doxepin 50 mg capsule

Uses

Depressive and Anxiety Disorders

Doxepin shares the pharmacologic actions of the other tricyclic antidepressants and is used principally in the treatment of depression and/or anxiety in psychoneurotic patients, depression and/or anxiety associated with alcoholism or organic disease, and psychotic depressive disorders with associated anxiety, including involutional depression and manic-depressive disorders. Symptoms of psychoneurosis that respond well to doxepin include anxiety, tension, depression, somatic symptoms and concerns, sleep disturbances, guilt, lack of energy, fear, apprehension, and worry.

For further information on treatment of major depression and considerations in choosing the most appropriate antidepressant for a particular patient, including considerations related to patient tolerance, patient age, and cardiovascular, sedative, and suicidality risks, see Considerations in Choosing Antidepressants under Uses: Major Depressive Disorder, in the Tricyclic Antidepressants General Statement 28:16.04.28.

Chronic Idiopathic Urticaria

Doxepin also has been effective in the management of chronic idiopathic urticaria† and may be used as an alternative to antihistamines, which generally are considered as first-line therapy in patients with this condition.

Dosage and Administration

Administration

Doxepin hydrochloride is administered orally. Although doxepin has been administered in up to 3 divided doses throughout the day, it is long-acting and the entire daily dose may be administered at one time. Administration of the entire daily dose at bedtime may reduce daytime sedation.

Each dose of the oral concentrate should be diluted with approximately 120 mL of water, whole or skimmed milk, or orange, grapefruit, tomato, prune, or pineapple juice just prior to administration; the solution is physically incompatible with many carbonated beverages. For patients requiring doxepin therapy while on methadone maintenance, doxepin solution and methadone syrup can be mixed together with Gatorade, lemonade, orange juice, sugar water, Tang, or water, but not with grape juice. Bulk dilution and storage are not recommended by the manufacturers.

Doxepin is applied topically to the skin as an antipruritic. (See Doxepin Hydrochloride 84:08.)

Dosage

Dosage of doxepin hydrochloride is expressed in terms of doxepin. There is a wide range of dosage requirements, and dosage must be carefully individualized. Initial dosages should be low and generally range from 30-150 mg daily, depending on the severity of the condition being treated. Dosage may be gradually adjusted to the level which produces maximal therapeutic effect with minimal toxicity and may range up to 300 mg daily. The manufacturers state that dosages exceeding 300 mg daily rarely produce additional therapeutic benefits. Hospitalized patients under close supervision may generally be given higher dosages than outpatients. Patients with very mild symptomatology or organic brain syndrome should usually be given lower than average dosages and may obtain satisfactory improvement with 25-50 mg of doxepin daily. The manufacturers state that appropriate dosage in geriatric patients should be selected with caution, usually initiating therapy at the low end of the dosage range since decreased hepatic, renal, or cardiac function occurs more frequently in these patients.

When doxepin is administered as a single daily dose, the maximum daily dose recommended by the manufacturers is 150 mg. Commercially available 150-mg capsules of doxepin are intended for maintenance therapy only and are not recommended for initial therapy. Maximum antidepressant effects may not occur for 2 or more weeks after therapy is begun, although anxiolytic effects may develop more rapidly.

After symptoms are controlled, dosage should be gradually reduced to the lowest level which will maintain relief of symptoms. To avoid the possibility of precipitating withdrawal symptoms, doxepin should not be terminated abruptly in patients who have received high dosages for prolonged periods.

Patients should be monitored for possible worsening of depression, suicidality, or unusual changes in behavior, especially at the beginning of therapy or during periods of dosage adjustment. (See Cautions: Precautions and Contraindications, in the Tricyclic Antidepressants General Statement 28:16.04.28.)

Cautions

Doxepin shares the pharmacologic actions and toxic potentials of the tricyclic antidepressants, and the usual precautions of tricyclic antidepressant administration should be observed. Patients should be fully advised about the risks, especially suicidal thinking and behavior (suicidality), associated with tricyclic antidepressant therapy. For a complete discussion,

Pediatric Precautions

Safety of doxepin in children younger than 12 years of age has not been established.

The US Food and Drug Administration (FDA) has determined that antidepressants increase the risk of suicidal thinking and behavior (suicidality) in children and adolescents with major depressive disorder and other psychiatric disorders. However, FDA also states that depression and certain other psychiatric disorders are themselves associated with an increased risk of suicide. Anyone considering the use of doxepin in a child or adolescent for any clinical use must therefore balance the potential risk of therapy with the clinical need. (See Cautions: Precautions and Contraindications and Cautions: Pediatric Precautions, in the Tricyclic Antidepressants General Statement 28:16.04.28.)

Lactation

Lactation

Limited data indicate that doxepin and its active N-demethylated metabolite are distributed into milk. Sedation and serious respiratory depression were reported in a nursing infant whose mother was receiving 75 mg of doxepin daily; substantial concentrations of the active metabolite of the drug were detected in the infant's serum and urine. In addition, poor sucking and swallowing while nursing, drowsiness, muscle hypotonia, and vomiting were reported in a nursing infant whose mother was receiving 35 mg of doxepin daily. Because of the potential for serious adverse reactions to doxepin and/or its active metabolite in nursing infants, a decision should be made whether to discontinue nursing or the drug, taking into account the importance of the drug to the woman.

Pharmacokinetics

Absorption

The pharmacokinetics of doxepin have not been extensively studied, but the drug is well absorbed from the GI tract in animals. Peak plasma concentrations usually occur within 2 hours after oral administration of the drug.

Distribution

Doxepin is highly bound to plasma proteins.

Limited data indicate that doxepin and its active N-demethylated metabolite are distributed into milk in concentrations reportedly ranging from about 30-140% and 10-115%, respectively, of those in maternal serum and that substantial concentrations of the active metabolite have been detected in the serum and urine of nursing infants whose mothers were receiving 75-150 mg of doxepin daily.

Elimination

The plasma half-life of doxepin is 6-24.5 hours. The drug appears to be metabolized via the same pathways as are other tricyclic antidepressants; its N-demethylated metabolite is pharmacologically active.