Doxepin (oral)

Doxepin (oral)
Black Box Warning
Adult Indications & Dosage
Pediatric Indications & Dosage
Contraindications
Warnings & Precautions
Adverse Reactions
Drug Interactions
Use in Specific Populations
Administration & Monitoring
Overdosage
Pharmacology
Clinical Studies
How Supplied
Images
Patient Counseling Information
Precautions with Alcohol
Brand Names
Look-Alike Names

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Pratik Bahekar, MBBS [2]

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Black Box Warning

Suicidality and Antidepressant Drugs See full prescribing information for complete Boxed Warning. 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 oral solution 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 oral solution is not approved for use in pediatric patients.

Overview

Doxepin (oral) is a Tricyclic antidepressant that is FDA approved for the {{{indicationType}}} of alcoholism - anxiety - depression, anxiety - depression, anxiety - depression - psychoneurotic personality disorder, insomnia, pruritus. There is a Black Box Warning for this drug as shown here. Common adverse reactions include constipation, nausea, xerostomia, dizziness, somnolence, urinary retention, upper respiratory infection.

Adult Indications and Dosage

FDA-Labeled Indications and Dosage (Adult)

Alcoholism - Anxiety - Depression

• Very mild, 25 to 50 mg/day orally initially, gradually increase as needed (max, 300 mg/day).

Alcoholism - Anxiety - Depression

• Mild to moderate, 75 mg ORALLY per day in single or divided doses, increase as needed; usual range is 75 to 150 mg/day (max, 300 mg/day).

Anxiety - Depression

• Very mild, 25 to 50 mg/day ORALLY initially, gradually increase as needed (max, 300 mg/day)
• 75 mg ORALLY per day in single or divided doses, increase as needed; usual range is 75 to 150 mg/day (max, 300 mg/day).

Anxiety - Depression - Psychoneurotic personality disorder

• Outpatients: 75 mg/day ORALLY (divided into 1 to 3 doses); may increase up to a MAX of 150 mg/day
• Inpatients: 150 mg/day ORALLY (divided into 1 to 3 doses); may increase up to a MAX of 300 mg/day

Insomnia

• Less than 65: 6 mg ORALLY once daily; take within 30 minutes of bedtime
• 65 years and older initial dose, 3 mg ORALLY once daily; may increase to 6 mg once daily; take within 30 minutes of bedtime

Pruritus

• Atopic dermatitis or lichen simplex chronicus: 10 mg ORALLY at bedtime; may gradually increase to 25 mg ORALLY at bedtime.
• Atopic dermatitis or lichen simplex chronicus: apply a thin film TOPICALLY to skin 4 times a day (3-4 hr between applications) for a MAX of 8 days.
• Very mild, 25 to 50 mg/day ORALLY initially, gradually increase as needed (max, 300 mg/day
• Mild to moderate, 75 mg ORALLY per day in single or divided doses, increase as needed; usual range is 75 to 150 mg/day (max, 300 mg/day).

Off-Label Use and Dosage (Adult)

Guideline-Supported Use

There is limited information about Off-Label Guideline-Supported Use of Doxepin in adult patients.

Non–Guideline-Supported Use

Urticaria

• 10 to 30 milligrams daily.

• There is limited information about Off-Label Non–Guideline-Supported Use of Doxepin in adult patients.

Pediatric Indications and Dosage

FDA-Labeled Indications and Dosage (Pediatric)

There is limited information regarding Doxepin (oral) FDA-Labeled Indications and Dosage (Pediatric) in the drug label.

Off-Label Use and Dosage (Pediatric)

Guideline-Supported Use

There is limited information about Off-Label Guideline-Supported Use of Doxepin in pediatric patients.

Non–Guideline-Supported Use

There is limited information about Off-Label Non–Guideline-Supported Use of Doxepin in pediatric patients.

Contraindications

• Hypersensitivity

• Doxepin hydrochloride oral solution is contraindicated in individuals who have shown hypersensitivity to the drug. Possibility of cross sensitivity with other dibenzoxepines should be kept in mind.

• Glaucoma or a tendency to urinary retention

• Doxepin hydrochloride oral solution is contraindicated in patients with glaucoma or a tendency to urinary retention. These disorders should be ruled out, particularly in older patients.

Warnings

Suicidality and Antidepressant Drugs See full prescribing information for complete Boxed Warning. 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 oral solution 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 oral solution is not approved for use in pediatric patients.

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.
• 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 oral solution should be written for the smallest quantity 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 oral solution is not approved for use in treating bipolar depression.

Adverse Reactions

Clinical Trials Experience

Central Nervous System

(list/description of adverse reactions)

Cardiovascular

(list/description of adverse reactions)

Respiratory

(list/description of adverse reactions)

Gastrointestinal

(list/description of adverse reactions)

Hypersensitive Reactions

(list/description of adverse reactions)

Miscellaneous

(list/description of adverse reactions)

Postmarketing Experience

Central Nervous System

(list/description of adverse reactions)

Cardiovascular

(list/description of adverse reactions)

Respiratory

(list/description of adverse reactions)

Gastrointestinal

(list/description of adverse reactions)

Hypersensitive Reactions

(list/description of adverse reactions)

Miscellaneous

(list/description of adverse reactions)

Drug Interactions

• (Drug 1)

• (Description)

• (Drug 2)

• (Description)

• (Drug 3)

• (Description)

Use in Specific Populations

Pregnancy

Pregnancy Category (FDA): There is no FDA guidance on usage of Doxepin (oral) in women who are pregnant.
Pregnancy Category (AUS): There is no Australian Drug Evaluation Committee (ADEC) guidance on usage of Doxepin (oral) in women who are pregnant.

Labor and Delivery

There is no FDA guidance on use of Doxepin (oral) during labor and delivery.

Nursing Mothers

There is no FDA guidance on the use of Doxepin (oral) in women who are nursing.

Pediatric Use

There is no FDA guidance on the use of Doxepin (oral) in pediatric settings.

Geriatic Use

There is no FDA guidance on the use of Doxepin (oral) in geriatric settings.

Gender

There is no FDA guidance on the use of Doxepin (oral) with respect to specific gender populations.

Race

There is no FDA guidance on the use of Doxepin (oral) with respect to specific racial populations.

Renal Impairment

There is no FDA guidance on the use of Doxepin (oral) in patients with renal impairment.

Hepatic Impairment

There is no FDA guidance on the use of Doxepin (oral) in patients with hepatic impairment.

Females of Reproductive Potential and Males

There is no FDA guidance on the use of Doxepin (oral) in women of reproductive potentials and males.

Immunocompromised Patients

There is no FDA guidance one the use of Doxepin (oral) in patients who are immunocompromised.

Administration and Monitoring

Administration

There is limited information regarding Doxepin (oral) Administration in the drug label.

Monitoring

There is limited information regarding Doxepin (oral) Monitoring in the drug label.

IV Compatibility

There is limited information regarding the compatibility of Doxepin (oral) and IV administrations.

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 *ADVERSEREACTIONS. Deaths have been reported involving overdose 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 pCO2 < 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.

Pharmacology

There is limited information regarding Doxepin (oral) Pharmacology in the drug label.

Mechanism of Action

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 is virtually devoid of euphoria as a side effect. Characteristic of this type of compound, doxepin has not been demonstrated to produce the physical tolerance or psychological dependence associated with addictive compounds.

Structure

Doxepin hydrochloride is one of a class of psychotherapeutic agents known as dibenzoxepin tricyclic compounds. It is a white crystalline solid readily soluble in water, lower alcohols and chloroform.

Inactive ingredients for the oral concentrate formulation are: glycerin, methylparaben, propylparaben, blueberry-mint flavor, and purified water.

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.

Pharmacodynamics

There is limited information regarding Doxepin (oral) Pharmacodynamics in the drug label.

Pharmacokinetics

There is limited information regarding Doxepin (oral) Pharmacokinetics in the drug label.

Nonclinical Toxicology

There is limited information regarding Doxepin (oral) Nonclinical Toxicology in the drug label.

Clinical Studies

There is limited information regarding Doxepin (oral) Clinical Studies in the drug label.

How Supplied

There is limited information regarding Doxepin (oral) How Supplied in the drug label.

Storage

There is limited information regarding Doxepin (oral) Storage in the drug label.

Images

Drug Images

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Package and Label Display Panel

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Patient Counseling Information

There is limited information regarding Doxepin (oral) Patient Counseling Information in the drug label.

Precautions with Alcohol

Alcohol-Doxepin interaction has not been established. Talk to your doctor about the effects of taking alcohol with this medication.

Brand Names

There is limited information regarding Doxepin (oral) Brand Names in the drug label.

Look-Alike Drug Names

There is limited information regarding Doxepin (oral) Look-Alike Drug Names in the drug label.

Drug Shortage Status

Price

References

The contents of this FDA label are provided by the National Library of Medicine.

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