Chlordiazepoxide And Amitriptyline Hydrochloride


Mylan Pharmaceuticals Inc.
Human Prescription Drug
NDC 0378-0211
Chlordiazepoxide And Amitriptyline Hydrochloride is a human prescription drug labeled by 'Mylan Pharmaceuticals Inc.'. National Drug Code (NDC) number for Chlordiazepoxide And Amitriptyline Hydrochloride is 0378-0211. This drug is available in dosage form of Tablet, Film Coated. The names of the active, medicinal ingredients in Chlordiazepoxide And Amitriptyline Hydrochloride drug includes Amitriptyline Hydrochloride - 14 mg/1 Chlordiazepoxide - 5 mg/1 . The currest status of Chlordiazepoxide And Amitriptyline Hydrochloride drug is Active.

Drug Information:

Drug NDC: 0378-0211
The labeler code and product code segments of the National Drug Code number, separated by a hyphen. Asterisks are no longer used or included within the product code segment to indicate certain configurations of the NDC.
Proprietary Name: Chlordiazepoxide And Amitriptyline Hydrochloride
Also known as the trade name. It is the name of the product chosen by the labeler.
Product Type: Human Prescription Drug
Indicates the type of product, such as Human Prescription Drug or Human OTC Drug. This data element corresponds to the “Document Type” of the SPL submission for the listing.
Non Proprietary Name: Chlordiazepoxide And Amitriptyline Hydrochloride
Also known as the generic name, this is usually the active ingredient(s) of the product.
Labeler Name: Mylan Pharmaceuticals Inc.
Name of Company corresponding to the labeler code segment of the ProductNDC.
Dosage Form: Tablet, Film Coated
The translation of the DosageForm Code submitted by the firm. There is no standard, but values may include terms like `tablet` or `solution for injection`.The complete list of codes and translations can be found www.fda.gov/edrls under Structured Product Labeling Resources.
Status: Active
FDA does not review and approve unfinished products. Therefore, all products in this file are considered unapproved.
Substance Name:AMITRIPTYLINE HYDROCHLORIDE - 14 mg/1
CHLORDIAZEPOXIDE - 5 mg/1
This is the active ingredient list. Each ingredient name is the preferred term of the UNII code submitted.
Route Details:ORAL
The translation of the Route Code submitted by the firm, indicating route of administration. The complete list of codes and translations can be found at www.fda.gov/edrls under Structured Product Labeling Resources.

Marketing Information:

An openfda section: An annotation with additional product identifiers, such as NUII and UPC, of the drug product, if available.
Marketing Category: ANDA
Product types are broken down into several potential Marketing Categories, such as New Drug Application (NDA), Abbreviated New Drug Application (ANDA), BLA, OTC Monograph, or Unapproved Drug. One and only one Marketing Category may be chosen for a product, not all marketing categories are available to all product types. Currently, only final marketed product categories are included. The complete list of codes and translations can be found at www.fda.gov/edrls under Structured Product Labeling Resources.
Marketing Start Date: 10 Dec, 1986
This is the date that the labeler indicates was the start of its marketing of the drug product.
Marketing End Date: 16 Jan, 2026
This is the date the product will no longer be available on the market. If a product is no longer being manufactured, in most cases, the FDA recommends firms use the expiration date of the last lot produced as the EndMarketingDate, to reflect the potential for drug product to remain available after manufacturing has ceased. Products that are the subject of ongoing manufacturing will not ordinarily have any EndMarketingDate. Products with a value in the EndMarketingDate will be removed from the NDC Directory when the EndMarketingDate is reached.
Application Number: ANDA071297
This corresponds to the NDA, ANDA, or BLA number reported by the labeler for products which have the corresponding Marketing Category designated. If the designated Marketing Category is OTC Monograph Final or OTC Monograph Not Final, then the Application number will be the CFR citation corresponding to the appropriate Monograph (e.g. “part 341”). For unapproved drugs, this field will be null.
Listing Expiration Date: 31 Dec, 2024
This is the date when the listing record will expire if not updated or certified by the firm.

OpenFDA Information:

An openfda section: An annotation with additional product identifiers, such as NUII and UPC, of the drug product, if available.
Manufacturer Name:Mylan Pharmaceuticals Inc.
Name of manufacturer or company that makes this drug product, corresponding to the labeler code segment of the NDC.
RxCUI:856769
856792
The RxNorm Concept Unique Identifier. RxCUI is a unique number that describes a semantic concept about the drug product, including its ingredients, strength, and dose forms.
Original Packager:Yes
Whether or not the drug has been repackaged for distribution.
NUI:N0000175694
M0002356
Unique identifier applied to a drug concept within the National Drug File Reference Terminology (NDF-RT).
UNII:26LUD4JO9K
6RZ6XEZ3CR
Unique Ingredient Identifier, which is a non-proprietary, free, unique, unambiguous, non-semantic, alphanumeric identifier based on a substance’s molecular structure and/or descriptive information.
Pharmacologic Class EPC:Benzodiazepine [EPC]
Established pharmacologic class associated with an approved indication of an active moiety (generic drug) that the FDA has determined to be scientifically valid and clinically meaningful. Takes the form of the pharmacologic class, followed by `[EPC]` (such as `Thiazide Diuretic [EPC]` or `Tumor Necrosis Factor Blocker [EPC]`.
Pharmacologic Class CS:Benzodiazepines [CS]
Chemical structure classification of the drug product’s pharmacologic class. Takes the form of the classification, followed by `[Chemical/Ingredient]` (such as `Thiazides [Chemical/Ingredient]` or `Antibodies, Monoclonal [Chemical/Ingredient].
Pharmacologic Class:Benzodiazepine [EPC]
Benzodiazepines [CS]
Tricyclic Antidepressant [EPC]
These are the reported pharmacological class categories corresponding to the SubstanceNames listed above.
DEA Schedule:CIV
This is the assigned DEA Schedule number as reported by the labeler. Values are CI, CII, CIII, CIV, and CV.

Packaging Information:

Package NDCDescriptionMarketing Start DateMarketing End DateSample Available
0378-0211-01100 TABLET, FILM COATED in 1 BOTTLE, PLASTIC (0378-0211-01)10 Dec, 1986N/ANo
0378-0211-05500 TABLET, FILM COATED in 1 BOTTLE, PLASTIC (0378-0211-05)10 Dec, 1986N/ANo
Package NDC number, known as the NDC, identifies the labeler, product, and trade package size. The first segment, the labeler code, is assigned by the FDA. Description tells the size and type of packaging in sentence form. Multilevel packages will have the descriptions concatenated together.

Product Elements:

Chlordiazepoxide and amitriptyline hydrochloride chlordiazepoxide and amitriptyline hydrochloride chlordiazepoxide chlordiazepoxide amitriptyline hydrochloride amitriptyline silicon dioxide croscarmellose sodium hydroxypropyl cellulose, unspecified hypromellose, unspecified magnesium stearate microcrystalline cellulose polyethylene glycol, unspecified starch, corn sodium lauryl sulfate titanium dioxide fd&c yellow no. 6 d&c yellow no. 10 aluminum lake fd&c blue no. 1--aluminum lake mylan;211 chlordiazepoxide and amitriptyline hydrochloride chlordiazepoxide and amitriptyline hydrochloride chlordiazepoxide chlordiazepoxide amitriptyline hydrochloride amitriptyline silicon dioxide croscarmellose sodium hydroxypropyl cellulose, unspecified hypromellose, unspecified magnesium stearate microcrystalline cellulose polyethylene glycol, unspecified starch, corn sodium lauryl sulfate titanium dioxide calcium sulfate, unspecified form talc mylan;277

Boxed Warning:

Warning: risks from concomitant use with opioids; abuse, misuse, and addiction; dependence and withdrawal reactions; and suicidal thoughts and behaviors • 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 (see warnings and precautions ). • the use of benzodiazepines, including chlordiazepoxide and amitriptyline hydrochloride tablets, 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 chlordiazepoxide and amitriptyline hydrochloride tablets and throughout treatment, assess each patient’s risk for abuse, misuse, and addiction (see warnings ). • the continued use of benzodiazepines, including chlordiazepoxide and amitriptyline hydrochloride tablets, 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 chlordiazepoxide and amitriptyline hydrochloride tablets 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 chlordiazepoxide and amitriptyline hydrochloride tablets or reduce the dosage (see dosage and administration and warnings ). • antidepressants increased the risk of suicidal thoughts and behaviors in pediatric and young adult patients in short-term studies. closely monitor all antidepressant-treated patients for clinical worsening, and for emergence of suicidal thoughts and behaviors (see warnings ). chlordiazepoxide and amitriptyline hydrochloride tablets are not approved for use in pediatric patients (see precautions ).

Indications and Usage:

Indications and usage chlordiazepoxide and amitriptyline hydrochloride tablets are 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 occurs 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.

Warnings:

Warnings risks from concomitant use with opioids concomitant use of benzodiazepines, including chlordiazepoxide and amitriptyline hydrochloride tablets, and opioids may result in profound sedation, respiratory depression, coma, and death. because of these risks, reserve concomitant prescribing of these drugs in patients for whom alternative treatment options are inadequate. observational studies have demonstrated that concomitant use of opioid analgesics and benzodiazepines increases the risk of drug-related mortality compared to use of opioids alone. if a decision is made to prescribe chlordiazepoxide and amitriptyline hydrochloride tablets concomitantly with opioids, prescribe the lowest effective dosages and minimum durations of concomitant use, and follow patients closely for signs and symptoms of respiratory depression and sedation. in patients already receiving an opioid analgesic, prescribe a lower initial dose of chlordiazepoxide and amitriptyline hydrochloride tablets than ind
icated in the absence of an opioid and titrate based on clinical response. if an opioid is initiated in a patient already taking chlordiazepoxide and amitriptyline hydrochloride tablets, prescribe a lower initial dose of the opioid and titrate based upon clinical response. 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 (see precautions: drug-drug interactions ). abuse, misuse, and addiction the use of benzodiazepines, including chlordiazepoxide and amitriptyline hydrochloride tablets, exposes users to the risks of abuse, misuse, and addiction, which can lead to overdose or death. 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 (see drug abuse and dependence: abuse ). before prescribing chlordiazepoxide and amitriptyline hydrochloride tablets and throughout treatment, assess each patient’s risk for abuse, misuse, and addiction (e.g., using a standardized screening tool). use of chlordiazepoxide and amitriptyline hydrochloride tablets, particularly in patients at elevated risk, necessitates counseling about the risks and proper use of chlordiazepoxide and amitriptyline hydrochloride tablets along with monitoring for signs and symptoms of abuse, misuse, and addiction. prescribe the lowest effective dosage; avoid or minimize concomitant use of cns depressants and other substances associated with abuse, misuse, and addiction (e.g., opioid analgesics, stimulants); and advise patients on the proper disposal of unused drug. if a substance use disorder is suspected, evaluate the patient and institute (or refer them for) early treatment, as appropriate. dependence and withdrawal reactions to reduce the risk of withdrawal reactions, use a gradual taper to discontinue chlordiazepoxide and amitriptyline hydrochloride tablets or reduce the dosage (a patient-specific plan should be used to taper the dose) (see dosage and administration: discontinuation or dosage reduction of chlordiazepoxide and amitriptyline hydrochloride tablets ). patients at an increased risk of withdrawal adverse reactions after benzodiazepine discontinuation or rapid dosage reduction include those who take higher dosages, and those who have had longer durations of use. acute withdrawal reactions the continued use of benzodiazepines, including chlordiazepoxide and amitriptyline hydrochloride tablets, may lead to clinically significant physical dependence. abrupt discontinuation or rapid dosage reduction of chlordiazepoxide and amitriptyline hydrochloride tablets after continued use, or administration of flumazenil (a benzodiazepine antagonist) may precipitate acute withdrawal reactions, which can be life-threatening (e.g., seizures) (see drug abuse and dependence: dependence ). protracted withdrawal syndrome in some cases, benzodiazepine users have developed a protracted withdrawal syndrome with withdrawal symptoms lasting weeks to more than 12 months (see drug abuse and dependence: dependence ). suicidal thoughts and behaviors in adolescent and young adults in pooled analyses of placebo-controlled trials of antidepressant drugs (ssris and other antidepressant classes) that included approximately 77,000 adult patients and 4,500 pediatric patients, the incidence of suicidal thoughts and behaviors in antidepressant-treated patients age 24 years and younger was greater than in placebo-treated patients. there was considerable variation in risk of suicidal thoughts and behaviors among drugs, but there was an increased risk identified in young patients for most drugs studied. there were differences in absolute risk of suicidal thoughts and behaviors across the different indications, with the highest incidence in patients with mdd. the drug-placebo differences in the number of cases of suicidal thoughts and behaviors per 1,000 patients treated are provided in table 1. table 1: risk differences of the number of patients of suicidal thoughts and behavior in the pooled placebo-controlled trials of antidepressants in pediatric and adult patients age range drug-placebo difference in number of patients of suicidal thoughts or behaviors per 1,000 patients treated increases compared to placebo < 18 years old 14 additional patients 18 to 24 years old 5 additional patients decreases compared to placebo 25 to 64 years old 1 fewer patient ≥ 65 years old 6 fewer patients it is unknown whether the risk of suicidal thoughts and behaviors in children, adolescents, and young adults extends to longer-term use, i.e., beyond four months. however, there is substantial evidence from placebo-controlled maintenance trials in adults with mdd that antidepressants delay the recurrence of depression and that depression itself is a risk factor for suicidal thoughts and behaviors. monitor all antidepressant-treated patients for any indication for clinical worsening and emergence of suicidal thoughts and behaviors, especially during the initial few months of drug therapy, and at times of dosage changes. counsel family members or caregivers of patients to monitor for changes in behavior and to alert the healthcare provider. consider changing the therapeutic regimen, including possibly discontinuing chlordiazepoxide and amitriptyline hydrochloride tablets, in patients whose depression is persistently worse, or who are experiencing emergent suicidal thoughts or behaviors. activation of mania or hypomania in patients with bipolar disorder, treating a depressive episode with chlordiazepoxide and amitriptyline hydrochloride tablets or another antidepressant may precipitate a mixed/manic episode. prior to initiating treatment with chlordiazepoxide and amitriptyline hydrochloride tablets, screen patients for any personal or family history of bipolar disorder, mania, or hypomania. 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. general 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. in patients with glaucoma, even average doses may precipitate an attack. severe constipation may occur in patients taking tricyclic antidepressants in combination with anticholinergic-type drugs. 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. myocardial infarction and stroke have been reported in patients receiving drugs of this class. because of the sedative effects of chlordiazepoxide and amitriptyline hydrochloride tablets, patients should be cautioned about combined effects with alcohol or other cns depressants. the additive effects may produce a harmful level of sedation and cns depression. patients receiving chlordiazepoxide and amitriptyline hydrochloride tablets should be cautioned against engaging in hazardous occupations requiring complete mental alertness, such as operating machinery or driving a motor vehicle. neonatal sedation and withdrawal syndrome use of chlordiazepoxide and amitriptyline hydrochloride tablets late in pregnancy can result in sedation (respiratory depression, lethargy, hypotonia) and/or withdrawal symptoms (hyperreflexia, irritability, restlessness, tremors, inconsolable crying, and feeding difficulties) in the neonate (see precautions: pregnancy ). monitor neonates exposed to chlordiazepoxide and amitriptyline hydrochloride tablets during pregnancy or labor for signs of sedation and monitor neonates exposed to chlordiazepoxide and amitriptyline hydrochloride tablets during pregnancy for signs of withdrawal; manage these neonates accordingly.

General Precautions:

General 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. in patients with glaucoma, even average doses may precipitate an attack. severe constipation may occur in patients taking tricyclic antidepressants in combination with anticholinergic-type drugs. 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. myocardial infarction and stroke have been reported in patients receiving drugs of this class. because of the sedative effects of chlordiazepoxide and amitriptyline hydrochloride tablets, patients should be cautioned about combined effects with alcohol or other cns depressants. the additive effects may produce a harmful level of sedation and cns depression. patients receiving chlo
rdiazepoxide and amitriptyline hydrochloride tablets should be cautioned against engaging in hazardous occupations requiring complete mental alertness, such as operating machinery or driving a motor vehicle.

General use with caution in patients with a history of seizures. close supervision is required when chlordiazepoxide and amitriptyline hydrochloride tablets are given to hyperthyroid patients or those on thyroid medication. the usual precautions should be observed when treating patients with impaired renal or hepatic function. patients with suicidal ideation should not have easy access to large quantities of the drug. the possibility of suicide in depressed patients remains until significant remission occurs.

Dosage and Administration:

Dosage and administration 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. chlordiazepoxide and amitriptyline hydrochloride tablets 10 mg/25 mg 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. chlordiazepoxide and amitriptyline hydrochloride tablets 5 mg/12.5 mg 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 chlordiazepoxide and amitript
yline hydrochloride tablets prior to initiating treatment with chlordiazepoxide and amitriptyline hydrochloride tablets or another antidepressant, screen patients for a personal or family history of bipolar disorder, mania, or hypomania (see warnings: activation of mania or hypomania ). discontinuation or dosage reduction of chlordiazepoxide and amitriptyline hydrochloride tablets to reduce the risk of withdrawal reactions, use a gradual taper to discontinue chlordiazepoxide and amitriptyline hydrochloride tablets 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 (see warnings: dependence and withdrawal reactions and drug abuse and dependence: dependence ).

Contraindications:

Contraindications chlordiazepoxide and amitriptyline hydrochloride tablets are contraindicated in patients with hypersensitivity to either benzodiazepines or tricyclic antidepressants. it 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. chlordiazepoxide and amitriptyline hydrochloride tablets should then be initiated cautiously with gradual increase in dosage until optimum response is achieved. this drug is contraindicated during the acute recovery phase following myocardial infarction.

Adverse Reactions:

Adverse reactions adverse reactions to chlordiazepoxide and amitriptyline hydrochloride are those associated with the use of either component alone. most frequently reported were drowsiness, dry mouth, constipation, blurred vision, dizziness and bloating. other side effects occurring less commonly included vivid dreams, impotence, tremor, confusion and nasal congestion. many symptoms common to the depressive state, such as anorexia, fatigue, weakness, restlessness and lethargy, have been reported as side effects of treatment with both chlordiazepoxide and amitriptyline hydrochloride tablets and amitriptyline. 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. note included in the listing which follows are adverse reaction
s which have not been reported with chlordiazepoxide and amitriptyline hydrochloride. however, they are included because they have been reported during therapy with one or both of the components or closely related drugs. cardiovascular: hypotension, hypertension, tachycardia, palpitations, myocardial infarction, arrhythmias, heart block, stroke. psychiatric: euphoria, apprehension, poor concentration, delusions, hallucinations, hypomania and increased or decreased libido. neurologic: incoordination, ataxia, numbness, tingling and paresthesias of the extremities, extrapyramidal symptoms, syncope, changes in eeg patterns. anticholinergic: disturbance of accommodation, paralytic ileus, urinary retention, dilatation of urinary tract. allergic: skin rash, urticaria, photosensitization, edema of face and tongue, pruritus. hematologic: bone marrow depression including agranulocytosis, eosinophilia, purpura, thrombocytopenia. gastrointestinal: nausea, epigastric distress, vomiting, anorexia, stomatitis, peculiar taste, diarrhea, black tongue. endocrine: testicular swelling and gynecomastia in the male, breast enlargement, galactorrhea and minor menstrual irregularities in the female, elevation and lowering of blood sugar levels, and syndrome of inappropriate adh (antidiuretic hormone) secretion. other: headache, weight gain or loss, increased perspiration, urinary frequency, mydriasis, jaundice, alopecia, parotid swelling.

Use in Pregnancy:

Pregnancy advise pregnant females that use of chlordiazepoxide and amitriptyline hydrochloride tablets late in pregnancy can result in sedation (respiratory depression, lethargy, hypotonia) and/or withdrawal symptoms (hyperreflexia, irritability, restlessness, tremors, inconsolable crying, and feeding difficulties) in newborns (see warnings: neonatal sedation and withdrawal syndrome and precautions, pregnancy ). instruct patients to inform their healthcare provider if they are pregnant. advise patients that there is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to chlordiazepoxide and amitriptyline hydrochloride tablets during pregnancy (see precautions: pregnancy ).

Pregnancy pregnancy exposure registry there is a pregnancy registry that monitors pregnancy outcomes in women exposed to psychiatric medications, including chlordiazepoxide and amitriptyline hydrochloride tablets, during pregnancy. healthcare providers are encouraged to register patients by calling the national pregnancy registry for psychiatric medications at 1-866-961-2388 or visiting online at https://womensmentalhealth.org/pregnancyregistry/.

Pediatric Use:

Pediatric use safety and effectiveness in the pediatric population have not been established (see box warning and warnings: suicidal thoughts and behaviors in adolescents and young adults ). anyone considering the use of chlordiazepoxide and amitriptyline hydrochloride tablets in a child or adolescent must balance the potential risks with the clinical need.

Geriatric Use:

Geriatric use in elderly and debilitated patients it is recommended that dosage be limited to the smallest effective amount to preclude the development of ataxia, oversedation, confusion or anticholinergic effects. of the total number of subjects in clinical studies of chlordiazepoxide and amitriptyline hydrochloride tablets, 74 individuals were 65 years and older. an additional 34 subjects were between 60 and 69 years of age. no overall differences in safety and effectiveness were observed between these subjects and younger subjects, and other reported clinical experience has not identified differences in responses between the elderly and younger patients, but greater sensitivity of some older individuals cannot be ruled out. the active ingredients in chlordiazepoxide and amitriptyline hydrochloride tablets are known to be substantially excreted by the kidney and the risk of toxic reactions to this drug may be greater in patients with impaired renal function. because elderly patients are more likely to have decreased renal function, care should be taken in dose selection and it may be useful to monitor renal function. sedating drugs may cause confusion and over-sedation in the elderly; elderly patients generally should be started on low doses of chlordiazepoxide and amitriptyline hydrochloride tablets and observed closely. clinical studies of chlordiazepoxide and amitriptyline hydrochloride tablets did not include sufficient numbers of subjects aged 65 years and older to determine whether they respond differently than younger subjects. other reported clinical experience has not identified differences in responses between the elderly and younger patients. in general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal or cardiac function and of concomitant disease or other drug therapy.

Overdosage:

Overdosage overdosage of chlordiazepoxide and amitriptyline hydrochloride tablets, which contain a benzodiazepine (chlordiazepoxide) and a tricyclic antidepressant (amitriptyline hydrochloride), may manifest signs and symptoms related to either of its components. deaths may occur from overdosage with this class of drugs. multiple drug ingestion (including alcohol) is common in deliberate tricyclic antidepressant overdose. signs and symptoms of toxicity develop rapidly after tricyclic antidepressant overdose. critical manifestations of tricyclic antidepressant overdosage include cardiac dysrhythmias, severe hypotension, convulsions and cns depression, including coma. changes in the electrocardiogram, particularly in qrs axis or width, are clinically significant indicators of tricyclic antidepressant toxicity. obtain an ecg and immediately initiate cardiac monitoring; hospital monitoring is required as soon as possible. other signs of overdosage may include confusion, disturbed concentration, transient visual hallucinations, dilated pupils, agitation, hyperactive reflexes, stupor, drowsiness, muscle rigidity, vomiting, hypothermia, hyperpyrexia or any of the symptoms listed under adverse reactions. overdosage of benzodiazepines is characterized by central nervous system depression ranging from drowsiness to coma. in mild to moderate cases, symptoms can include drowsiness, confusion, dysarthria, lethargy, hypnotic state, diminished reflexes, ataxia, and hypotonia. rarely, paradoxical or disinhibitory reactions (including agitation, irritability, impulsivity, violent behavior, confusion, restlessness, excitement, and talkativeness) may occur. in severe overdosage cases, patients may develop respiratory depression and coma. overdosage of benzodiazepines in combination with other cns depressants (including alcohol and opioids) may be fatal (see warnings: abuse, misuse, and addiction ). markedly abnormal (lowered or elevated) blood pressure, heart rate, or respiratory rate raise the concern that additional drugs and/or alcohol are involved in the overdosage. in managing benzodiazepine overdosage, employ general supportive measures, including intravenous fluids and airway management. flumazenil, a specific benzodiazepine receptor antagonist indicated for the complete or partial reversal of the sedative effects of benzodiazepines in the management of benzodiazepine overdosage, can lead to withdrawal and adverse reactions, including seizures with chlordiazepoxide and amitriptyline hydrochloride tablets because overdosage with amitriptyline and other tricyclic and tetracyclic antidepressants increases the risk of seizures. seizure risk is also increased in patients with long-term benzodiazepine use and physical dependency. the risk of withdrawal seizures with flumazenil use also may be increased in patients with epilepsy. flumazenil is contraindicated in patients who have received a benzodiazepine for control of a potentially life-threatening condition (e.g., status epilepticus). contact the poison help line (1-800-222-1222) or medical toxicologist for additional overdosage management recommendations.

dependence:

Dependence physical dependence chlordiazepoxide and amitriptyline hydrochloride tablets 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 (see warnings: dependence and withdrawal reactions ). to reduce the risk of withdrawal reactions, use a gradual taper to discontinue chlordiazepoxide and amitriptyline hydrochloride tablets or reduce the dosage (see dosage and administration: discontinuation or dosage reduction of chlordiazepoxide and amitriptyline hydrochloride tablets and warnings: dependence and withdrawal reactions ). 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.

Description:

Description chlordiazepoxide and amitriptyline hydrochloride tablets, usp combine for oral administration, chlordiazepoxide, an agent for the relief of anxiety and tension, and amitriptyline, an antidepressant. chlordiazepoxide, usp is a benzodiazepine with the formula 7-chloro-2-(methylamino)-5-phenyl-3 h -1,4-benzodiazepine-4-oxide. it is a yellow crystalline powder and is insoluble in water. the chemical structure is: amitriptyline hydrochloride, usp is a dibenzocycloheptadiene derivative. the formula is 10,11-dihydro- n,n -dimethyl-5 h -dibenzo[a,d]cycloheptene-d 5 ,g-propylamine hydrochloride. it is a white or practically white crystalline powder that is freely soluble in water. the chemical structure is: each film-coated tablet for oral administration contains 5 mg of chlordiazepoxide and 14 mg of amitriptyline hydrochloride equivalent to 12.5 mg of amitriptyline or 10 mg of chlordiazepoxide and 27.98 mg of amitriptyline hydrochloride equivalent to 25 mg of amitriptyline. each tablet contains the following inactive ingredients: colloidal silicon dioxide, croscarmellose sodium, hydroxypropyl cellulose, hypromellose, magnesium stearate, microcrystalline cellulose, polyethylene glycol, pregelatinized starch (corn), sodium lauryl sulfate and titanium dioxide. in addition, the 5 mg/12.5 mg tablets also contain d&c yellow no. 10 aluminum lake, fd&c blue no. 1 aluminum lake and fd&c yellow no. 6 aluminum lake and the 10 mg/25 mg tablets also contain calcium sulfate and talc. chlordiazepoxide structural formula amitriptyline hydrochloride structural formula

Clinical Pharmacology:

Clinical pharmacology both components of chlordiazepoxide and amitriptyline hydrochloride tablets exert their action in the central nervous system. extensive studies with chlordiazepoxide in many animal species suggest action in the limbic system. recent evidence indicates that the limbic system is involved in emotional response. taming action was observed in some species. the mechanism of action of amitriptyline in man is not known, but the drug appears to interfere with the reuptake of norepinephrine into adrenergic nerve endings. this action may prolong the sympathetic activity of biogenic amines.

How Supplied:

How supplied chlordiazepoxide and amitriptyline hydrochloride tablets, usp are available containing 5 mg of chlordiazepoxide, usp and 14 mg of amitriptyline hydrochloride, usp equivalent to 12.5 mg of amitriptyline or 10 mg of chlordiazepoxide, usp and 27.98 mg of amitriptyline hydrochloride, usp equivalent to 25 mg of amitriptyline. the 5 mg/12.5 mg tablets are green, film-coated, round, unscored tablets debossed with mylan on one side of the tablet and 211 on the other side. they are available as follows: ndc 0378-0211-01 bottles of 100 tablets ndc 0378-0211-05 bottles of 500 tablets the 10 mg/25 mg tablets are white, film-coated, round, unscored tablets debossed with mylan on one side of the tablet and 277 on the other side. they are available as follows: ndc 0378-0277-01 bottles of 100 tablets ndc 0378-0277-05 bottles of 500 tablets store at 20° to 25°c (68° to 77°f). [see usp controlled room temperature.] store in a dry place. dispense in a tight, light-resistant conta
iner as defined in the usp using a child-resistant closure. pharmacist: dispense a medication guide with each prescription.

Information for Patients:

Information for patients advise the patient to read the fda-approved patient labeling ( medication guide ).

Package Label Principal Display Panel:

Principal display panel – 5 mg/12.5 mg ndc 0378-0211-01 chlordiazepoxide and amitriptyline hcl tablets, usp civ 5 mg/ 12.5 mg* rx only 100 tablets *each film-coated tablet contains 5 mg of chlordiazepoxide, usp and 14 mg of amitriptyline hydrochloride, usp equivalent to 12.5 mg of amitriptyline. dispense in a tight, light-resistant container as defined in the usp using a child-resistant closure. keep container tightly closed. keep this and all medication out of the reach of children. store at 20° to 25°c (68° to 77°f). [see usp controlled room temperature.] store in a dry place. usual dosage: see accompanying prescribing information. pharmacist: dispense the accompanying medication guide to each patient. manufactured for: mylan pharmaceuticals inc. morgantown, wv 26505 u.s.a. made in australia 3448/0 ralp0211a chlordiazepoxide and amitriptyline hydrochloride tablets, usp 5 mg/12.5 mg bottle label

Principal display panel – 10 mg/25 mg ndc 0378-0277-01 chlordiazepoxide and amitriptyline hcl tablets, usp civ 10 mg/ 25 mg* rx only 100 tablets *each film-coated tablet contains 10 mg of chlordiazepoxide, usp and 27.98 mg of amitriptyline hydrochloride, usp equivalent to 25 mg of amitriptyline. dispense in a tight, light-resistant container as defined in the usp using a child-resistant closure. keep container tightly closed. keep this and all medication out of the reach of children. store at 20° to 25°c (68° to 77°f). [see usp controlled room temperature.] store in a dry place. usual dosage: see accompanying prescribing information. pharmacist: dispense the accompanying medication guide to each patient. manufactured for: mylan pharmaceuticals inc. morgantown, wv 26505 u.s.a. made in australia 3450/0 ralp0277a chlordiazepoxide and amitriptyline hydrochloride tablets, usp 10 mg/25 mg bottle label


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