancy Category: C

Availability

25 mg, 50 mg, 75 mg capsules

Action

Inhibits the reuptake of norepinephrine and serotonin at the presynaptic neuron. Of the tricyclic antidepressants (TCAs), it is the most selective and potent inhibitor of serotonin (5-HT) reuptake.

Therapeutic Effect

The basis of its antidepressant effects is thought to be due to the elevated serum levels of norepinephrine and serotonin.

Uses

Obsessive-compulsive disorder (OCD).

Unlabeled Uses

Panic disorder, anxiety, agoraphobia.

Contraindications

Hypersensitivity to other tricyclic compounds; acute recovery period after MI, QT elongation, cardiac arrhythmias (AV block, bundle-branch block); suicidal ideation; children <10 y, pregnancy (category C).

Cautious Use

History of convulsive disorders, prostatic hypertrophy, urinary retention, cardiovascular, hepatic, GI, or blood disorders; history of seizure disorder; respiratory depression; older adults; diabetes mellitus; GERD; Parkinson's disease; closed angle glaucoma; asthma; bipolar disorder; history of suicidal ideation; lactation.

Route & Dosage

Obsessive-Compulsive Disorder
Adult: PO 75–300 mg/d in divided doses
Child (10–18 y): PO 100–200 mg/d in divided doses, start at 50 mg/d

Depression
Adult: PO 50–150 mg/d in single or divided doses

Administration

Oral
  • Give in divided doses with meals to reduce GI adverse effects.
  • Following titration to the full dose, drug may be given as a single dose at bedtime to reduce daytime sedation.
  • Store at 15°–30° C (59°–86° F).

Adverse Effects (≥1%)

Body as a Whole: Diaphoresis. CV: Hypotension, tachycardia. GI: Constipation, dry mouth. Endocrine: Galactorrhea, hyperprolactinemia, amenorrhea, weight gain. Hematologic: Leukopenia, agranulocytosis, thrombocytopenia, anemia. CNS: Mania, tremor, dizziness, hyperthermia, neuroleptic malignant syndrome, seizures (especially with abrupt withdrawal). Urogenital: Delayed ejaculation, anorgasmia.

Diagnostic Test Interference

Clomipramine appears to elevate serum prolactin levels. Serum AST and ALT are elevated. Serum levels of triiodothyronine (T3) and free triiodothyronine (FT3) have been significantly reduced from baseline. Thyroxine-binding globulin (TBG) levels were increased from baseline, whereas thyroxine (T4), free thyroxine (FT4), and reverse T3 were unchanged.

Interactions

Drug: mao inhibitors may precipitate hyperpyrexic crisis, tachycardia, or seizures; antihypertensive agents potentiate orthostatic hypotension; cns depressants, alcohol add to CNS depression; norepinephrine and other sympathomimetics may increase cardiac toxicity; cimetidine decreases hepatic metabolism, thus increasing imipramine levels; methylphenidate inhibits metabolism of imipramine and thus may increase its toxicity. Herbal: Ginkgo may decrease seizure threshold; St. John's wort may cause serotonin syndrome.

Pharmacokinetics

Absorption: Rapidly absorbed from GI tract; 20–78% reaches systemic circulation. Onset: Depression: approx 2 wk; OCD: approx 4–10 wk. Peak: 2–6 h. Distribution: Widely distributed including the CSF; crosses placenta. Metabolism: Extensive first-pass metabolism in the liver; active metabolite is desmethylclomipramine. Elimination: 50–60% in urine, 24–32% in feces. Half-Life: 20–30 h.

Nursing Implications

Assessment & Drug Effects

  • Monitor for seizures, especially in those with predisposing factors such as alcoholism, brain injury, or concurrent therapy with other drugs that lower seizure threshold.
  • Lab tests: Periodic CBC with differential, platelet count, and Hct and Hgb. Monitor liver functions, especially with long-term therapy.
  • Monitor for and report signs of neuroleptic malignant syndrome (see Appendix F).
  • Monitor for sedation and vertigo, especially at the beginning of therapy and following dosage increases. Supervision of ambulation may be indicated.
  • Notify physician of fever and complaints of sore throat since these may indicated need to rule out adverse hematologic changes.

Patient & Family Education

  • Do not take nonprescribed drugs or discontinue therapy without consent of physician. Abrupt discontinuation may cause nausea, headache, malaise, or seizures.
  • Men should understand that the drug may cause impotence or ejaculation failure. Advise them to report this problem to physician.
  • Report promptly a sore throat accompanied by fever.
  • Use caution with ambulation until response to drug is known.
  • Moderate alcohol intake since it may potentiate adverse drug effects.

Common adverse effects in italic, life-threatening effects underlined; generic names in bold; classifications in SMALL CAPS; Canadian drug name; Prototype drug

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