DOXEPIN HYDROCHLORIDE- doxepin hydrochloride capsule

United States - English - NLM (National Library of Medicine)

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Active ingredient:
DOXEPIN HYDROCHLORIDE (UNII: 3U9A0FE9N5) (DOXEPIN - UNII:5ASJ6HUZ7D)
Available from:
Quality Care Products, LLC
Administration route:
ORAL
Prescription type:
PRESCRIPTION DRUG
Therapeutic indications:
Doxepin hydrochloride capsules are recommended for the treatment of:           1.  Psychoneurotic patients with depression and/or anxiety.           2.  Depression and/or anxiety associated with alcoholism (not to be taken concomitantly with alcohol).           3.  Depression and/or anxiety associated with organic disease (the possibility of drug interaction should be considered if the patient is receiving other drugs concomitantly).           4.  Psychotic depressive disorders with associated anxiety including involutional depression and manic-depressive disorders. The target symptoms of psychoneurosis that respond particularly well to doxepin hydrochloride capsules include anxiety, tension, depression, somatic symptoms and concerns, sleep disturbances, guilt, lack of energy, fear, apprehension and worry. Clinical experience has shown that doxepin hydrochloride capsules are safe and well tolerated even in the elderly patient. Owing to lack of clinical experience in the pediatric population, doxepin h
Product summary:
Doxepin Hydrochloride Capsules, USP are available containing Doxepin Hydrochloride, USP equivalent to 10 mg, 25 mg, 50 mg, 75 mg or 100 mg of Doxepin. Doxepin Hydrochloride Capsules USP, 10 mg are buff colored size “4” hard gelatin capsule filled with white to off-white granules and imprinted with DOX on cap and 10 on body. 55700-783-30 Doxepin Hydrochloride Capsules USP, 25 mg are ivory and white colored size “3” hard gelatin capsule filled with white to off-white granules and imprinted with DOX on cap and 25 on body. Doxepin Hydrochloride Capsules USP, 50 mg are ivory colored size “3” hard gelatin capsule filled with white to off-white granules and imprinted with DOX on cap and 50 on body. Doxepin Hydrochloride Capsules USP, 75 mg are brite lite green colored size “2” hard gelatin capsule filled with white to off-white granules and imprinted with DOX on cap and 75 on body. Doxepin Hydrochloride Capsules USP, 100 mg are brite lite green and white colored size “1” hard gelatin capsule filled with white to off-white granules and imprinted with DOX on cap and 100 on body. Store at 20° to 25°C (68° to 77°F). [See USP Controlled Room Temperature.] Protect from light. Dispense with Medication Guide available at: www.aurobindousa.com/product-medication-guides Distributed by: Aurobindo Pharma USA, Inc. 279 Princeton-Hightstown Road East Windsor, NJ 08520 Manufactured by: Aurobindo Pharma Limited Hyderabad-500 038, India Issued: December 2018
Authorization status:
Abbreviated New Drug Application
Authorization number:
55700-783-30

DOXEPIN HYDROCHLORIDE- doxepin hydrochloride capsule

Quality Care Products, LLC

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Medication Guide

Doxepin Hydrochloride Capsules USP

(dox’ e pin hye” droe klor’ ide)

Antidepressant Medicines, Depression and other Serious Mental Illnesses, and Suicidal Thoughts or Actions

Read the Medication Guide that comes with you or your family member’s antidepressant medicine. This

Medication Guide is only about the risk of suicidal thoughts and actions with antidepressant medicines. Talk

to your, or your family member’s, healthcare provider about:

all risks and benefits of treatment with antidepressant medicines

all treatment choices for depression or other serious mental illness

What is the most important information I should know about antidepressant medicines, depression and other

serious mental illnesses, and suicidal thoughts or actions?

1. Antidepressant medicines may increase suicidal thoughts or actions in some children, teenagers, and young

adults within the first few months of treatment.

2. Depression and other serious mental illnesses are the most important causes of suicidal thoughts and

actions. Some people may have a particularly high risk of having suicidal thoughts or actions. These include

people who have (or have a family history of) bipolar illness (also called manic-depressive illness) or suicidal

thoughts or actions.

3. How can I watch for and try to prevent suicidal thoughts and actions in myself or a family member?

Pay close attention to any changes, especially sudden changes, in mood, behaviors, thoughts, or

feelings. This is very important when an antidepressant medicine is started or when the dose is

changed.

Call the healthcare provider right away to report new or sudden changes in mood, behavior, thoughts,

or feelings.

Keep all follow-up visits with the healthcare provider as scheduled. Call the healthcare provider

between visits as needed, especially if you have concerns about symptoms.

Call a healthcare provider right away if you or your family member has any of the following symptoms,

especially if they are new, worse, or worry you:

thoughts about suicide or dying

attempts to commit suicide

new or worse depression

new or worse anxiety

feeling very agitated or restless

panic attacks

trouble sleeping (insomnia)

new or worse irritability

acting aggressive, being angry, or violent

acting on dangerous impulses

an extreme increase in activity and talking (mania) other unusual changes in behavior or mood

Visual problems: eye pain, changes in vision, swelling or redness in or around the eye

What else do I need to know about antidepressant medicines?

Never stop an antidepressant medicine without first talking to a healthcare provider. Stopping an

antidepressant medicine suddenly can cause other symptoms.

Visual problems: Only some people are at risk for these problems. You may want to undergo an eye

examination to see if you are at risk and receive preventative treatment if you are.

Antidepressants are medicines used to treat depression and other illnesses. It is important to discuss

all the risks of treating depression and also the risks of not treating it. Patients and their families or

other caregivers should discuss all treatment choices with the healthcare provider, not just the use of

antidepressants.

Antidepressant medicines have other side effects. Talk to the healthcare provider about the side

effects of the medicine prescribed for you or your family member.

Antidepressant medicines can interact with other medicines. Know all of the medicines that you or

your family member takes. Keep a list of all medicines to show the healthcare provider. Do not start

new medicines without first checking with your healthcare provider.

Not all antidepressant medicines prescribed for children are FDA approved for use in children. Talk

to your child’s healthcare provider for more information.

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

1088.

This Medication Guide has been approved by the U.S. Food and Drug Administration for all antidepressants.

Dispense with Medication Guide available at: www.aurobindousa.com/product-medication-guides

Distributed by:

Aurobindo Pharma USA, Inc.

279 Princeton-Hightstown Road

East Windsor, NJ 08520

Manufactured by:

Aurobindo Pharma Limited

Hyderabad-500 038, India

Issued: December 2018

Revised: 8/2019

Document Id: 62d96806-bbf8-48f9-8ced-76146d89942f

34391-3

Set id: 9e0e8812-0cf5-46cd-8d88-ce17447e506d

Version: 1

Effective Time: 20190812

Quality Care Products, LLC

DOXEPIN HYDROCHLORIDE- doxepin hydrochloride capsule

Quality Care Products, LLC

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Doxepin Hydrochloride Capsules USP

Rx only

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 doxepin

hydrochloride 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 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. Doxepin hydrochloride is not approved for use in pediatric patients. (See

Warnings: Clinical Worsening and Suicide Risk, Precautions: Information for Patients, and

Precautions: Pediatric Use)

DESCRIPTION

Doxepin hydrochloride is one of a class of psychotherapeutic agents known as dibenzoxepin tricyclic

compounds. The molecular formula of the compound is C

H NOHCl having a molecular weight of

315.84. It is a white or almost white crystalline powder freely soluble in water, in alcohol and in

methylene chloride. Its structural formula is:

Chemically, doxepin hydrochloride is a dibenzoxepin derivative and is the first of a family of tricyclic

psychotherapeutic agents. Specifically, it is an isomeric mixture of: 1-Propanamine, 3-

dibenz[b,e]oxepin-11(6H)ylidene-N,N-dimethyl-, hydrochloride. Each 10 mg, 25 mg, 50 mg, 75 mg and

100 mg of doxepin hydrochloride capsule USP contains doxepin hydrochloride USP is equivalent to 10

mg, 25 mg, 50 mg, 75 mg and 100 mg of doxepin, respectively for oral administration.

Each capsule contains the following inactive ingredients: colloidal silicon dioxide, magnesium stearate,

microcrystalline cellulose, pregelatinized starch (maize) and sodium lauryl sulfate. The empty hard

gelatin capsule shells contain D&C Yellow No. 10, gelatin, sodium lauryl sulfate and titanium dioxide.

In addition, 10 mg, 25 mg and 50 mg contain FD&C Yellow No. 6 and 75 mg and 100 mg contain FD&C

Green No. 3.

The imprinting ink contains black iron oxide, potassium hydroxide, propylene glycol, shellac and strong

ammonia solution.

FDA approved dissolution test specifications differ from USP.

CLINICAL PHARMACOLOGY

The mechanism of action of doxepin hydrochloride is not definitely known. It is not a central nervous

system stimulant nor a monoamine oxidase inhibitor. The current hypothesis is that the clinical effects

are due, at least in part, to influences on the adrenergic activity at the synapses so that deactivation of

norepinephrine by reuptake into the nerve terminals is prevented. Animal studies suggest that doxepin

hydrochloride does not appreciably antagonize the antihypertensive action of guanethidine. In animal

studies anticholinergic, antiserotonin and antihistamine effects on smooth muscle have been

demonstrated. At higher than usual clinical doses, norepinephrine response was potentiated in animals.

This effect was not demonstrated in humans.

At clinical dosages up to 150 mg per day, doxepin hydrochloride can be given to man concomitantly

with guanethidine and related compounds without blocking the antihypertensive effect. At dosages

above 150 mg per day blocking of the antihypertensive effect of these compounds has been reported.

Doxepin hydrochloride is virtually devoid of euphoria as a side effect. Characteristic of this type of

compound, doxepin hydrochloride has not been demonstrated to produce the physical tolerance or

psychological dependence associated with addictive compounds.

INDICATIONS AND USAGE

Doxepin hydrochloride capsules are recommended for the treatment of:

1. Psychoneurotic patients with depression and/or anxiety.

2. Depression and/or anxiety associated with alcoholism (not to be taken concomitantly with

alcohol).

3. Depression and/or anxiety associated with organic disease (the possibility of drug interaction

should be considered if the patient is receiving other drugs concomitantly).

4. Psychotic depressive disorders with associated anxiety including involutional depression and

manic-depressive disorders.

The target symptoms of psychoneurosis that respond particularly well to doxepin hydrochloride

capsules include anxiety, tension, depression, somatic symptoms and concerns, sleep disturbances, guilt,

lack of energy, fear, apprehension and worry.

Clinical experience has shown that doxepin hydrochloride capsules are safe and well tolerated even in

the elderly patient. Owing to lack of clinical experience in the pediatric population, doxepin

hydrochloride capsules are not recommended for use in children under 12 years of age.

CONTRAINDICATIONS

Doxepin hydrochloride capsules are contraindicated in individuals who have shown hypersensitivity to

the drug. Possibility of cross sensitivity with other dibenzoxepines should be kept in mind.

Doxepin hydrochloride capsules are contraindicated in patients with glaucoma or a tendency to urinary

retention. These disorders should be ruled out, particularly in older patients.

WARNINGS

Clinical Worsening and Suicide Risk

Patients with major depressive disorder (MDD), both adult and pediatric, may experience worsening of

their depression and/or the emergence of suicidal ideation and behavior (suicidality) or unusual changes

in behavior, whether or not they are taking antidepressant medications, and this risk may persist until

significant remission occurs. Suicide is a known risk of depression and certain other psychiatric

disorders, and these disorders themselves are the strongest predictors of suicide. There has been a

long-standing concern, however, that antidepressants may have a role in inducing worsening of

depression and the emergence of suicidality in certain patients during the early phases of treatment.

Pooled analyses of short-term placebo-controlled trials of antidepressant drugs (SSRIs and others)

showed that these drugs increase the risk of suicidal thinking and behavior (suicidality) in children,

adolescents, and young adults (ages 18 to 24) with major depressive disorder (MDD) and other

psychiatric disorders. 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 with antidepressants

compared to placebo in adults aged 65 and older.

The pooled analyses of placebo-controlled trials in children and adolescents with MDD, obsessive

compulsive disorder (OCD), or other psychiatric disorders included a total of 24 short-term trials of 9

antidepressant drugs in over 4400 patients. The pooled analyses of placebo-controlled trials in adults

with MDD or other psychiatric disorders included a total of 295 short-term trials (median duration of 2

months) of 11 antidepressant drugs in over 77,000 patients. There was considerable variation in risk of

suicidality among drugs, but a tendency toward an increase in the younger patients for almost all drugs

studied. There were differences in absolute risk of suicidality across the different indications, with the

highest incidence in MDD. The risk differences (drug vs placebo), however, were relatively stable

within age strata and across indications. These risk differences (drug-placebo difference in the number

of cases of suicidality per 1000 patients treated) are provided in Table 1.

Table 1

Age Range

Drug-Placebo Difference in Number of Cases of

Suicidality per 1000 Patients Treated

Increases Compared to Placebo

<18

14 additional cases

18 to 24

5 additional cases

Decreases Compared to Placebo

25 to 64

1 fewer case

≥65

6 fewer cases

No suicides occurred in any of the pediatric trials. There were suicides in the adult trials, but the

number was not sufficient to reach any conclusion about drug effect on suicide.

It is unknown whether the suicidality risk extends to longer-term use, i.e., beyond several months.

However, there is substantial evidence from placebo-controlled maintenance trials in adults with

depression that the use of antidepressants can delay the recurrence of depression.

All patients being treated with antidepressants for any indication should be monitored

appropriately and observed closely for clinical worsening, suicidality, and unusual changes in

behavior, especially during the initial few months of a course of drug therapy, or at times of dose

changes, either increases or decreases.

The following symptoms, anxiety, agitation, panic attacks, insomnia, irritability, hostility,

aggressiveness, impulsivity, akathisia (psychomotor restlessness), hypomania, and mania, have been

reported in adult and pediatric patients being treated with antidepressants for major depressive disorder

as well as for other indications, both psychiatric and nonpsychiatric. Although a causal link between the

emergence of such symptoms and either the worsening of depression and/or the emergence of suicidal

impulses has not been established, there is concern that such symptoms may represent precursors to

emerging suicidality.

Consideration should be given to changing the therapeutic regimen, including possibly discontinuing

the medication, in patients whose depression is persistently worse, or who are experiencing emergent

suicidality or symptoms that might be precursors to worsening depression or suicidality, especially if

these symptoms are severe, abrupt in onset, or were not part of the patient's presenting symptoms.

Families and caregivers of patients being treated with antidepressants for major depressive

disorder or other indications, both psychiatric and nonpsychiatric, should be alerted about the

need to monitor patients for the emergence of agitation, irritability, unusual changes in behavior,

and the other symptoms described above, as well as the emergence of suicidality, and to report

such symptoms immediately to health care providers Such monitoring should include daily

observation by families and caregivers. Prescriptions for doxepin hydrochloride should be written

for the smallest quantity of tablets consistent with good patient management, in order to reduce the risk

of overdose.

Screening Patients for Bipolar Disorder: A major depressive episode may be the initial presentation

of bipolar disorder. It is generally believed (though not established in controlled trials) that treating

such an episode with an antidepressant alone may increase the likelihood of precipitation of a

mixed/manic episode in patients at risk for bipolar disorder. Whether any of the symptoms described

above represent such a conversion is unknown. However, prior to initiating treatment with an

antidepressant, patients with depressive symptoms should be adequately screened to determine if they

are at risk for bipolar disorder; such screening should include a detailed psychiatric history, including a

family history of suicide, bipolar disorder, and depression. It should be noted that doxepin

hydrochloride is not approved for use in treating bipolar depression.

Angle-Closure Glaucoma: The pupillary dilation that occurs following use of many antidepressant

drugs including doxepin hydrochloride may trigger an angle closure attack in a patient with anatomically

narrow angles who does not have a patent iridectomy.

Geriatric Use: The use of doxepin hydrochloride on a once-a-day dosage regimen in geriatric patients

should be adjusted carefully based on the patient’s condition (see PRECAUTIONS−Geriatric Use).

Pregnancy: Reproduction studies have been performed in rats, rabbits, monkeys and dogs and there was

no evidence of harm to the animal fetus. The relevance to humans is not known. Since there is no

experience in pregnant women who have received this drug, safety in pregnancy has not been

established. There has been a report of apnea and drowsiness occurring in a nursing infant whose

mother was taking doxepin hydrochloride.

Pediatric Use: The use of doxepin hydrochloride in children under 12 years of age is not recommended

because safe conditions for its use have not been established.

PRECAUTIONS

Information for Patients

Prescribers or other health professionals should inform patients, their families, and their caregivers

about the benefits and risks associated with treatment with doxepin hydrochloride and should counsel

them in its appropriate use. A patient Medication Guide about “Antidepressant Medicines, Depression

and other Serious Mental Illness, and Suicidal Thoughts or Actions” is available for doxepin

hydrochloride. The prescriber or health professional should instruct patients, their families, and their

caregivers to read the Medication Guide and should assist them in understanding its contents. Patients

should be given the opportunity to discuss the contents of the Medication Guide and to obtain answers

to any questions they may have. The complete text of the Medication Guide is reprinted at the end of this

document.

Patients should be advised of the following issues and asked to alert their prescriber if these occur

while taking doxepin hydrochloride.

Patients should be advised that taking doxepin hydrochloride capsules can cause mild pupillary dilation,

which in susceptible individuals, can lead to an episode of angle-closure glaucoma. Preexisting

glaucoma is almost always open-angle glaucoma because angle-closure glaucoma, when diagnosed, can

be treated definitively with iridectomy. Open-angle glaucoma is not a risk factor for angle closure

glaucoma. Patients may wish to be examined to determine whether they are susceptible to angle closure,

and have a prophylactic procedure (e.g., iridectomy), if they are susceptible.

Clinical Worsening and Suicide Risk: Patients, their families, and their caregivers should be

encouraged to be alert to the emergence of anxiety, agitation, panic attacks, insomnia, irritability,

hostility, aggressiveness, impulsivity, akathisia (psychomotor restlessness), hypomania, mania, other

unusual changes in behavior, worsening of depression, and suicidal ideation, especially early during

antidepressant treatment and when the dose is adjusted up or down. Families and caregivers of patients

should be advised to look for the emergence of such symptoms on a day-to-day basis, since changes

may be abrupt. Such symptoms should be reported to the patient's prescriber or health professional,

especially if they are severe, abrupt in onset, or were not part of the patient's presenting symptoms.

Symptoms such as these may be associated with an increased risk for suicidal thinking and behavior and

indicate a need for very close monitoring and possibly changes in the medication.

Patients should be advised that taking doxepin hydrochloride can cause mild pupillary dilation, which in

susceptible individuals, can lead to an episode of angle closure glaucoma. Pre-existing glaucoma is

almost always open-angle glaucoma because angle closure glaucoma, when diagnosed, can be treated

definitively with iridectomy. Open-angle glaucoma is not a risk factor for angle closure glaucoma.

Patients may wish to be examined to determine whether they are susceptible to angle closure, and have a

prophylactic procedure (e.g., iridectomy), if they are susceptible.

Drug Interactions: 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.,

citalopram, escitalopram, 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 co-administration 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 co-therapy, an increased dose of

tricyclic antidepressant may be required. It is desirable to monitor TCA plasma levels whenever a TCA

is going to be co-administered with another drug known to be an inhibitor of P450 2D6.

Doxepin is primarily metabolized by CYP2D6 (with CYP1A2 & CYP3A4 as minor pathways). Inhibitors

or substrates of CYP2D6 (i.e., quinidine, selective serotonin reuptake inhibitors [SSRIs]) may increase

the plasma concentration of doxepin when administered concomitantly. The extent of interaction depends

on the variability of effect on CYP2D6. The clinical significance of this interaction with doxepin has

not been systematically evaluated.

MAO Inhibitors: Serious side effects and even death have been reported following the concomitant use

of certain drugs with MAO inhibitors. Therefore, MAO inhibitors should be discontinued at least two

weeks prior to the cautious initiation of therapy with doxepin hydrochloride. The exact length of time

may vary and is dependent upon the particular MAO inhibitor being used, the length of time it has been

administered, and the dosage involved.

Cimetidine: Cimetidine has been reported to produce clinically significant fluctuations in steady-state

serum concentrations of various tricyclic antidepressants. Serious anticholinergic symptoms (i.e.,

severe dry mouth, urinary retention and blurred vision) have been associated with elevations in the

serum levels of tricyclic antidepressant when cimetidine therapy is initiated. Additionally, higher than

expected tricyclic antidepressant levels have been observed when they are begun in patients already

taking cimetidine. In patients who have been reported to be well controlled on tricyclic antidepressants

receiving concurrent cimetidine therapy, discontinuation of cimetidine has been reported to decrease

established steady-state serum tricyclic antidepressant levels and compromise their therapeutic effects.

Alcohol: It should be borne in mind that alcohol ingestion may increase the danger inherent in any

intentional or unintentional doxepin hydrochloride overdosage. This is especially important in patients

who may use alcohol excessively.

Tolazamide: A case of severe hypoglycemia has been reported in a type II diabetic patient maintained on

tolazamide (1 gm/day) 11 days after the addition of doxepin (75 mg/day).

Drowsiness: Since drowsiness may occur with the use of this drug, patients should be warned of the

possibility and cautioned against driving a car or operating dangerous machinery while taking the drug.

Patients should also be cautioned that their response to alcohol may be potentiated.

Sedating drugs may cause confusion and oversedation in the elderly; elderly patients generally should

be started on low doses of doxepin hydrochloride and observed closely. (See

PRECAUTIONS−Geriatric Use.)

Suicide: Since suicide is an inherent risk in any depressed patient and may remain so until significant

improvement has occurred, patients should be closely supervised during the early course of therapy.

Prescriptions should be written for the smallest feasible amount.

Psychosis: Should increased symptoms of psychosis or shift to manic symptomatology occur, it may be

necessary to reduce dosage or add a major tranquilizer to the dosage regimen.

Pediatric Use-Safety and effectiveness in the pediatric population have not been established (see BOX

WARNING and WARNINGS—Clinical Worsening and Suicide Risk).

Anyone considering the use of doxepin hydrochloride in a child or adolescent must balance the

potential risks with the clinical need.

Geriatric Use: A determination has not been made whether controlled clinical studies of doxepin

hydrochloride included sufficient numbers of subjects aged 65 and over to define a difference in

response from 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.

The extent of renal excretion of doxepin hydrochloride has not been determined. Because elderly

patients are more likely to have decreased renal function, care should be taken in dose selections.

Sedating drugs may cause confusion and oversedation in the elderly; elderly patients generally should

be started on low doses of doxepin hydrochloride and observed closely. (See WARNINGS.)

ADVERSE REACTIONS

NOTE: Some of the adverse reactions noted below have not been specifically reported with doxepin

hydrochloride use. However, due to the close pharmacological similarities among the tricyclics, the

reactions should be considered when prescribing doxepin hydrochloride.

Anticholinergic Effects: Dry mouth, blurred vision, constipation, and urinary retention have been reported.

If they do not subside with continued therapy, or become severe, it may be necessary to reduce the

dosage.

Central Nervous System Effects: Drowsiness is the most commonly noticed side effect. This tends to

disappear as therapy is continued. Other infrequently reported CNS side effects are confusion,

disorientation, hallucinations, numbness, paresthesias, ataxia, extrapyramidal symptoms, seizures, tardive

dyskinesia, and tremor.

Cardiovascular: Cardiovascular effects including hypotension, hypertension, and tachycardia have been

reported occasionally.

Allergic: Skin rash, edema, photosensitization, and pruritus have occasionally occurred.

Hematologic: Eosinophilia has been reported in a few patients. There have been occasional reports of

bone marrow depression manifesting as agranulocytosis, leukopenia, thrombocytopenia, and purpura.

Gastrointestinal: Nausea, vomiting, indigestion, taste disturbances, diarrhea, anorexia, and aphthous

stomatitis have been reported. (See Anticholinergic Effects.)

Endocrine: Raised or lowered libido, testicular swelling, gynecomastia in males, enlargement of breasts

and galactorrhea in the female, raising or lowering of blood sugar levels, and syndrome of

inappropriate antidiuretic hormone secretion have been reported with tricyclic administration.

Other: Dizziness, tinnitus, weight gain, sweating, chills, fatigue, weakness, flushing, jaundice, alopecia,

headache, exacerbation of asthma, angle closure glaucoma, mydriasis and hyperpyrexia (in association

with chlorpromazine) have been occasionally observed as adverse effects.

Withdrawal Symptoms: The possibility of development of withdrawal symptoms upon abrupt cessation

of treatment after prolonged doxepin hydrochloride administration should be borne in mind. These are

not indicative of addiction and gradual withdrawal of medication should not cause these symptoms.

DOSAGE AND ADMINISTRATION

For most patients with illness of mild to moderate severity, a starting daily dose of 75 mg is

recommended. Dosage may subsequently be increased or decreased at appropriate intervals and

according to individual response. The usual optimum dose range is 75 mg/day to 150 mg/day.

In more severely ill patients higher doses may be required with subsequent gradual increase to 300

mg/day if necessary. Additional therapeutic effect is rarely to be obtained by exceeding a dose of 300

mg/day.

In patients with very mild symptomatology or emotional symptoms accompanying organic disease, lower

doses may suffice. Some of these patients have been controlled on doses as low as 25 to 50 mg/day.

The total daily dosage of doxepin hydrochloride may be given on a divided or once-a-day dosage

schedule. If the once-a-day schedule is employed, the maximum recommended dose is 150 mg/day. This

dose may be given at bedtime. The 150 mg capsule strength is intended for maintenance therapy

only and is not recommended for initiation of treatment.

Anti-anxiety effect is apparent before the antidepressant effect. Optimal antidepressant effect may not be

evident for two to three weeks.

OVERDOSAGE

Deaths may occur from overdosage with this class of drugs. Multiple drug ingestion (including

alcohol) is common in deliberate tricyclic antidepressant overdose. As the management is complex and

changing, it is recommended that the physician contact a poison control center for current information on

treatment. Signs and symptoms of toxicity develop rapidly after tricyclic antidepressant overdose;

therefore, hospital monitoring is required as soon as possible.

Manifestations: Critical manifestations of overdose 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.

Other signs of overdose 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.

Deaths have been reported involving overdoses of doxepin.

General Recommendations:

General: Obtain an ECG and immediately initiate cardiac monitoring. Protect the patient’s airway,

establish an intravenous line and initiate gastric decontamination. A minimum of six hours of observation

with cardiac monitoring and observation for signs of CNS or respiratory depression, hypotension,

cardiac dysrhythmias and/or conduction blocks, and seizures is strongly advised. If signs of toxicity

occur at any time during this period, extended monitoring is recommended. There are case reports of

patients succumbing to fatal dysrhythmias late after overdose; these patients had clinical evidence of

significant poisoning prior to death and most received inadequate gastrointestinal decontamination.

Monitoring of plasma drug levels should not guide management of the patient.

Gastrointestinal Decontamination: All patients suspected of tricyclic antidepressant overdose should

receive gastrointestinal decontamination. This should include large volume gastric lavage followed by

activated charcoal. If consciousness is impaired, the airway should be secured prior to lavage. Emesis

is contraindicated.

Cardiovascular: A maximal limb-lead QRS duration of ≥0.10 seconds may be the best indication of the

severity of the overdose. Intravenous sodium bicarbonate should be used to maintain the serum pH in the

range of 7.45 to 7.55. If the pH response is inadequate, hyperventilation may also be used. Concomitant

use of hyperventilation and sodium bicarbonate should be done with extreme caution, with frequent pH

monitoring. A pH >7.60 or a pCO <20 mm Hg is undesirable. Dysrhythmias unresponsive to sodium

bicarbonate therapy/hyperventilation may respond to lidocaine, bretylium or phenytoin. Type 1A and 1C

antiarrhythmics are generally contraindicated (e.g., quinidine, disopyramide, and procainamide).

In rare instances, hemoperfusion may be beneficial in acute refractory cardiovascular instability in

patients with acute toxicity. However, hemodialysis, peritoneal dialysis, exchange transfusions, and

forced diuresis generally have been reported as ineffective in tricyclic antidepressant poisoning.

CNS: In patients with CNS depression, early intubation is advised because of the potential for abrupt

deterioration. Seizures should be controlled with benzodiazepines, or if these are ineffective, other

anticonvulsants (e.g., phenobarbital, phenytoin). Physostigmine is not recommended except to treat life-

threatening symptoms that have been unresponsive to other therapies, and then only in consultation with a

poison control center.

Psychiatric Follow-up: Since overdosage is often deliberate, patients may attempt suicide by other

means during the recovery phase. Psychiatric referral may be appropriate.

Pediatric Management: The principles of management of child and adult overdosages are similar. It is

strongly recommended that the physician contact the local poison control center for specific pediatric

treatment.

HOW SUPPLIED

Doxepin Hydrochloride Capsules, USP are available containing Doxepin Hydrochloride, USP

equivalent to 10 mg, 25 mg, 50 mg, 75 mg or 100 mg of Doxepin.

Doxepin Hydrochloride Capsules USP, 10 mg are buff colored size “4” hard gelatin capsule filled

with white to off-white granules and imprinted with DOX on cap and 10 on body.

55700-783-30

Doxepin Hydrochloride Capsules USP, 25 mg are ivory and white colored size “3” hard gelatin

capsule filled with white to off-white granules and imprinted with DOX on cap and 25 on body.

Doxepin Hydrochloride Capsules USP, 50 mg are ivory colored size “3” hard gelatin capsule filled

with white to off-white granules and imprinted with DOX on cap and 50 on body.

Doxepin Hydrochloride Capsules USP, 75 mg are brite lite green colored size “2” hard gelatin

capsule filled with white to off-white granules and imprinted with DOX on cap and 75 on body.

Doxepin Hydrochloride Capsules USP, 100 mg are brite lite green and white colored size “1” hard

gelatin capsule filled with white to off-white granules and imprinted with DOX on cap and 100 on body.

Store at 20° to 25°C (68° to 77°F). [See USP Controlled Room Temperature.] Protect from light.

Dispense with Medication Guide available at: www.aurobindousa.com/product-medication-guides

Distributed by:

Aurobindo Pharma USA, Inc.279 Princeton-Hightstown Road

East Windsor, NJ 08520

Manufactured by:

Aurobindo Pharma LimitedHyderabad-500 038, India

Issued: December 2018

Medication Guide

Doxepin Hydrochloride Capsules USP

(dox’ e pin hye” droe klor’ ide)

Antidepressant Medicines, Depression and other Serious Mental Illnesses, and Suicidal

Thoughts or Actions

Read the Medication Guide that comes with you or your family member’s antidepressant medicine. This

Medication Guide is only about the risk of suicidal thoughts and actions with antidepressant medicines.

Talk to your, or your family member’s, healthcare provider about:

all risks and benefits of treatment with antidepressant medicines

all treatment choices for depression or other serious mental illness

What is the most important information I should know about antidepressant medicines,

depression and other serious mental illnesses, and suicidal thoughts or actions?

1. Antidepressant medicines may increase suicidal thoughts or actions in some children,

teenagers, and young adults within the first few months of treatment.

2. Depression and other serious mental illnesses are the most important causes of suicidal

thoughts and actions. Some people may have a particularly high risk of having suicidal thoughts

or actions. These include people who have (or have a family history of) bipolar illness (also called

manic-depressive illness) or suicidal thoughts or actions.

3. How can I watch for and try to prevent suicidal thoughts and actions in myself or a family

member?

Pay close attention to any changes, especially sudden changes, in mood, behaviors, thoughts, or

feelings. This is very important when an antidepressant medicine is started or when the dose is

changed.

Call the healthcare provider right away to report new or sudden changes in mood, behavior,

thoughts, or feelings.

Keep all follow-up visits with the healthcare provider as scheduled. Call the healthcare provider

between visits as needed, especially if you have concerns about symptoms.

Call a healthcare provider right away if you or your family member has any of the following

symptoms, especially if they are new, worse, or worry you:

thoughts about suicide or dying

attempts to commit suicide

new or worse depression

new or worse anxiety

feeling very agitated or restless

panic attacks

trouble sleeping (insomnia)

new or worse irritability

acting aggressive, being angry, or violent

acting on dangerous impulses

an extreme increase in activity and talking (mania) other unusual changes in behavior or mood

Visual problems: eye pain, changes in vision, swelling or redness in or around the eye

What else do I need to know about antidepressant medicines?

Never stop an antidepressant medicine without first talking to a healthcare provider. Stopping

an antidepressant medicine suddenly can cause other symptoms.

Visual problems: Only some people are at risk for these problems. You may want to undergo an eye

examination to see if you are at risk and receive preventative treatment if you are.

Antidepressants are medicines used to treat depression and other illnesses. It is important to

discuss all the risks of treating depression and also the risks of not treating it. Patients and their

families or other caregivers should discuss all treatment choices with the healthcare provider, not

just the use of antidepressants.

Antidepressant medicines have other side effects. Talk to the healthcare provider about the side

effects of the medicine prescribed for you or your family member.

Antidepressant medicines can interact with other medicines. Know all of the medicines that you

or your family member takes. Keep a list of all medicines to show the healthcare provider. Do not

start new medicines without first checking with your healthcare provider.

Not all antidepressant medicines prescribed for children are FDA approved for use in

children. Talk to your child’s healthcare provider for more information.

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

800-FDA-1088.

This Medication Guide has been approved by the U.S. Food and Drug Administration for all

antidepressants.

Dispense with Medication Guide available at: www.aurobindousa.com/product-medication-guides

Distributed by:

Aurobindo Pharma USA, Inc.

279 Princeton-Hightstown Road

East Windsor, NJ 08520

Manufactured by:

Aurobindo Pharma Limited

Hyderabad-500 038, India

Issued: December 2018

DOXEPIN HYDROCHLORIDE

doxepin hydrochloride capsule

Product Information

Product T ype

HUMAN PRESCRIPTION DRUG

Ite m Code (Source )

NDC:5570 0 -78 3(NDC:59 6 51-173)

Route of Administration

ORAL

Active Ingredient/Active Moiety

Ingredient Name

Basis of Strength

Stre ng th

DO XEPIN HYDRO CHLO RIDE (UNII: 3U9 A0 FE9 N5) (DOXEPIN - UNII:5ASJ6 HUZ7D)

DOXEPIN

10 mg

Quality Care Products, LLC

Inactive Ingredients

Ingredient Name

Stre ng th

SILICO N DIO XIDE (UNII: ETJ7Z6 XBU4)

MAGNESIUM STEARATE (UNII: 70 0 9 7M6 I30 )

MICRO CRYSTALLINE CELLULO SE 10 2 (UNII: PNR0 YF6 9 3Y)

STARCH, CO RN (UNII: O8 232NY3SJ)

SO DIUM LAURYL SULFATE (UNII: 36 8 GB5141J)

D&C YELLO W NO . 10 (UNII: 35SW5USQ3G)

FD&C YELLO W NO . 6 (UNII: H77VEI9 3A8 )

GELATIN, UNSPECIFIED (UNII: 2G8 6 QN327L)

TITANIUM DIO XIDE (UNII: 15FIX9 V2JP)

FERRO SO FERRIC O XIDE (UNII: XM0 M8 7F357)

PO TASSIUM HYDRO XIDE (UNII: WZH3C48 M4T)

PRO PYLENE GLYCO L (UNII: 6 DC9 Q16 7V3)

SHELLAC (UNII: 46 N10 7B71O)

AMMO NIA (UNII: 5138 Q19 F1X)

Product Characteristics

Color

WHITE (Buff)

S core

no sco re

S hap e

CAPSULE

S iz e

14mm

Flavor

Imprint Code

DOX;10

Contains

Packag ing

#

Item Code

Package Description

Marketing Start Date

Marketing End Date

1

NDC:5570 0 -78 3-30

10 0 in 1 BOTTLE; Type 0 : No t a Co mbinatio n Pro duct

0 8 /0 9 /20 19

Marketing Information

Marke ting Cate gory

Application Numbe r or Monograph Citation

Marke ting Start Date

Marke ting End Date

ANDA

ANDA2116 0 3

0 8 /0 9 /20 19

Labeler -

Quality Care Products, LLC (831276758)

Establishment

Name

Ad d re s s

ID/FEI

Busine ss Ope rations

Quality Care Pro ducts, LLC

8 31276 758

re pa c k(5570 0 -78 3)

Revised: 8/2019

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