Chlordiazepoxide and Amitriptyline (Systemic )


VA CLASSIFICATION
Primary: CN900

Note: Controlled substance classification—

Note: Controlled substance classification


U.S.—Schedule IV
Commonly used brand name(s): Limbitrol; Limbitrol DS.

Note: For a listing of dosage forms and brand names by country availability, see Dosage Forms section(s).

Not commercially available in Canada.



Category:


Antianxiety agent–antidepressant—

Indications

Accepted

Anxiety associated with mental depression (treatment)—The combination of chlordiazepoxide and amitriptyline is indicated in the treatment of moderate to severe anxiety associated with moderate to severe depression {03} {04}.
—The therapeutic response to chlordiazepoxide and amitriptyline combination may occur earlier than when either agent is used alone {01} {03} {04}. Symptoms most likely to respond to therapy in the first week are feelings of guilt or worthlessness, insomnia, agitation, anxiety, suicidal thoughts, and anorexia {01} {03} {04}.


Pharmacology/Pharmacokinetics

Physicochemical characteristics:
Molecular weight—
    Chlordiazepoxide hydrochloride: 336.22
    Amitriptyline hydrochloride: 313.87

Mechanism of action/Effect:

Chlordiazepoxide—In general, benzodiazepines, such as chlordiazepoxide, act as depressants of the central nervous system (CNS), producing all levels of CNS depression from mild sedation to hypnosis to coma depending on dose.

Amitriptyline—Although the exact mechanism of action in the treatment of depression is unclear, tricyclic antidepressants, such as amitriptyline, are thought to increase the synaptic concentration of norepinephrine (levarterenol; NE) and/or serotonin (5-hydroxytryptamine; 5-HT) in the central nervous system (CNS). One theory suggests that these neurotransmitters are increased through inhibition of their reuptake by the presynaptic neuronal membrane. Amitriptyline appears to be more potent in blocking serotonin, although, through its metabolites, it becomes a powerful inhibitor of norepinephrine reuptake also.

Absorption:

Chlordiazepoxide—Well absorbed from the gastrointestinal tract, usually within 1 to 2 hours.

Amitriptyline—Rapidly and well absorbed after oral administration.

Protein binding:

Chlordiazepoxide—Very high (96%).

Amitriptyline—Very high (96%).

Biotransformation:

Chlordiazepoxide—Hepatic.

Amitriptyline—Exclusively hepatic, with first-pass effect.

Half-life:

Chlordiazepoxide—5 to 30 hours.

Amitriptyline—8 to 93 hours (includes metabolites).

Onset of action:

Amitriptyline—2 to 3 weeks.

Elimination:
    Chlordiazepoxide—Renal.
    Amitriptyline—As metabolites, primarily renal, over several days; not dialyzable because of high protein binding.


Precautions to Consider

Cross-sensitivity and/or related problems

Patients sensitive to other benzodiazepines or tricyclic antidepressants may be sensitive to this medication also.

Pregnancy/Reproduction

Pregnancy—

For chlordiazepoxide

Chlordiazepoxide crosses the placenta. Chronic use during pregnancy may cause physical dependence with resulting withdrawal symptoms in the neonate.

First trimester: Chlordiazepoxide has been reported to increase the risk of congenital malformations when used during the first trimester of pregnancy. Since use of chlordiazepoxide is rarely a matter of urgency, its use during pregnancy, especially during the first trimester, should be avoided. {03} {04}



For amitriptyline

Adequate and well-controlled studies have not been done in humans.

Animal studies have shown amitriptyline to cause teratogenic effects when used in doses many times the human dose.

FDA Pregnancy Category C.


Labor—

For chlordiazepoxide: Use of chlordiazepoxide just prior to or during labor may cause neonatal flaccidity.

Delivery—

For amitriptyline: There have been reports of infants suffering cardiac problems, muscle spasms, respiratory distress, and urinary retention when their mothers received tricyclic antidepressants immediately prior to delivery.

Breast-feeding

Chlordiazepoxide—Chlordiazepoxide and its metabolites are excreted in breast milk. Since neonates metabolize chlordiazepoxide more slowly than adults and accumulation of chlordiazepoxide and its metabolites may occur, use by nursing mothers may cause sedation and possibly feeding difficulties and weight loss in the infant.

Amitriptyline—Problems in nursing babies have not been documented; however, amitriptyline has been found in breast milk with unknown effects.

Pediatrics

Appropriate studies on the relationship of age to the effects of chlordiazepoxide and amitriptyline combination have not been performed in children up to 12 years of age. However, adolescent patients are likely to exhibit dose sensitivity, and may require a lower initial dose.


Geriatrics


Elderly and debilitated patients are often less able to metabolize the components of this combination and tend to develop central nervous system (CNS) and anticholinergic side effects at lower than normal doses. Close supervision is necessary for patients with cardiac problems, glaucoma, urinary retention, and/or gastrointestinal problems. A lower initial dose may be necessary. Also, patients in this group may not tolerate the larger single doses given once a day but may tolerate a divided dosage.


Dental

The peripheral anticholinergic effects of chlordiazepoxide and amitriptyline combination may decrease or inhibit salivary flow, especially in middle-aged or elderly patients, thus contributing to the development of caries, periodontal disease, oral candidiasis, and discomfort.

The leukopenic and thrombocytopenic effects of amitriptyline may result in an increased incidence of microbial infection, delayed healing, and gingival bleeding. If leukopenia or thrombocytopenia occurs, dental work should be deferred until blood counts have returned to normal. Patient instruction in proper oral hygiene should include caution in use of regular toothbrushes, dental floss, and toothpicks.

Drug interactions and/or related problems
The following drug interactions and/or related problems have been selected on the basis of their potential clinical significance (possible mechanism in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):


Note: Combinations containing any of the following medications, depending on the amount present, may also interact with this medication.

» Addictive medications, other, especially CNS depressants with habituating potential    (prolonged concurrent use with chlordiazepoxide may increase the risk of habituation; caution is recommended)


» Alcohol{03}{04} or
» CNS depression–producing medications, other,{03}{04} (See Appendix II )    (concurrent use may increase the CNS depressant effects of either these medications or chlordiazepoxide or amitriptyline; caution is recommended, and dosage of one or both agents should be reduced)

    (when chlordiazepoxide is used concurrently with an opioid analgesic, the dosage of the opioid analgesic should be reduced by at least one-third and administered in small increments)

    (amitriptyline may enhance the response to alcohol, especially during the first few days of treatment; in patients who use alcohol excessively, amitriptyline may increase the danger inherent in any suicide attempt)


Amantadine or
Anticholinergics or other medications with anticholinergic action{03}{04} (See Appendix II ) or
Antidyskinetic agents or
Antihistamines    (concurrent use with amitriptyline may potentiate the anticholinergic effects, especially confusion, hallucinations, and nightmares; dosage adjustments of either medication may be necessary)

    (concurrent use may potentiate the CNS depressant effects of either antihistamines or chlordiazepoxide or amitriptyline)

    (concurrent use with amitriptyline may block detoxification of atropine and related compounds; patients should be advised to report occurrence of gastrointestinal problems promptly since paralytic ileus may occur with concurrent therapy)


» Antacids    (concurrent use may delay, but not reduce, the absorption of chlordiazepoxide)


Anticoagulants, coumarin- or indandione-derivative    (concurrent use with amitriptyline may cause an increase in anticoagulant activity by inhibiting enzymatic metabolism of anticoagulant)


Anticonvulsants    (amitriptyline may enhance CNS depression, lower the seizure threshold, and decrease the effects of the anticonvulsant medication; dosage adjustments may be necessary to control seizures)


» Antithyroid agents    (concurrent use with amitriptyline may increase the risk of agranulocytosis)


Barbiturates    (when barbiturates, especially phenobarbital, are used concurrently with amitriptyline, the effects of amitriptyline may be decreased because of increased metabolism resulting from induction of hepatic microsomal enzymes)


» Cimetidine{03}{04}    (concurrent use may inhibit amitriptyline and chlordiazepoxide metabolism and increase plasma concentrations, leading to toxicity)


» Clonidine or
» Guanadrel or
» Guanethidine{03}{04}    (concurrent use with amitriptyline may decrease the hypotensive effects of these medications)

    (concurrent use of clonidine with chlordiazepoxide and amitriptyline combination may result in potentiation of CNS depressant effects)


Contraceptives, oral, estrogen-containing or
Estrogens, including estramustine    (concurrent use may decrease therapeutic effects of amitriptyline; however, these medications may also increase plasma concentrations of amitriptyline, leading to toxicity; dosage reduction of amitriptyline may be necessary)

    (concurrent long-term use of oral contraceptives with chlordiazepoxide may result in reduced contraceptive reliability and an increased incidence of breakthrough bleeding)


Cyclobenzaprine or
Haloperidol or
Loxapine or
Maprotiline or
Phenothiazines or
Thioxanthenes    (concurrent use may prolong and intensify the sedative and anticholinergic effects of either these medications or amitriptyline and chlordiazepoxide)

    (when used concurrently with phenothiazines, serum concentrations of amitriptyline may be increased due to inhibition of metabolism)


Disulfiram or
Ethchlorvynol    (concurrent use with amitriptyline may result in transient delirium)

    (CNS depressant effects may be increased when ethchlorvynol is used concurrently with chlordiazepoxide and amitriptyline combination)


Electroconvulsive therapy{03}{04}    (hazards may be increased with use of chlordiazepoxide and amitriptyline combination)


Fenfluramine    (concurrent use may potentiate the sedative effects of either fenfluramine or chlordiazepoxide and amitriptyline combination)


Fluoxetine{06}{07}    (concurrent use of fluoxetine with tricyclic antidepressants has produced increased plasma concentrations of the tricyclic antidepressant, possibly due to inhibition of tricyclic antidepressant metabolism; in addition, concurrent use may increase the CNS depressant effects of both medications; caution is recommended, and dosage of one or both agents should be reduced)


Levodopa    (concurrent use with chlordiazepoxide may decrease the therapeutic effects of levodopa)


Methylphenidate    (serum concentrations of amitriptyline may be increased due to inhibition of metabolism when methylphenidate is used concurrently; also, concurrent use may antagonize the effects of methylphenidate)


» Metrizamide    (concurrent use of amitriptyline with intrathecal administration of metrizamide may increase risk of seizures because amitriptyline lowers the seizure threshold; it is recommended that amitriptyline be discontinued for at least 48 hours before and 24 hours after myelography)


» Monoamine oxidase (MAO) inhibitors{03}{04} , including furazolidone, procarbazine, and selegiline    (in addition to possibly increasing CNS depressant effects with chlordiazepoxide and amitriptyline combination, concurrent use with amitriptyline is not recommended, especially on an outpatient basis, because hyperpyretic episodes, severe seizures, hypertensive crises, and death have resulted; at least 2 weeks should elapse between discontinuing one medication and initiating the other)


Naphazoline, ophthalmic or
Oxymetazoline, nasal or
Phenylephrine, nasal or ophthalmic or
Xylometazoline, nasal    (if significant systemic absorption occurs, concurrent use with amitriptyline may potentiate pressor effects of these medications)


Pimozide    (concurrent use with amitriptyline may potentiate cardiac arrhythmias)


» Sympathomimetics    (concurrent use with amitriptyline may potentiate cardiovascular effects, possibly resulting in arrhythmias, tachycardia, or severe hypertension or hyperpyrexia)

    (significant systemic absorption of ophthalmic epinephrine may also potentiate cardiovascular effects; local anesthetics with epinephrine or levonordefrin should also be avoided)

    (concurrent use of ephedrine and mephentermine with amitriptyline may decrease the pressor effect of these medications)


Thyroid hormones    (concurrent use with amitriptyline may increase the possibility of cardiac arrhythmias and enhance the antidepressant response; also the onset of action of amitriptyline may be accelerated; dosage adjustments may be necessary, although the problem is reduced in euthyroid patients)



Laboratory value alterations
The following have been selected on the basis of their potential clinical significance (possible effect in parentheses where appropriate)—not necessarily inclusive (» = major clinical significance):

With diagnostic test results
Metyrapone test    (response to metyrapone may be decreased {05})

With physiology/laboratory test values
Blood sugar concentrations    (may be increased or decreased {03} {04})


Medical considerations/Contraindications
The medical considerations/contraindications included have been selected on the basis of their potential clinical significance (reasons given in parentheses where appropriate)— not necessarily inclusive (» = major clinical significance).


Except under special circumstances, this medication should not be used when the following medical problem exists:
» Myocardial infarction, during the acute recovery period{03}{04}
Risk-benefit should be considered when the following medical problems exist
» Alcoholism, active or in remission{04}    (CNS depression may be potentiated and risk of addiction to alcohol or chlordiazepoxide may be increased)


» Bipolar disorder    (swing to manic or hypomanic phase may be accelerated)


» Blood disorders    (may be potentiated)


» Cardiovascular disorders{03}{04} , especially in the elderly    (increased risk of arrhythmias, heart block, congestive heart failure, myocardial infarction, or stroke)


Drug abuse or dependence, history of{04}    (predisposition of patients to habituation and dependence)


» Epilepsy or seizure disorders{03}{04}    (seizure threshold may be lowered)


» Gastrointestinal disorders    (risk of paralytic ileus, especially in the elderly)


» Glaucoma, narrow-angle form or predisposition to{03}{04}    (may be aggravated)


» Hepatic function impairment{03}{04}    (elimination half-life may be prolonged)


Hyperkinesis    (paradoxical reactions may occur)


» Hyperthyroidism{03}{04}    (risk of cardiovascular toxicity)


Hypoalbuminemia    (may dispose patient to increased incidence of sedative side effects)


Myasthenia gravis or
Porphyria    (condition may be exacerbated)


» Prostatic hypertrophy    (risk of urinary retention)


» Psychosis, latent    (may be activated)


Pulmonary disease, severe chronic obstructive    (ventilatory failure may be exacerbated)


Renal function impairment{03}{04}    (excretion may be prolonged)


Sensitivity to chlordiazepoxide or amitriptyline
» Urinary retention{03}{04}    (may be aggravated)



Patient monitoring
The following may be especially important in patient monitoring (other tests may be warranted in some patients, depending on condition; » = major clinical significance):

Blood cell counts{03}{04} and
Blood pressure determinations and
Cardiac function monitoring and
Hepatic function determinations{03}{04}    (may be required at periodic intervals for patients on prolonged therapy to detect signs of adverse effects)


Reassessment of medication's efficacy    (recommended at periodic intervals during therapy)




Side/Adverse Effects
The following side/adverse effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)—not necessarily inclusive:

Those indicating need for medical attention
Incidence less frequent
    
Aggravation of glaucoma (blurred vision or other changes in vision; eye pain)
    
anticholinergic effects (blurred vision{03}{04}; constipation{03}{04} or paralytic ileus{03}{04} , especially in the elderly; difficulty in urination{03}{04})
    
CNS stimulation, paradoxical (trouble in sleeping; unusual excitement, nervousness, or irritability)
    
confusion, delirium, or hallucinations {03}{04}
    
hypotension{03}{04} (fainting)
    
irregular heartbeat{03}{04}
    
mental depression
    
muscle tremors{03}{04} (shakiness)

Incidence rare
    
Agranulocytosis{03}{04} (sore throat and fever)
    
allergic reaction{03}{04} (increased sensitivity to sunlight; skin rash and itching)
    
cholestatic jaundice{03}{04} (yellow eyes or skin)
    
convulsions



Those indicating need for medical attention only if they continue or are bothersome
Incidence more frequent
    
Bloating{03}{04}
    
clumsiness or unsteadiness{03}{04}
    
drowsiness{03}{04}
    
dryness of mouth or unpleasant taste{03}{04}
    
headache
    
orthostatic hypotension{03}{04} (dizziness or lightheadedness)
    
weight gain{03}{04}

Incidence less frequent
    
Nausea
vomiting
or diarrhea {03}{04}
    
unusual tiredness or weakness



Those indicating possible withdrawal and the need for medical attention if they occur after medication is discontinued (usually within 2 weeks)
    
Convulsions{04}
    
headache{01}{03}{04}
    
increased sweating{04}
    
irritability or restlessness
    
muscle cramps{04}
    
nausea or vomiting{03}{04}
    
stomach cramps{04}
    
trembling{04}
    
trouble in sleeping, with vivid dreams{04}




Overdose
For specific information on the agents used in the management of chlordiazepoxide and amitriptyline overdose, see:
   • Charcoal, Activated (Oral-Local) monograph;
   • Dopamine, Metaraminol, and Norepinephrine in Sympathomimetic Agents–Cardiovascular Use (Parenteral-Systemic) monograph;
   • Digitalis Glycosides (Systemic) monograph;
   • Lidocaine (Systemic) monograph;
   • Phenytoin in Anticonvulsants, Hydantoin (Systemic) monograph;
   • Propranolol in Beta-adrenergic Blocking Agents (Systemic) monograph;
   • Sodium Bicarbonate (Systemic) monograph.
For more information on the management of overdose or unintentional ingestion, contact a Poison Control Center (see Poison Control Center Listing ).

Clinical effects of overdose
The following effects have been selected on the basis of their potential clinical significance (possible signs and symptoms in parentheses where appropriate)–not necessarily inclusive:
    
Agitation{03}{04}
    
confusion{03}{04}
    
convulsions{03}{04}
    
dizziness or lightheadedness, severe{03}{04}
    
drowsiness, severe{03}{04}
    
enlarged pupils{03}{04}
    
fast or irregular heartbeat{03}{04}
    
fever{03}{04}
    
hallucinations{03}{04}
    
muscle stiffness or rigidity{03}{04}
    
vomiting, severe{01}{03}{04}


Treatment of overdose
Because no specific antidote is available for acute overdose of this combination, treatment is essentially symptomatic and supportive and includes:


To decrease absorption:
Emptying stomach with lavage {03} {04}.

Administering activated charcoal slurry {03} {04} followed by a saline cathartic.



To enhance elimination:
Dialysis of either of the two components has not been successful because of their high protein binding {03} {04}.



Specific treatment:
Controlling hypotension, if necessary, by intravenous administration of vasopressors such as dopamine, norepinephrine, or metaraminol.

Digitalizing cautiously for congestive heart failure {03}.

Controlling cardiac arrhythmias with lidocaine or by alkalinizing blood to pH 7.4 to 7.5 with intravenous sodium bicarbonate. Arrhythmias refractory to sodium bicarbonate may be managed with slow intravenous infusion of phenytoin. Propranolol is also effective but should be used with caution because of its negative inotropic and hypotensive effects. Quinidine and procainamide should be avoided.

Controlling seizures with an inhalation anesthetic {03} {04}.

If excitation occurs, barbiturates should not be used since they may exacerbate excitation and/or prolong CNS depression.



Monitoring:
Monitoring cardiovascular function {03} {04}, electrocardiogram (ECG) for not less than 5 days.

Monitoring serum potassium concentrations and maintaining within normal limits with the appropriate intravenous fluids {03} {04}.



Supportive care:
Maintaining respiratory {03} {04} and cardiac function.

Maintaining body temperature because hypothermia or hyperpyrexia may occur {03} {04}.

Using standard measures to manage circulatory shock and metabolic acidosis {03} {04}.

Patients in whom intentional overdose is known or suspected should be referred for psychiatric consultation.



Patient Consultation
As an aid to patient consultation, refer to Advice for the Patient, Chlordiazepoxide and Amitriptyline (Systemic).

In providing consultation, consider emphasizing the following selected information (» = major clinical significance):

Before using this medication
»   Conditions affecting use, especially:
Sensitivity to other benzodiazepines or tricyclic antidepressants

Pregnancy—Chlordiazepoxide: Crosses placenta; chronic use may cause physical dependence in mother and withdrawal symptoms in neonate; reported to increase risk of congenital malformations when used during first trimester; during delivery, may cause neonatal flaccidity when used just prior to or during labor

Amitriptyline: Animal studies have shown teratogenic effects when given in doses many times larger than the human dose; reports of cardiac problems, muscle spasms, respiratory distress, or urinary retention in neonates of mothers taking amitriptyline just prior to delivery





Breast-feeding—Chlordiazepoxide excreted in breast milk; may cause sedation, feeding difficulties, or weight loss in infant





Use in children—Adolescents are more likely to exhibit dose sensitivity to chlordiazepoxide and amitriptyline combination, requiring a lower initial dose






Use in the elderly—Elderly tend to develop CNS and anticholinergic effects at lower doses; close supervision necessary for patients with cardiac problems, glaucoma, urinary retention, and/or gastrointestinal problems; elderly may better tolerate divided doses





Dental—Dryness of mouth may contribute to development of caries, periodontal disease, oral candidiasis, and discomfort; possible dyscrasias caused by amitriptyline may increase incidence of microbial infection, delayed healing, and gingival bleeding
Other medications, especially other addictive medications, antacids, antithyroid agents, cimetidine, clonidine, guanadrel, guanethidine, alcohol or other CNS depression-producing medications, monoamine oxidase (MAO) inhibitors, metrizamide, or sympathomimetics
Other medical problems, especially alcoholism, active or in remission; seizure disorders; glaucoma; hepatic function impairment; latent psychosis; bipolar disorder; blood, cardiovascular, or gastrointestinal disorders; hyperthyroidism; prostatic hypertrophy; or urinary retention

Proper use of this medication
Taking after meals or with food to reduce gastric irritation

» Several weeks of therapy may be required to produce optimal therapeutic effects.

» Importance of not taking more medication than the amount prescribed because of habit-forming potential

» Not increasing dose if medication is less effective after a few weeks; checking with physician

» Proper dosing
Missed dose: Not taking dose at all; continuing on schedule; not doubling doses

» Proper storage

Precautions while using this medication
Regular visits to physician to check progress of therapy

» Checking with physician before discontinuing medication; gradual dosage reduction may be needed to avoid the possibility of withdrawal symptoms

» Avoiding use of alcoholic beverages or other CNS depressants during therapy; not taking other medication unless discussed with physician

Diabetics: May affect blood sugar determinations

Caution if any laboratory tests required; possible interference with results of metyrapone test

» Caution if any kind of surgery, dental treatment, or emergency treatment is required

» Possible drowsiness; caution when driving or doing things requiring alertness {03} {04}

» Possible dizziness; caution when getting up suddenly from a lying or sitting position

Possible dryness of mouth; using sugarless candy or gum, ice, or saliva substitute for relief; checking with dentist or physician if dry mouth continues for more than 2 weeks

Possible skin photosensitivity; avoiding unprotected exposure to sun; using protective clothing; using a sun block product that includes protection against both UVA-caused photosensitivity reactions and UVB-caused sunburn reactions; avoiding use of sunlamp, tanning bed, or tanning booth


Side/adverse effects
Signs of potential side effects, especially aggravation of glaucoma, agranulocytosis, allergic reactions, anticholinergic effects, convulsions, hallucinations, hypotension, irregular heartbeat, jaundice, mood or mental changes, muscle tremors, or paradoxical CNS stimulation


General Dosing Information
Geriatric and adolescent patients are more likely to exhibit dose sensitivity; therefore, a lower initial dose should usually be used for these patients.

Although a sedative action may occur following the initial dose, up to 30 days may be required before the desired antidepressant response is obtained.

For maintenance therapy, the daily dose may be reduced somewhat and given as a single dose at bedtime. This therapy is often continued for 6 months to 1 year. A divided dose may be preferred, however, for geriatric, adolescent, or cardiovascular patients.

Because amitriptyline is considered among the most sedative of the tricyclic antidepressants, the single daily dose at bedtime may be utilized for selected patients.

Potentially suicidal patients should not have access to large quantities of this medication since depressed patients, particularly those who may use alcohol excessively, may continue to exhibit suicidal tendencies until significant improvement occurs {03} {04}.

Prolonged use or larger-than-usual therapeutic doses of chlordiazepoxide may result in psychic or physical dependence.

Withdrawal symptoms of headache, nausea, and malaise may occur if high or prolonged dosage is abruptly discontinued {04}. A gradual reduction in dosage {04} over a 1- or 2-month period is recommended.

Diet/Nutrition
Dose may be taken with or immediately following meals to lessen gastric irritation.

The requirements for riboflavin may be increased in patients receiving amitriptyline {02}.


Oral Dosage Forms

CHLORDIAZEPOXIDE AND AMITRIPTYLINE HYDROCHLORIDE TABLETS USP

Usual adult and adolescent dose
Antianxiety agent–antidepressant
Oral, 5 mg of chlordiazepoxide and 12.5 mg of amitriptyline hydrochloride or 10 mg of chlordiazepoxide and 25 mg of amitriptyline hydrochloride three or four times a day initially, the dosage being adjusted as needed and tolerated {03} {04}.


Note: The larger portion of the daily dose may be taken at bedtime. A single bedtime dose may be adequate for some patients. {03} {04}


Usual adult prescribing limits
10 mg of chlordiazepoxide and 25 mg of amitriptyline hydrochloride up to six times a day {04}.

Usual pediatric dose
Antianxiety agent–antidepressant
Children up to 12 years of age: Dosage has not been established {03} {04}.

Children 12 years of age and over: See Usual adult and adolescent dose.


Strength(s) usually available
U.S.—


5 mg of chlordiazepoxide and 12.5 mg of amitriptyline hydrochloride (Rx) [Limbitrol][Generic]


10 mg of chlordiazepoxide and 25 mg of amitriptyline hydrochloride (Rx) [Limbitrol DS][Generic]

Canada—
Not commercially available.

Packaging and storage:
Store below 40 °C (104 °F), preferably between 15 and 30 °C (59 and 86 °F), unless otherwise specified by manufacturer. Store in a tight, light-resistant container.

Auxiliary labeling:
   • May cause drowsiness.
   • Avoid alcoholic beverages.

Note: Controlled substance in the U.S.




Revised: 03/19/1993



References

Note: All references used in the development and earlier revisions of this monograph have not yet been incorporated into the computer database and, therefore, are not listed below. Citations for information not yet referenced in the monograph will be provided upon request.

  1. Limbitrol (Roche) package insert, Rev 9/85.
  1. Pinto JT, Rivlin RS. Drugs that promote renal excretion of riboflavin. Drug Nutr Interact 1987; 5(3): 143-51.
  1. Package insert (Mylan), Rev 10/88, Rec 3/89.
  1. Limbitrol (Roche) monograph, PDR 1990: 1823-4.
  1. Metyrapone monograph, USP DI 1991.
  1. Fluoxetine (Prozac) package insert, Rev 6/20/89.
  1. Fluoxetine (Prozac) revisited. Med Lett Drugs Ther (Sep 7) 1990; 32(826): 83-5.
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