Doxepin

Table 2 describe the clinically significant drug interactions of doxepin hydrochloride with other drugs or classes. Table 2: Clinically Significant Drug Interactions with doxepin hydrochloride Monoamine Oxidase Inhibitors Prevention or Management Doxepin Hydrochloride is contraindicated in patients taking monoamine oxidase inhibitors (MAOIs), including MAOIs such as linezolid or intravenous methylene blue. The use of doxepin hydrochloride within14 days of discontinuation of an MAOI or the use of MAOI within 14 days of discontinuation of doxepin hydrochloride is contraindicated. Starting doxepin hydrochloride in a patient who is being treated with an MAOI is contraindicated .

Clinical Effect(s) Concomitant use of doxepin hydrochloride and MAOIs increases the risk of serotonin syndrome [Warnings and Precautions (5.2) ] . Other Serotonergic Drugs (Besides MAOIs) Prevention or Management Monitor patients for signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increases. If serotonin syndrome occurs, consider discontinuation of doxepin hydrochloride and/or concomitant serotonergic drugs [see Warnings and Precautions (5.2) ]. Mechanism and Clinical Effect(s) Concomitant use of doxepin hydrochloride with other serotonergic drugs increases the risk of serotonin syndrome [see Warnings and Precautions (5.2) ].

Strong CYP2D6 Inhibitors Prevention or Management Monitor doxepin plasma concentrations and reduce the doxepin hydrochloride dosage or the strong CYP2D6 inhibitor as appropriate [see Dosage and Administration (2.5) ]. Mechanism and Clinical Effect(s) Concomitant use of doxepin hydrochloride with strong CYP2D6 inhibitors may increase the exposures of doxepin [see Clinical Pharmacology ( 12.3) ] which may increase the risk of doxepin hydrochloride related adverse reactions [see Warnings and Precautions (5) and Adverse Reactions (6)]. Examples Seewww.fda.gov/CYPandTransporterInteractingDrugs for examples of strong CYP2D6 Inhibitors.

Carbamazepine Prevention or Management Monitor doxepin plasma concentrations and consider increasing the doxepin hydrochloride dosage in patients taking carbamazepine. Mechanism and Clinical Effect(s) Concomitant use of carbamazepine with doxepin hydrochloride decreases the exposure of doxepin [see Clinical Pharmacology (12.3) ] which could lead to reduced treatment effect. Cimetidine Prevention or Management Monitor doxepin plasma concentrations and consider reducing the doxepin hydrochloride dosage in patients taking cimetidine.

Mechanism and Clinical Effect(s) Concomitant use of doxepin hydrochloride with cimetidine may increase the exposures of doxepin [see Clinical Pharmacology (12.3) ] which may increase the risk of doxepin hydrochloride-related anticholinergic effects (e.g., dry mouth, blurred vision, constipation) [see Adverse Reactions (6.1) ]. Alcohol Prevention or Management Avoid concomitant use with alcohol. Mechanism and Clinical Effect(s) Doxepin Hydrochloride may potentiate the sedative effects of alcohol [see Warnings and Precautions (5.4) ] .

CNS Depressants Prevention or Management Dosage reduction of doxepin hydrochloride and/or the CNS depressant may be needed based on clinical response and tolerability. Mechanism and Clinical Effect(s) When concomitantly administered with doxepin hydrochloride, the sedative effects of CNS depressant may be potentiated [see Warnings and Precautions (5.4) ] . Tolazamide Prevention or Management Monitor glucose levels and reduce the doxepin hydrochloride dosage as appropriate. Clinical Effect(s) Doxepin Hydrochloride may cause severe hypoglycemia when concomitantly used with tolazamide.

• Serotonergic Drugs : Monitor patients for signs and symptoms of serotonin syndrome, particularly during treatment initiation and dosage increases. If serotonin syndrome occurs, consider discontinuation of doxepin hydrochloride and/or concomitant serotonergic drugs. ( 5.2 , 7 ) • Strong CYP2D6 Inhibitors: Concomitant use of TCAs with drugs that can inhibit CYP2D6 may require lower dosages for the TCA or the other drug, and monitor TCA plasma levels. ( 7 ) • Carbamazepine : Monitor doxepin plasma concentrations and increase doxepin hydrochloride dosage in patients taking carbamazepine.

( 7 ) • Cimetidine : Monitor doxepin plasma concentrations and consider reducing the doxepin hydrochloride dosage in patients taking cimetidine. ( 7 ) • Alcohol: Avoid concomitant use. ( 7 ) • CNS Depressants : Dosage reduction may be needed based on clinical response and tolerability. ( 7 ) • Tolazamide : Monitor glucose levels and reduce the doxepin hydrochloride dosage as appropriate. ( 7 )

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-researchprograms/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…

8.4 Pediatric Use The safety and effectiveness of doxepin hydrochloride in pediatric patients have not been established. Antidepressants increase the risk of suicidal thoughts and behaviors in pediatric patients [see Warnings and Precautions (5.1) ].