Indicated for the treatment of patients with moderate to severe depression associated with moderate to severe anxiety.

The therapeutic response to chlordiazepoxide and amitriptyline hydrochloride tablets occur earlier and with fewer treatment failures than when either amitriptyline or chlordiazepoxide is used alone.

Symptoms likely to respond in the first week of treatment include: insomnia, feelings of guilt or worthlessness, agitation, psychic and somatic anxiety, suicidal ideation and anorexia.

It should be noted that LIMBITROL is not approved for use in treating bipolar depression. In patients with bipolar disorder, treating a depressive episode with Limbitrol or another antidepressant may precipitate a mixed/manic episode. Prior to initiating treatment with Limbitrol, screen patients for any personal or family history of bipolar disorder, mania, or hypomania.

The drug should be discontinued several days before elective surgery.

Antidepressants increased the risk compared to placebo of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults in short-term studies of major depressive disorder (MDD) and other psychiatric disorders. 

Concomitant use of benzodiazepines and opioids may result in profound sedation, respiratory depression, coma, and death. Reserve concomitant prescribing of these drugs for patients for whom alternative treatment options are inadequate. Limit dosages and durations to the minimum required. Follow patients for signs and symptoms of respiratory depression and sedation.

The use of benzodiazepines, including LIMBITROL, exposes users to risks of abuse, misuse, and addiction, which can lead to overdose or death. Abuse and misuse of benzodiazepines commonly involve concomitant use of other medications, alcohol, and/or illicit substances, which is associated with an increased frequency of serious adverse outcomes. Before prescribing LIMBITROL and throughout treatment, assess each patient’s risk for abuse, misuse, and addiction.

The continued use of benzodiazepines, including LIMBITROL, may lead to clinically significant physical dependence. The risks of dependence and withdrawal increase with longer treatment duration and higher daily dose. Abrupt discontinuation or rapid dosage reduction of LIMBITROL after continued use may precipitate acute withdrawal reactions, which can be life-threatening. To reduce the risk of withdrawal reactions, use a gradual taper to discontinue LIMBITROL or reduce the dosage.

In some cases, benzodiazepine users have developed a protracted withdrawal syndrome with withdrawal symptoms lasting weeks to more than 12 months.

Advise both patients and caregivers about the risks of respiratory depression and sedation when chlordiazepoxide and amitriptyline hydrochloride tablets are used with opioids. Advise patients not to drive or operate heavy machinery until the effects of concomitant use with the opioid have been determined.

Close supervision is required when LIMBITROL is given to hyperthyroid patients or those on thyroid medication.

Myocardial infarction and stroke have been reported in patients receiving drugs of this class.

Patients with cardiovascular disorders should be watched closely. Tricyclic antidepressant drugs, particularly when given in high doses, have been reported to produce arrhythmias, sinus tachycardia and prolongation of conduction time. 

Because of the atropine-like action of the amitriptyline component, great care should be used in treating patients with a history of urinary retention or angle closure glaucoma.

The pupillary dilation that occurs following use of many antidepressant drugs including chlordiazepoxide and amitriptyline hydrochloride tablets may trigger an angle-closure attack in a patient with anatomically narrow angles who does not have a patent iridectomy.

Granulocytopenia, jaundice and hepatic dysfunction of uncertain etiology have also been observed rarely with chlordiazepoxide and amitriptyline hydrochloride tablets. When treatment with chlordiazepoxide and amitriptyline hydrochloride tablets is prolonged, periodic blood counts and liver function tests are advisable.

LIMBITROL is contraindicated in patients with hypersensitivity to either benzodiazepines or tricyclic antidepressants.

LIMBITROL should not be given concomitantly with a monoamine oxidase inhibitor. Hyperpyretic crises, severe convulsions and deaths have occurred in patients receiving a tricyclic antidepressant and a monoamine oxidase inhibitor simultaneously. When it is desired to replace a monoamine oxidase inhibitor with chlordiazepoxide and amitriptyline hydrochloride tablets, a minimum of 14 days should be allowed to elapse after the former is discontinued.

LIMBITROL is contraindicated during the acute recovery phase following myocardial infarction.

Some patients may experience a large increase in amitriptyline concentration in the presence of topiramate and any adjustments in amitriptyline dose should be made according to the patient’s clinical response and not on the basis of plasma levels.

Because of its amitriptyline component, chlordiazepoxide and amitriptyline hydrochloride tablets may block the antihypertensive action of guanethidine or compounds with a similar mechanism of action.

An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines, and the type 1c antiarrhythmics propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., fluoxetine, sertraline and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition.

Cimetidine is reported to reduce hepatic metabolism of certain tricyclic antidepressants and benzodiazepines, thereby delaying elimination and increasing steady-state concentrations of these drugs.

Clinically significant effects have been reported with the tricyclic antidepressants when used concomitantly with cimetidine (Tagamet).

Concurrent administration of ECT and LIMBITROL should be limited to those patients for whom it is essential.

An increased risk of congenital malformations associated with the use of minor tranquilizers (chlordiazepoxide, diazepam and meprobamate) during the first trimester of pregnancy has been suggested in several studies. Because use of these drugs is rarely a matter of urgency, their use during this period should almost always be avoided.

It is not known whether this drug is excreted in human milk. As a general rule, nursing should not be undertaken while a patient is on a drug, since many drugs are excreted in human milk.

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• Use in patients under the age of 18. GoToSource

• Chronic neuropathic pain. GoToSource

• Irritable bowel syndrome. GoToSource

• Diabetic neuropathy. GoToSource

• Chronic fatigue syndrome. GoToSource

• Prevention of syncopal episodes. GoToSource

• Psychotic states in patients with down’s syndrome. GoToSource

• Gastrointestinal pain disorders including refractory functional dyspepsia. GoToSource

• Interstitial cystitis. GoToSource

• Vulvodynia. GoToSource

⚠️  Patients with CYP2D6 or CYP2C19 gene variation are at increased risk of treatment failure or side effects with Amitriptyline component of LIMBITROL.

Suicidal ideation and behavior. GoToSource

Arrhythmia, myocardial infarction and strokes. GoToSource

Delirium, cognitive decline, dementia and mortality. GoToSource

Reported as an inappropriate drug for elderly patients. GoToSource

Rhabdomyolysis with myoglobinuria (destruction or degeneration of muscle tissue) and acute kidney failure. GoToSource

Acute angle closure glaucoma. GoToSource

Weight gain, blurred vision, dry mouth and urinary retention. GoToSource

Congenital malformations when used during the first trimester of pregnancy. GoToSource

Lawsuits filed for birth defects.