Doxepin Hydrochloride - Doxepin Hydrochloride capsule

Dosage and Administration (2.4, 2.5, 2.6, 2.7, 2.8)                                        7/2025

Warnings and Precautions (5.2, 5.5)                                                       7/2025

Doxepin hydrochloride capsule is indicated for the treatment of major depressive disorder (MDD) in adults.

• Prior to initiating treatment with doxepin hydrochloride capsules, screen patients for a personal or family history of bipolar disorder, mania, or hypomania. (
  2.1 Screen for Bipolar Disorder Prior to Starting Doxepin Hydrochloride Capsules

  Prior to initiating treatment with doxepin hydrochloride capsules, screen patients for a personal or family history of bipolar disorder, mania, or hypomania

  [see Warnings and Precautions (5.5)].
  )
• Recommended starting oral dosage is 25 mg three times daily or 75 mg once daily. (
  2.2 Recommended Dosage

  The recommended starting oral dosage for doxepin hydrochloride capsule is 25 mg three times daily or 75 mg once daily. The recommended target total oral dosage range for doxepin hydrochloride capsule is between 75 mg/day and 150 mg/day (may be given once daily or in divided doses). The maximum recommended oral dosage for doxepin hydrochloride capsule is 100 mg three times daily.
  )
• Recommended target total dosage range is between 75 mg/day and 150 mg/day (may be given once daily or in divided doses).
• Maximum recommended dosage is 100 mg three times daily.
• Wait at least 14 days after discontinuation of a monoamine oxidase inhibitor (MAOI) before initiating therapy with doxepin hydrochloride capsules. (
  2.3 Switching Patients to or from a Monoamine Oxidase Inhibitor

  Wait at least 14 days after discontinuation of a monoamine oxidase inhibitor (MAOI) before initiating therapy with doxepin hydrochloride capsules

  [see Contraindications (4), Warnings and Precautions (5.2), and Drug Interactions (7)]

  .

  
  
  

  Wait at least 14 days after discontinuation of doxepin hydrochloride capsules before initiating therapy with an MAOI

  [see Contraindications (4.4), Warnings and Precautions (5.2), and Drug Interactions (7)].
  )
• See the Full Prescribing Information for dosage modifications intended to reduce the risk of anticholinergic effects, for strong CYP2D6 inhibitors, and in known CYP2D6 and CYP2C19 poor metabolizers. (
  2.4 Dosage Modifications Intended to Reduce the Risk of Anticholinergic Effects

  If anticholinergic effects (e.g., dry mouth, blurred vision, constipation) develop, reduce the doxepin hydrochloride capsules dosage

  [see Adverse Reactions (6.1)].
  ,
  2.5 Dosage Modifications for Strong CYP2D6 Inhibitors

  Reduce the doxepin hydrochloride capsules dosage based on doxepin plasma concentrations when used concomitantly with strong CYP2D6 inhibitors

  [see Drug Interactions (7)].
  ,
  2.6 Dosage Modifications in Known CYP2D6 and CYP2C19 Poor Metabolizers

  Reduce the doxepin hydrochloride capsules dosage based on doxepin plasma concentrations in patients who are known CYP2D6 and CYP2C19 poor metabolizers

  [see Use in Specific Populations (8.7)].
  ).
• When discontinuing doxepin hydrochloride capsules, gradually reduce the dosage until discontinued. (
  2.7 Discontinuation of Doxepin Hydrochloride Capsules Treatment

  When discontinuing doxepin hydrochloride capsules, gradually reduce the dosage until discontinued

  [see Adverse Reactions (6)].
  )

• 10 mg are buff opaque cap/buff opaque body size ‘4’ hard gelatin capsule shell axially imprinted with ‘A 340’ on cap in black ink and filled with white to off white granular powder.
• 25 mg are ivory opaque cap/white opaque body size ‘3’ hard gelatin capsule shell axially imprinted with ‘A 341’ on cap in black ink and filled with white to off white granular powder.
• 50 mg are ivory opaque cap/ivory opaque body size ‘3’ hard gelatin capsule shell axially imprinted with ‘A 342’ on cap in black ink and filled with white to off white granular powder.
• 75 mg are brite lite green opaque cap/brite lite green opaque body size ‘2’ hard gelatin capsule shell axially imprinted with ‘A 343’ on cap in black ink and filled with white to off white granular powder.
• 100 mg are brite lite green opaque cap/white opaque body size ‘1’ hard gelatin capsule shell axially imprinted with ‘A 344’ on cap in black ink and filled with white to off white granular powder.

Active ingredients in the capsules include: 10 mg, 25, mg, 50 mg, 75 mg and 100 mg of doxepin. 

• Pregnancy
  : Neonates exposed to TCAs, including doxepin hydrochloride, late in the third trimester have developed poor adaptation (respiratory distress, temperature instability, feeding difficulty, hypotonia, irritability). Monitor neonates who were exposed to doxepin hydrochloride in the third trimester of pregnancy for poor neonatal adaptation syndrome. (
  8.1 Pregnancy

  Pregnancy Exposure Registry

  There is a pregnancy exposure registry that monitors pregnancy outcomes in women exposed to antidepressants, including doxepin hydrochloride, during pregnancy. Health care providers are encouraged to advise patients to register by calling the National Pregnancy Registry for Antidepressants 1-866-961-2388 or visiting online at https://womensmentalhealth.org/clinical-and-research programs/pregnancyregistry/antidepressants.

  Risk Summary

  Available data from published epidemiological studies and postmarketing reports have not established an increased risk for major birth defects or miscarriage with doxepin hydrochloride use

  (see Data).

  There are risks

  (see Clinical Considerations)

  :

  
  
  

  • To the mother associated with untreated depression in pregnancy.
  • Poor neonate adaptation from exposure to tricyclic antidepressants (TCAs), including doxepin hydrochloride, during the third trimester of pregnancy
    .

  
  
  

  Animal reproduction toxicity of doxepin has not been fully characterized.

  
  
  

  The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of major birth defect, loss, or other adverse outcomes. In the U.S. general population, the estimated background risk of major birth defects and miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively.

  
  
  

  Clinical Considerations

  
  
  

  Disease-associated Maternal and/or Embryofetal Risk

  Women who discontinue antidepressants during pregnancy are more likely to experience a relapse of MDD than women who continue antidepressants. This finding is from a prospective longitudinal study of 201 pregnant women with a history of MDD who were euthymic and taking antidepressants at the beginning of pregnancy. Consider the risk of untreated MDD when considering discontinuation of doxepin hydrochloride drugs during pregnancy and the postpartum period.

  
  
  

  Fetal/Neonatal Adverse Reactions

  Neonates previously exposed to TCAs, including doxepin hydrochloride, late in the third trimester during pregnancy have developed complications requiring prolonged hospitalization, respiratory support, and tube feeding. Such complications can arise immediately upon delivery. Reported clinical findings have included respiratory distress, cyanosis, apnea, seizures, temperature instability, feeding difficulty, vomiting, hypoglycemia, hypotonia, hypertonia, hyperreflexia, tremor, jitteriness, irritability, and constant crying. These findings are consistent with either direct toxic effects of TCAs or possibly a drug discontinuation syndrome. Monitor neonates who were exposed to doxepin hydrochloride in the third trimester of pregnancy for poor neonatal adaptation syndrome.

  
  
  

  Data

  Human Data:

  Published epidemiological studies of pregnant women exposed to TCAs, including doxepin hydrochloride, have not established an association with major birth defects, miscarriage, or adverse maternal outcomes. Methodological limitations of these observational studies include small sample size and lack of adequate controls.
  )
• Lactation
  : Breastfeeding not recommended. (
  8.2 Lactation

  Risk Summary

  Data from published literature report the presence of doxepin and nordoxepin in human milk. There are reports of excessive sedation, respiratory depression, poor suckling and swallowing and hypotonia in breastfed infants exposed to doxepin at doses used to treat MDD. There are no data on the effects of doxepin on milk production.

  
  
  

  Because of the potential for serious adverse reactions, including excess sedation and respiratory depression in a breastfed infant, advise patients that breastfeeding is not recommended during doxepin hydrochloride treatment.
  )
• Geriatric Use
  : May cause confusion and oversedation. (
  8.5 Geriatric Use

  Clinical studies of doxepin hydrochloride did not include sufficient numbers of patients 65 years of age and older to determine whether they respond differently from younger adult patients.

  
  
  

  Sedating drugs, including doxepin hydrochloride, may cause confusion and oversedation in geriatric patients. The recommended starting doxepin hydrochloride dosage in geriatric patients is generally lower than those of younger adult patients

  .

  
  
  
  )
• CYP2C19 and CYP2D6 Poor Metabolizers
  : Increased risk of doxepin hydrochloride-associated adverse reactions. (
  8.7 Use in Genomic Subgroups

  The recommended doxepin hydrochloride dosage in CYP2C19 and CYP2D6 poor metabolizers is lower than the recommended dosage in CYP2C19 and CYP2D6 normal metabolizers

  [see Dosage and Administration (2.6)].

  
  
  

  According to the literature, doxepin is primarily metabolized by CYP2D6 and/or CYP2C19; thus, the use of doxepin hydrochloride in CYP2D6 and/or CYP2C19 poor metabolizers will likely result in higher doxepin exposures and an increased risk of doxepin hydrochloride-associated adverse reactions.
  )