Chlordiazepoxide amitriptyline: Depression Drug Warnings

Generic drug: chlordiazepoxide amitriptyline ds

Brand name: Limbitrol

What is Limbitrol (chlordiazepoxide amitriptyline ds), and how does it work?

Limbitrol is a prescription medicine used to treat moderate to severe depression that can happen with moderate to severe anxiety.
Limbitrol is a federally controlled substance (C-IV) because it contains chlordiazepoxide that can be abused or lead to dependence. Keep Limbitrol in a safe place to prevent misuse and abuse. Selling or giving away Limbitrol may harm others, and is against the law. Tell your healthcare provider if you have ever abused or been dependent on alcohol, prescription medicines or street drugs.
It is not known if Limbitrol is safe and effective in children.

What are the side effects of Limbitrol?

Suicidality and Antidepressant Drugs

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.
Anyone considering the use of Chlordiazepoxide and Amitriptyline Hydrochloride
Tablets or any other antidepressant in a child, adolescent, or young adult must
balance this risk with the clinical need.

Short-term studies did not show an
increase in the risk of suicidality with antidepressants compared to placebo in
adults beyond age 24; there was a reduction in the risk with antidepressants
compared to placebo in adults aged 65 and older. Depression and certain other
psychiatric disorders are themselves associated with increases in the risk of
suicide.

Patients of all ages who are started on antidepressant therapy should
be monitored appropriately and observed closely for clinical worsening,
suicidality, or unusual changes in behavior. Families and caregivers should be
advised of the need for close observation and communication with the prescriber.
Limbitrol is not approved for use in pediatric patients.

Limbitrol may cause serious side effects, including:

Limbitrol can make you sleepy or dizzy, and can slow your thinking and motor skills.
- Do not drive, operate heavy machinery, or do other dangerous activities until you know how Limbitrol affects you.
- Do not drink alcohol or take other drugs that may make you sleepy or dizzy while taking Limbitrol without first talking to your healthcare provider. When taken with alcohol or drugs that cause sleepiness or dizziness, Limbitrol may make your sleepiness or dizziness much worse.

The most common side effects of Limbitrol include:

drowsiness
constipation
dizziness
dry mouth
blurred vision
bloating

These are not all the possible side effects of Limbitrol.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

What is the dosage for Limbitrol?

Optimum dosage varies with the severity of the symptoms and the response of the individual patient. When a satisfactory response is obtained, dosage should be reduced to the smallest amount needed to maintain the remission. The larger portion of the total daily dose may be taken at bedtime. In some patients, a single dose at bedtime may be sufficient. In general, lower dosages are recommended for elderly patients.
Limbitrol DS (double strength) Tablets are recommended in an initial dosage of 3 or 4 tablets daily in divided doses; this may be increased to 6 tablets daily as required. Some patients respond to smaller doses and can be maintained on 2 tablets daily.
Limbitrol Tablets in an initial dosage of 3 or 4 tablets daily in divided doses may be satisfactory in patients who do not tolerate higher doses.

Screen For Bipolar Disorder Prior To Starting Limbitrol

Prior to initiating treatment with Limbitrol or another antidepressant,
screen patients for a personal or family history of bipolar disorder, mania,
or hypomania.

Discontinuation Or Dosage Reduction Of Limbitrol

To reduce the risk of withdrawal reactions, use a gradual taper to
discontinue Limbitrol or reduce the dosage. If a patient develops withdrawal
reactions, consider pausing the taper or increasing the dosage to the
previous tapered dosage level. Subsequently decrease the dosage more slowly.

Does Limbitrol cause addiction or withdrawal symptoms?

Drug Abuse And Dependence

Controlled Substance

Limbitrol contains chlordiazepoxide, a Schedule IV controlled substance.

Abuse

Limbitrol is a benzodiazepine and a CNS depressant with a potential for abuse and addiction. Abuse is the intentional, non-therapeutic use of a drug, even once, for its desirable psychological or physiological effects.
Misuse is the intentional use, for therapeutic purposes, of a drug by an individual in a way other than prescribed by a health care provider or for whom it was not prescribed.
Drug addiction is a cluster of behavioral, cognitive, and physiological phenomena that may include a strong desire to take the drug, difficulties in controlling drug use (e.g., continuing drug use despite harmful consequences, giving a higher priority to drug use than other activities and obligations), and possible tolerance or physical dependence. Even taking benzodiazepines as prescribed may put patients at risk for abuse and misuse of their medication. Abuse and misuse of benzodiazepines may lead to addiction.
Abuse and misuse of benzodiazepines often (but not always) involve the
use of doses greater than the maximum recommended dosage and commonly
involve concomitant use of other medications, alcohol, and/or illicit
substances, which is associated with an increased frequency of serious
adverse outcomes, including respiratory depression, overdose, or death.
Benzodiazepines are often sought by individuals who abuse drugs and other
substances, and by individuals with addictive disorders.
The following adverse reactions have occurred with benzodiazepine abuse and/or misuse: abdominal pain, amnesia, anorexia, anxiety, aggression, ataxia, blurred vision, confusion, depression, disinhibition, disorientation, dizziness, euphoria, impaired concentration and memory, indigestion, irritability, muscle pain, slurred speech, tremors, and vertigo.
The following severe adverse reactions have occurred with benzodiazepine abuse and/or misuse: delirium, paranoia, suicidal ideation and behavior, seizures, coma, breathing difficulty, and death. Death is more often associated with polysubstance use (especially benzodiazepines with other CNS depressants such as opioids and alcohol).

Dependence

Physical Dependence

Limbitrol may produce physical dependence from continued therapy.
Physical dependence is a state that develops as a result of physiological
adaptation in response to repeated drug use, manifested by withdrawal signs
and symptoms after abrupt discontinuation or a significant dose reduction of
a drug. Abrupt discontinuation or rapid dosage reduction of benzodiazepines
or administration of flumazenil, a benzodiazepine antagonist, may
precipitate acute withdrawal reactions, including seizures, which can be
life-threatening.
Patients at an increased risk of withdrawal adverse reactions after
benzodiazepine discontinuation or rapid dosage reduction include those who
take higher dosages (i.e., higher and/or more frequent doses) and those who
have had longer durations of use.
To reduce the risk of withdrawal reactions, use a gradual taper to
discontinue Limbitrol or reduce the dosage.

Acute Withdrawal Signs And Symptoms

Acute withdrawal signs and symptoms associated with benzodiazepines have included
- abnormal involuntary movements,
- anxiety,
- blurred vision,
- depersonalization,
- depression,
- derealization,
- dizziness,
- fatigue,
- gastrointestinal adverse reactions (e.g., nausea, vomiting, diarrhea, weight loss, decreased appetite),
- headache,
- hyperacusis,
- hypertension,
- irritability,
- insomnia,
- memory impairment,
- muscle pain and stiffness,
- panic attacks,
- photophobia,
- restlessness,
- tachycardia, and
- tremor.
More severe acute withdrawal signs and symptoms, including life-threatening reactions, have included
- catatonia,
- convulsions,
- delirium tremens,
- depression,
- hallucinations,
- mania,
- psychosis,
- seizures, and
- suicidality.

Protracted Withdrawal Syndrome

Protracted withdrawal syndrome associated with benzodiazepines is characterized by anxiety, cognitive impairment, depression, insomnia, formication, motor symptoms (e.g., weakness, tremor, muscle twitches), paresthesia, and tinnitus that persists beyond 4 to 6 weeks after initial benzodiazepine withdrawal.
Protracted withdrawal symptoms may last weeks to more than 12 months. As a result, there may be difficulty in differentiating withdrawal symptoms from potential re-emergence or continuation of symptoms for which the benzodiazepine was being used.

Tolerance

Tolerance to Limbitrol may develop from continued therapy. Tolerance is a physiological state characterized by a reduced response to a drug after repeated administration (i.e., a higher dose of a drug is required to produce the same effect that was once obtained at a lower dose).
Tolerance to the therapeutic effect of Limbitrol may develop; however, little tolerance develops to the amnestic reactions and other cognitive impairments caused by benzodiazepines.

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What drugs interact with Limbitrol?

Drug-Drug Interactions

The concomitant use of benzodiazepines and opioids increases the risk of respiratory depression because of actions at different receptor sites in the CNS that control respiration. Benzodiazepines interact at GABAA sites and opioids interact primarily at mu receptors.
When benzodiazepines and opioids are combined, the potential for benzodiazepines to significantly worsen opioid-related respiratory depression exists. Limit dosage and duration of concomitant use of benzodiazepines and opioids, and monitor patients closely for respiratory depression and sedation.

Topiramate

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.

Drug And Treatment Interactions

Because of its amitriptyline component, Limbitrol may block the antihypertensive action of guanethidine or compounds with a similar mechanism of action.

Drugs Metabolized By P450 2D6

The biochemical activity of the drug metabolizing isozyme cytochrome P450 2D6 (debrisoquin hydroxylase) is reduced in a subset of the Caucasian population (about 7% to 10% of Caucasians are so called “poor metabolizers”); reliable estimates of the prevalence of reduced P450 2D6 isozyme activity among Asian, African and other populations are not yet available.
Poor metabolizers have higher than expected plasma concentrations of tricyclic antidepressants (TCAs) when given usual doses. Depending on the fraction of drug metabolized by P450 2D6, the increase in plasma concentration may be small or quite large (8-fold increase in plasma AUC of the TCA).
In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. 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.
The extent to which SSRI TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the coadministration of TCAs with any of the SSRIs and also in switching from one class to the other.
Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).
Concomitant use of tricyclic antidepressants with drugs that can inhibit cytochrome P450 2D6 may require lower doses than usually prescribed for either the tricyclic antidepressant or the other drug. Furthermore, whenever one of these other drugs is withdrawn from cotherapy, an increased dose of tricyclic antidepressant may be required. It is desirable to monitor TCA plasma levels whenever a TCA is going to be coadministered with another drug known to be an inhibitor of P450 2D6.
The effects of concomitant administration of Limbitrol and other psychotropic drugs have not been evaluated. Sedative effects may be additive.
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).
The drug should be discontinued several days before elective surgery.
Concurrent administration of ECT and Limbitrol should be limited to those patients for whom it is essential.

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Depression is a(n) __________ .
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Is Limbitrol safe to use while pregnant or breastfeeding?

Safe use of Limbitrol during pregnancy and lactation has not been established. Because of the chlordiazepoxide component, please note the following:
- 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.
- The possibility that a woman of childbearing potential may be pregnant at the time of institution of therapy should be considered.
- Patients should be advised that if they become pregnant during therapy or intend to become pregnant they should communicate with their physicians about the desirability of discontinuing the drug.
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.