Drug Facts
Composition & Profile
Identifiers & Packaging
16 HOW SUPPLIED/STORAGE AND HANDLING Doxepin HydrochlorideCapsules, USP 50 mg: Ivory opaque cap and ivory opaque body, capsule imprinting on back: A 342 NDC: 70518-4282-00 PACKAGING: 30 in 1 BLISTER PACK Store at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature]. Protect from light. Repackaged and Distributed By: Remedy Repack, Inc. 625 Kolter Dr. Suite #4 Indiana, PA 1-724-465-8762; DRUG: DOXEPIN HYDROCHLORIDE GENERIC: DOXEPIN HYDROCHLORIDE DOSAGE: CAPSULE ADMINSTRATION: ORAL NDC: 70518-4282-0 COLOR: white SHAPE: CAPSULE SCORE: No score SIZE: 16 mm IMPRINT: A342 PACKAGING: 30 in 1 BLISTER PACK ACTIVE INGREDIENT(S): DOXEPIN HYDROCHLORIDE 50mg in 1 INACTIVE INGREDIENT(S): MICROCRYSTALLINE CELLULOSE SODIUM LAURYL SULFATE STARCH, CORN SILICON DIOXIDE MAGNESIUM STEARATE TITANIUM DIOXIDE FERRIC OXIDE YELLOW GELATIN, UNSPECIFIED SHELLAC FERROSOFERRIC OXIDE POTASSIUM HYDROXIDE Remedy_Label
- 16 HOW SUPPLIED/STORAGE AND HANDLING Doxepin HydrochlorideCapsules, USP 50 mg: Ivory opaque cap and ivory opaque body, capsule imprinting on back: A 342 NDC: 70518-4282-00 PACKAGING: 30 in 1 BLISTER PACK Store at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature]. Protect from light. Repackaged and Distributed By: Remedy Repack, Inc. 625 Kolter Dr. Suite #4 Indiana, PA 1-724-465-8762
- DRUG: DOXEPIN HYDROCHLORIDE GENERIC: DOXEPIN HYDROCHLORIDE DOSAGE: CAPSULE ADMINSTRATION: ORAL NDC: 70518-4282-0 COLOR: white SHAPE: CAPSULE SCORE: No score SIZE: 16 mm IMPRINT: A342 PACKAGING: 30 in 1 BLISTER PACK ACTIVE INGREDIENT(S): DOXEPIN HYDROCHLORIDE 50mg in 1 INACTIVE INGREDIENT(S): MICROCRYSTALLINE CELLULOSE SODIUM LAURYL SULFATE STARCH, CORN SILICON DIOXIDE MAGNESIUM STEARATE TITANIUM DIOXIDE FERRIC OXIDE YELLOW GELATIN, UNSPECIFIED SHELLAC FERROSOFERRIC OXIDE POTASSIUM HYDROXIDE Remedy_Label
Overview
Doxepin is a tricyclic antidepressant. The molecular formula of doxepin hydrochloride, USP is C 19 H 21 NO•HCl with a molecular weight of 315.84. It is a white or almost white crystalline powder. It is freely soluble in water, in alcohol and in methylene chloride. Doxepin is a dibenzoxepin derivative. Specifically, it is an isomeric mixture of: 1-Propanamine, 3-dibenz[ b , e ]oxepin-11(6 H )ylidene- N , N -dimethyl-, hydrochloride. The structural formula of doxepin is shown below. Doxepin Hydrochloride Doxepin hydrochloride capsules, USP are for oral administration. Active ingredients for the capsules include: 10 mg, 25, mg, 50 mg, 75 mg and 100 mg of doxepin (equivalent to 11.31 mg, 28.26 mg, 56.53 mg, 84.79 mg and 113.05 mg of doxepin hydrochloride, respectively). Capsule inactive ingredients: colloidal silicon dioxide, magnesium stearate, microcrystalline cellulose, pregelatinized starch and sodium lauryl sulfate. The capsule shell contains gelatin, iron oxide yellow, sodium lauryl sulfate and titanium dioxide. Additionally, 75 mg and 100 mg capsule shell also contains FD&C Blue 1. The capsule shells are printed with edible black ink containing iron oxide black, potassium hydroxide and shellac. FDA approved dissolution method differs from the USP dissolution method. structure
Indications & Usage
Doxepin hydrochloride capsule is indicated for the treatment of major depressive disorder (MDD) in adults. Doxepin hydrochloride capsule is a tricyclic antidepressant (TCA) indicated for the treatment of major depressive disorder (MDD) in adults ( 1 ).
Dosage & Administration
Prior to initiating treatment with doxepin hydrochloride capsules, screen patients for a personal or family history of bipolar disorder, mania, or hypomania. ( 2.1 ) Recommended starting oral dosage is 25 mg three times daily or 75 mg once daily. ( 2.2 ) Recommended target total dosage range is between 75 mg/day and 150 mg/day (may be given once daily or in divided doses). ( 2.2 ) Maximum recommended dosage is 100 mg three times daily. ( 2.2 ) Wait at least 14 days after discontinuation of a monoamine oxidase inhibitor (MAOI) before initiating therapy with doxepin hydrochloride capsules. ( 2.3 ) 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 , 2.5 , 2.6 ). When discontinuing doxepin hydrochloride capsules, gradually reduce the dosage until discontinued. ( 2.7 ) 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)]. 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. 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)]. 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)]. 2.7 Discontinuation of Doxepin Hydrochloride Capsules Treatment When discontinuing doxepin hydrochloride capsules, gradually reduce the dosage until discontinued [see Adverse Reactions (6)].
Warnings & Precautions
Suicidal Thoughts and Behaviors : Monitor for clinical worsening and suicide thoughts and behaviors. Consider changing the therapeutic regimen, including possibly discontinuing doxepin hydrochloride, in patients who are experiencing emergent suicidal thoughts or behaviors. ( 5.1 ) Serotonin Syndrome : Risk increases with concomitant use of other serotonergic drugs. Monitor all patients taking doxepin hydrochloride for the emergence of serotonin syndrome. Discontinue doxepin hydrochloride and any concomitant serotonergic agents immediately and initiate supportive treatment if serotonin syndrome occurs. ( 5.2 , 7 ) Angle-Closure Glaucoma : Avoid use of doxepin hydrochloride in patients with untreated anatomically narrow angles. ( 5.3 ) Sedation and Driving Risks : Because doxepin hydrochloride can cause sedation, warn patients against driving a car or operating dangerous machinery while taking doxepin hydrochloride. ( 5.4 ) Activation of Mania or Hypomania : Prior to initiating antidepressant therapy, screen for bipolar disorder. Doxepin hydrochloride is not approved for use in treating bipolar depression. ( 5.5 ) 5.1 Suicidal Thoughts and Behaviors in Adolescents and Young Adults In pooled analyses of placebo-controlled trials of antidepressant drugs including tricyclic antidepressants and other antidepressant classes that included approximately 77,000 adult patients and 4,500 pediatric patients (doxepin hydrochloride is not approved for use in pediatric patients), the incidence of suicidal thoughts and behaviors in antidepressant-treated patients age 24 years and younger was greater than in placebo-treated patients. There was considerable variation in risk of suicidal thoughts and behaviors among drugs, but there was an increased risk identified in young patients for most drugs studied. The drug-placebo differences in the number of cases of suicidal thoughts and behaviors per 1,000 patients treated are provided in Table 1. Table 1: Risk Differences of the Number of Patients of Suicidal Thoughts and Behaviors in the Pooled Placebo-Controlled Trials of Antidepressants in Pediatric and Adult Patients Age Range Drug-Placebo Difference in Number of Patients of Suicidal Thoughts or Behaviors per 1,000 Patients Treated < 18 years old 14 additional patients 18 to 24 years old 5 additional patients Decreases Compared to Placebo 25 to 64 years old 1 fewer patient ≥ 65 years old 6 fewer patients It is unknown whether the risk of suicidal thoughts and behaviors in pediatric and young adults extends to longer-term use, i.e., beyond four months. However, there is substantial evidence from placebo-controlled maintenance trials in adults with MDD that antidepressants delay the recurrence of depression. Monitor all doxepin hydrochloride-treated patients for clinical worsening and emergence of suicidal thoughts and behaviors, especially during the initial few months of doxepin hydrochloride therapy, and at times of dosage changes. Counsel family members or caregivers of patients to monitor for changes in behavior and to alert the health care provider. Consider changing the therapeutic regimen, including possibly discontinuing doxepin hydrochloride, in patients who are experiencing emergent suicidal thoughts or behaviors. 5.2 Serotonin Syndrome Tricyclic antidepressants, including doxepin hydrochloride, can precipitate serotonin syndrome, a potentially life-threatening condition. This risk is increased with concomitant use of other serotonergic drugs (e.g., other tricyclic antidepressants, SSRIs, serotonin norepinephrine reuptake inhibitors, triptans, tetracyclic antidepressants, opioids), lithium, tryptophan, buspirone, and St. John’s Wort) and with drugs that impair metabolism of serotonin (e.g., MAOIs intended to treat psychiatric disorders and others, such as linezolid or intravenous methylene blue) [see Drug Interactions (7)] . Serotonin syndrome symptoms may include mental status changes (e.g., confusion, agitation, hallucinations, delirium, and coma), autonomic instability (e.g., tachycardia, labile blood pressure, hyperthermia, diaphoresis, and flushing), neuromuscular abnormalities (e.g., tremor, rigidity, clonus, and hyperreflexia), seizures and gastrointestinal signs and symptoms (e.g., nausea, vomiting, diarrhea). Patients should be monitored for the emergence of serotonin syndrome. The concomitant use of doxepin hydrochloride with MAOIs is contraindicated. The use of doxepin hydrochloride within 14 days of discontinuing treatment with an MAOI intended to treat psychiatric disorders is contraindicated. Starting doxepin hydrochloride in a patient who is being treated with an MAOI such as linezolid or intravenous methylene blue is contraindicated. No reports involved the administration of methylene blue by other routes (such as oral or local tissue injection). If it is necessary to initiate treatment with a MAOI such as linezolid or intravenous methylene blue in a patient taking doxepin hydrochloride, discontinue doxepin hydrochloride before initiating treatment with the MAOI [see Dosage and Administration (2.4) and Drug Interactions (7.1)] . Monitor all patients taking doxepin hydrochloride for the emergence of serotonin syndrome. Discontinue doxepin hydrochloride treatment and any concomitant serotonergic agents immediately if the above symptoms occur, and initiate supportive symptomatic treatment. If concomitant use of doxepin hydrochloride with other serotonergic drugs (besides MAOIs which are contraindicated) is clinically warranted, inform patients of the increased risk for serotonin syndrome and monitor for symptoms. 5.3 Angle-Closure Glaucoma The pupillary dilation that occurs following use of many antidepressant drugs including doxepin hydrochloride may trigger an angle closure glaucoma attack in a patient with anatomically narrow angles who does not have a patent iridectomy. 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. Doxepin hydrochloride is contraindicated in patients with glaucoma. Avoid use of doxepin hydrochloride in patients with untreated anatomically narrow angles. 5.4 Sedation and Driving Risks Because doxepin hydrochloride can cause sedation, warn patients of the risk of sedation and caution patients against driving a car or operating dangerous machinery while taking doxepin hydrochloride. Also caution patients that their response to alcohol may be potentiated. Sedating drugs, including doxepin hydrochloride, may cause oversedation in geriatric patients. 5.5 Activation of Mania or Hypomania In patients with bipolar disorder, treating MDD with doxepin hydrochloride may precipitate a mixed/manic episode. Prior to initiating treatment with doxepin hydrochloride, screen patients for any personal or family history of bipolar disorder, mania, or hypomania. doxepin hydrochloride is not approved for use in treating bipolar depression. 5.6 Risk of Seizures Caution should be used when doxepin hydrochloride is given to patients with a history of seizure disorder, because this drug may lower the seizure threshold. Patients with a history of seizures should be monitored during doxepin hydrochloride use to identify recurrence of seizures or increase in frequency of seizures. 5.7 Psychosis In patients with schizophrenia, treatment with doxepin hydrochloride for MDD may activate psychosis. If this occurs, stop doxepin hydrochloride and consider alternative treatment options.
Boxed Warning
SUICIDAL THOUGHTS AND BEHAVIORS Antidepressants increase the risk of suicidal thoughts and behavior in pediatric and young adult patients in short-term studies. Closely monitor all antidepressant-treated patients for clinical worsening and emergence of suicidal thoughts and behaviors [see Warnings and Precautions (5.1)]. Doxepin hydrochloride capsule is not approved for use in pediatric patients [see Use in Specific Populations (8.4)]. WARNING: SUICIDAL THOUGHTS AND BEHAVIORS See full prescribing information for complete boxed warning. Increased risk of suicidal thoughts and behaviors in pediatric and young adults taking antidepressants. Closely monitor all antidepressant-treated patients for clinical worsening and emergence of suicidal thoughts and behaviors ( 5.1 ) Doxepin hydrochloride capsule is not approved for use in pediatric patients ( 8.4 )
Contraindications
Doxepin hydrochloride capsules are contraindicated in patients: With hypersensitivity to doxepin (hypersensitivity reactions have included tongue edema and urticaria). The possibility of cross sensitivity with other dibenzoxepines should be kept in mind. With glaucoma [see Warnings and Precautions (5.3)]. With current or past urinary retention [see Adverse Reactions (6.1)]. Taking MAOIs, or within 14 days of stopping MAOIs (including the MAOIs linezolid or intravenous methylene blue) because of an increased risk of serotonin syndrome [see Warnings and Precautions (5.2) and Drug Interactions (7)]. Hypersensitivity to doxepin ( 4 ) Glaucoma ( 4 ) Current or past urinary retention ( 4 ) Taking MAOIs, or within 14 days of stopping MAOIs ( 4 )
Adverse Reactions
The following clinically significant adverse reactions are described elsewhere in the labeling: Suicidal Thoughts and Behaviors in Adolescents and Young Adults [see Warnings and Precautions (5.1)] Serotonin Syndrome [see Warnings and Precautions (5.2)] Angle-Closure Glaucoma [see Warnings and Precautions (5.3)] Sedation and Driving Risks [see Warnings and Precautions (5.4)] Activation of Mania or Hypomania [see Warnings and Precautions (5.5)] Risk of Seizures [see Warnings and Precautions (5.6)] Psychosis [see Warnings and Precautions (5.7)] Most common adverse reactions (incidence ≥ 5%) are somnolence, dry mouth, dizziness, constipation and fatigue. ( 6.1 ). To report SUSPECTED ADVERSE REACTIONS, contact Alembic Pharmaceuticals Limited at 1-866-210-9797 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch. 6.1 Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice. Adverse reactions (≥ 2% of doxepin hydrochloride-treated patients) in 1,635 doxepin hydrochloride-treated patients with MDD in clinical trials included somnolence (17%), dry mouth (15%), dizziness (6%), constipation (5%), fatigue (5%), blurred vision (3%), tachycardia (3%), hypotension (3%), insomnia (2%), tremor (2%), nausea (2%), hyperhidrosis (2%), and increased weight (2%). Other Adverse Reactions Observed in Clinical Trials Other adverse reactions that occurred at an incidence of < 2% in patients treated with doxepin hydrochloride in clinical trials were: Ear and Labyrinth Disorders : Tinnitus. Gastrointestinal Disorders : Diarrhea, dyspepsia, vomiting. General Disorders and Administration Site Conditions : Asthenia, edema, chills. Metabolism and Nutrition Disorders : Decreased appetite. Nervous System Disorders : Ataxia, paresthesia, headache, extrapyramidal disorder. Psychiatric Disorders : Agitation, confusional state, libido decreased. Pulmonary Disorders : Asthma exacerbation. Renal and Urinary Disorders : Urinary retention. Reproductive System and Breast Disorders : Breast enlargement. Skin & Subcutaneous Tissue Disorders : Rash, pruritus. Vascular Disorders : Flushing. 6.2 Postmarketing Experience The following adverse reactions have been identified during post-approval use of doxepin hydrochloride. Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure. Blood and Lymphatic System Disorders : Agranulocytosis, leukopenia, thrombocytopenia, eosinophilia, purpura. Cardiac Disorders : Conduction disorder, arrhythmia. Endocrine Disorders : Inappropriate antidiuretic hormone secretion. Eye Disorders : Angle-closure glaucoma, mydriasis. Gastrointestinal Disorders : Aphthous stomatitis, abdominal pain upper. General Disorders and Administration Site Conditions : Facial edema, hyperpyrexia. Hepatobiliary Disorders : Jaundice. Investigations : Blood glucose increased. Nervous System Disorders : Hypoesthesia, dysgeusia, convulsion, tardive dyskinesia, serotonin syndrome. Psychiatric Disorders : Hallucination, disorientation. Reproductive System and Breast Disorders : Testicular swelling, gynecomastia, galactorrhea. Skin and Subcutaneous Tissue Disorders : Photosensitivity reaction, tongue edema, alopecia, urticaria. Vascular Disorders : Hypertension. Withdrawal syndrome occurred after stopping doxepin hydrochloride [see Drug Abuse and Dependence (9.3)]. The following adverse reaction has been reported with use with other tricyclic antidepressants: decreased blood glucose.
Drug Interactions
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 within 14 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 See www.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 )
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