Chlordiazepoxide / Amitriptyline

Pronunciation: KLOR-dye-AZ-e-POX-ide/A-mi-TRIP-ti-leen
Class: Psychotherapeutic combination

Trade Names

Limbitrol
- Tablets 5 mg chlordiazepoxide and 12.5 mg amitriptyline

Limbitrol DS 10-25
- Tablets 10 mg chlordiazepoxide and 25 mg amitriptyline

Pharmacology

Amitriptyline blocks reuptake of serotonin and norepinephrine in CNS. Chlordiazepoxide potentiates effects of GABA in CNS.

Slideshow: Depression, the Risk of Suicide, and Treatment Options

Indications and Usage

Treatment of moderate to severe depression associated with moderate to severe anxiety.

Contraindications

Hypersensitivity to chlordiazepoxide or other benzodiazepines; hypersensitivity to amitriptyline or other tricyclic antidepressants; concomitant use of or use within 14 days of discontinuing an MAOI; acute recovery phase of MI.

Dosage and Administration

PO 1 tablet (chlordiazepoxide 10 mg with amitriptyline 25 mg) 3 or 4 times daily. May increase to 6 tablets daily if needed; some patients may respond to 1 tablet twice daily.

General Advice

  • If patient has been taking an MAOI, wait 2 wk before beginning chlordiazepoxide/amitriptyline therapy. Cautiously begin treatment with reduced dosage.
  • Administer with food or water to reduce gastric irritation.

Storage/Stability

Store at 59° to 86°F, in a dry place.

Drug Interactions

Alcohol, CNS depressants

Depressant effects may be additive.

Azole antifungal agents (eg, ketoconazole), cimetidine, fenfluramine, haloperidol, phenothiazine antipsychotic compounds, oral contraceptives, terbinafine, valproic acid

May cause increased amitriptyline blood levels.

Azole antifungal agents (eg, ketoconazole), cimetidine, disulfiram, fluoxetine, isoniazid, metoprolol, oral contraceptives, propoxyphene, propranolol, valproic acid

May increase chlordiazepoxide effects.

Carbamazepine

Plasma concentrations may be elevated by amitriptyline, increasing the risk of toxicity.

Clonidine

May result in hypertensive crisis.

CYP2D6 inhibitors (eg, cimetidine, flecainide, procainamide, quinidine, SSRIs [eg, fluoxetine, paroxetine, sertraline])

Amitriptyline plasma levels may be elevated, increasing the risk of toxicity. Allow at least 5 wk after discontinuation of fluoxetine before starting amitriptyline.

Digoxin

May increase digoxin serum levels.

Guanethidine

May diminish antihypertensive effects.

Hydantoins (eg, phenytoin)

Plasma levels may be elevated by chlordiazepoxide, increasing the risk of toxicity.

Levodopa

Efficacy of levodopa may be reduced.

MAOIs

May result in hypertensive crises, seizures, and death.

Oral anticoagulants

May result in increased anticoagulant effect.

Oral contraceptives

May prolong chlordiazepoxide t ½ .

St. John's wort

Amitriptyline concentrations may be reduced, decreasing the efficacy.

Sympathomimetics (eg, epinephrine)

The effects of epinephrine may be increased.

Laboratory Test Interactions

None well documented.

Adverse Reactions

Cardiovascular

Arrhythmias, heart block, hypertension, hypotension, MI, palpitations, stroke, tachycardia.

CNS

Apprehension, ataxia, delusions, EEG pattern changes, euphoria, extrapyramidal symptoms, hallucinations, headache, hypomania, incoordination, increased and decreased libido, poor concentration, tingling and paresthesias of the extremities, syncope.

Dermatologic

Alopecia, photosensitization, pruritus, skin rash, urticaria.

EENT

Disturbances in accommodation, mydriasis.

GI

Anorexia, black tongue, diarrhea, epigastric distress, nausea, paralytic ileus, peculiar taste, stomatitis, vomiting.

Genitourinary

Breast enlargement, dilatation of the urinary tract, galactorrhea, gynecomastia and testicular swelling, minor menstrual irregularities, urinary frequency, urinary retention.

Hematologic-Lymphatic

Bone marrow depression, including agranulocytosis, eosinophilia, purpura, and thrombocytopenia.

Hepatic

Jaundice.

Metabolic-Nutritional

Increased and decreased blood sugar levels, SIADH secretion, weight gain or loss.

Miscellaneous

Edema of face and tongue, increased perspiration, parotid swelling.

Precautions

Warnings

Antidepressants increased the risk of suicidal thinking in short-term studies in children and adolescents. When considering the use of chlordiazepoxide/amitriptyline, balance the risk with clinical need. Observe children or adolescents closely for suicidal thinking and behavior, clinical worsening, or unusual changes in behavior. Advise families and caregivers of the need for close observation and communication with the health care provider.


Monitor

Periodically monitor liver function and CBC in patients on chronic treatment.


Pregnancy

Pregnancy category undetermined.

Lactation

Excreted in breast milk. Note: Each ingredient is excreted in breast milk.

Children

Safety and efficacy not established.

Elderly

Limit dosage to smallest effective amount to decrease risk of anticholinergic effects, ataxia, confusion, or oversedation.

Special Risk Patients

Use with caution in patients with history of angle-closure glaucoma or increased IOP, CV disorders, hepatic or renal function impairment, seizures, urethral spasm, or urinary retention; hyperthyroid patients or those receiving thyroid medication; and schizophrenic or paranoid patients.

Debilitated patients

Limit dosage to smallest effective amount to decrease risk of anticholinergic effects, ataxia, confusion, or oversedation.

Drug dependence

Withdrawal symptoms, including abdominal and muscle cramps, seizures, sweating, tremor, and vomiting, can occur with abrupt discontinuation of chlordiazepoxide.

Overdosage

Symptoms

Agitation, arrhythmias, CHF, coma, dilated pupils, drowsiness, hyperactive reflexes, hyperpyrexia, hypotension, hypothermia, muscle rigidity, seizures, stupor, tachycardia, temporary confusion, visual hallucinations, vomiting.

Patient Information

  • Advise patient to read the Medication Guide before using product the first time and with each refill.
  • Instruct patient to avoid intake of alcoholic beverages and other CNS depressants because additive effects can cause dangerous level of sedation and CNS depression.
  • Advise patient that drug may cause drowsiness and to use caution while driving or performing other tasks requiring alertness.
  • Instruct patient not to discontinue medication abruptly or change dosage without consulting with health care provider because withdrawal symptoms can occur.
  • Caution patient to avoid excessive exposure to sunlight and to use sunscreen or wear protective clothing to avoid photosensitivity reaction.
  • Advise patient that dry mouth may occur and that it may be relieved by taking sips of water frequently, sucking on hard sugarless candy, or chewing gum.
  • Advise patient, family, and caregiver to be alert for abnormal changes in mood or thinking and to immediately report any of the following to health care provider: agitation, anxiety, change in mood, change in personality, hostility or aggressiveness, impulsivity, insomnia, irritability, panic attacks, psychomotor restlessness, or suicidal thoughts or behavior. Observe patients for emergence on a day-to-day basis because changes may be abrupt.

Copyright © 2009 Wolters Kluwer Health.

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