doxepin hydrochloride 3 mg Tablet, 30-count
Other active recalls for Doxepin Hydrochloride (different manufacturers) — 1 · tap to view
🆔 Identity & classification
Where does this data come from?
🏷️ RxNorm drug class
This medicine belongs to the Tricyclic Antidepressant class.
Where does this data come from?
🏭 Manufacturer & labeler
Where does this data come from?
🩺 Clinical
Doxepin is used to treat depression and anxiety. Doxepin is in a class of medications called tricyclic antidepressants. It works by increasing the amounts of certain natural substances in the brain that are needed for mental balance. Doxepin is also available as a tablet to treat insomnia. This monograph only gives information about doxepin for depression or anxiety. If you are using this medication for insomnia, read the monograph entitled doxepin (insomnia).
Read the full MedlinePlus article ↗- Good question — doxepin does have a history as an antidepressant, but what you're being prescribed is a much lower-dose version specifically approved for sleep. It's used for peopl...
- What exactly is doxepin being used for here? I thought it was an antidepressant.
- Yes, timing really does matter. You should take doxepin at least 3 hours after your last meal — especially if that meal was high in fat. Eating close to your dose makes the medicat...
- Does it matter when I take it or if I eat first?
Patient education
Supplement & herbal interactions
Doxepin may be associated with lower levels of 1 nutrient — worth a chat with your pharmacist, not a cause for alarm.
Where does this data come from?
Ask a licensed pharmacist directly — free, answered by our team.
💊 What it looks like
Where does this data come from?
🧪 Inactive Ingredients / Excipients
Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.
💡 Tap an ingredient (hover on desktop) to see what it is and why it’s used.
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UNII H3R47K3TBD
FD&C Blue No. 1 is a synthetic blue dye approved for use in foods and medicines. It serves as a colorant to give the medication its distinctive appearance and help with product identification.
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UNII 70097M6I30
Magnesium stearate is a salt made from magnesium and stearic acid, a fatty substance. It's used in tablets and capsules as a lubricant and glidant to help ingredients flow smoothly during manufacturing and prevent sticking.
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UNII OP1R32D61U
Microcrystalline cellulose is a purified form of cellulose, a natural fiber from plant sources. It acts as a binder and filler in tablets and capsules, helping hold ingredients together and give the medicine its shape and size.
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UNII ETJ7Z6XBU4
Silicon dioxide is a naturally occurring mineral used as a glidant and anti-caking agent. It helps powder ingredients flow smoothly and prevents clumping during manufacturing and storage.
4 inactive ingredients listed in the exact product block matched to this NDC.
Where does this data come from?
ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.Inactive ingredient FAQ
Are inactive ingredients the same for every manufacturer?
Why might an inactive ingredient be missing?
Can inactive ingredients matter?
💲 Pricing
A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.
| Price system | Per ea | Per package |
|---|---|---|
| Retail pharmacies payNADAC · weekly | $7.724 | $231.73 / 30 tablets |
| Medicaid paysCMS SDUD · 12 mo | No recent Medicaid claims on file for this NDC — rare and low-volume NDCs are suppressed in the public data. | |
| Medicare drug plans payPart D · Q2 2026 | $3.87 | $116.24 / 30 tablets |
Where does this data come from?
🔁 Therapeutic equivalents
| Product | Labeler | Pack | NADAC/unit | TE | Status | Price vs. this |
|---|---|---|---|---|---|---|
| Doxepin 3 mg 00228-3315-03 | Actavis | 30 tablets | $1.364 | AB | Availability likely | save 82% |
| Doxepin 3 mg 27241-0280-30 | Ajanta | 30 tablets | $1.364 | AB | Availability likely | save 82% |
| doxepin hydrochloride 3 mg 51672-4246-02 | Sun | 30 tablets | $1.364 | AB | Availability likely | save 82% |
| Doxepin 3 mg 59651-0844-30 | Aurobindo | 30 tablets | $1.364 | AB | Availability likely | save 82% |
| Doxepin 3 mg 64380-0203-01 | Strides | 30 tablets | $1.364 | AB | Availability likely | save 82% |
| Doxepin 3 mg 72603-0222-01 | North | 30 tablets | $1.364 | AB | Availability likely | save 82% |
| Doxepin 3 mg 72819-0161-03 | Archis | 30 tablets | $1.364 | AB | Availability likely | save 82% |
| doxepin hydrochloride 3 mgthis 44183-0103-30 | Currax | 30 tablets | $7.724 | AB | FDA listed | — |
| Doxepin 3 mg 10135-0758-30 | Marlex | 30 tablets | — | AB | FDA listed | — |
| Silenor 3 mg 42847-0103-03 | Currax | 30 tablets | — | AB | FDA listed | — |
| Doxepin hydrochloride 3 mg 51407-0811-30 | Golden | 30 tablets | — | BX | FDA listed | — |
| doxepin 3 mg 70771-1528-00 | Zydus | 1000 tablets | — | AB | FDA listed | — |
| Doxepin 3 mg 72162-2474-03 | Bryant | 30 tablets | — | AB | FDA listed | — |
| Doxepin hydrochloride 3 mg 72205-0052-05 | Novadoz | 500 tablets | — | BX | FDA listed | — |
| doxepin 3 mg 72578-0181-01 | Viona | 100 tablets | — | AB | FDA listed | — |
| doxepin hydrochloride 3 mg 51407-0727-30 | Golden | 30 tablets | — | AB | FDA listed | — |
Where does this data come from?
⏳ Availability & generic status
FDA-approved generic versions are listed, and recent pricing/market data suggests they may be available — see Therapeutic equivalents.
Why the date isn’t exact: Generic timing can change because patents may be challenged, settled, licensed, added, removed, or worked around with a narrower label — and FDA approval does not always mean a pharmacy can get the generic today.
🛈 What do these terms mean?
- Patent
- Legal protection listed in the Orange Book that may delay generic approval or launch. Issued by the U.S. Patent & Trademark Office.
- Substance patent
- Covers the active drug molecule itself — the hardest to design around. A generic generally can’t launch until it expires.
- Formulation (product) patent
- Covers a specific formulation or dosage form. A generic can sometimes work around it with a different formulation.
- Method-of-use patent
- A patent covering one specific approved use of the drug — not necessarily the whole molecule. A generic can sometimes launch with a “skinny label” that carves out the protected use and keeps the others.
- Skinny label
- A generic label that omits a still-patented use when the FDA allows it — letting a generic reach the market for the unprotected uses.
- Exclusivity
- FDA-granted marketing protection, separate from patents — e.g. 5-yr new chemical entity, 7-yr orphan drug, or a +6-month pediatric extension.
- Paragraph IV
- A generic applicant’s formal challenge to a listed patent. It can potentially lead to earlier generic entry, but often involves litigation or a settlement.
- RLD / RS
- Reference Listed Drug — the brand product the FDA uses as the reference for generic applications. Reference Standard — the product the FDA expects generics to compare against in bioequivalence testing.
- TE / AB rating
- FDA therapeutic-equivalence rating. An AB rating generally means the FDA considers a generic therapeutically equivalent to — and substitutable for — the brand.
- LOE (loss of exclusivity)
- The latest patent or exclusivity currently listed — the loss-of-exclusivity / latest-listed-protection date shown on this page. Paragraph-IV challenges and settlements can move the real date earlier; FDA approval and a manufacturer’s decision to market can move it later.
Built from the FDA Orange Book. The bars above are scaled to each protection’s expiry; the red LOE marker is the last one to lapse.
| Patent | Type | Use code | Expires |
|---|---|---|---|
| US 9107898 ↗ | Method of use | U-620 | May 1, 2028 |
| US 9486437 ↗ | Method of use | U-620 | May 18, 2027 |
| US 9861607 ↗ | Method of use | U-620 | May 18, 2027 |
| US 10238620 ↗ | Method of use | U-620 | May 18, 2027 |
| US 7915307 ↗ | Method of use | U-620 | Aug 24, 2027 |
| US 8513299 ↗ | Method of use | U-620 | Sep 7, 2030 |
| US 9572814 ↗ | Method of use | U-620 | Jul 20, 2027 |
| US 9572814 ↗ | Method of use | U-620 | Jul 20, 2027 |
| US 7915307 ↗ | Method of use | U-620 | Aug 24, 2027 |
| US 8513299 ↗ | Method of use | U-620 | Sep 7, 2030 |
| US 12083090 ↗ | Method of use | U-620 | May 18, 2027 |
| US 12083090 ↗ | Method of use | U-620 | May 18, 2027 |
| US 9861607 ↗ | Method of use | U-620 | May 18, 2027 |
| US 9486437 ↗ | Method of use | U-620 | May 18, 2027 |
| US 10238620 ↗ | Method of use | U-620 | May 18, 2027 |
| US 10548871 ↗ | Method of use | U-620 | Apr 11, 2028 |
| US 10548871 ↗ | Method of use | U-620 | Apr 11, 2028 |
| US 10653660 ↗ | Method of use | U-620 | Jul 20, 2027 |
| US 10653662 ↗ | Method of use | U-620 | May 18, 2027 |
| US 10653662 ↗ | Method of use | U-620 | May 18, 2027 |
| US 10653660 ↗ | Method of use | U-620 | Jul 20, 2027 |
| US 11110074 ↗ | Method of use | U-620 | Jul 20, 2027 |
| US 11110074 ↗ | Method of use | U-620 | Jul 20, 2027 |
| US 11096920 ↗ | Method of use | U-620 | Apr 11, 2028 |
| US 11096920 ↗ | Method of use | U-620 | Apr 11, 2028 |
| US 11234954 ↗ | Method of use | U-620 | Jan 18, 2028 |
| US 11234954 ↗ | Method of use | U-620 | Jan 18, 2028 |
| US 9107898 ↗ | Method of use | U-620 | May 1, 2028 |
| US 9907780 ↗ | Drug product | — | Apr 11, 2028 |
| US 9907780 ↗ | Drug product | — | Apr 11, 2028 |
| US 9532971 ↗ | Drug product | — | Jun 1, 2029 |
| US 9532971 ↗ | Drug product | — | Jun 1, 2029 |
Is there a generic version of DOXEPIN HCL 3 MG TABLET?
The FDA approved a generic — why can’t I get it at my pharmacy yet?
Why do different websites show different generic release dates?
What does “FDA listed” mean?
What does a patent or protection date mean here?
What does “current Orange Book estimate” mean?
Can a generic come out before the last patent expires?
Can a generic come out after the listed dates?
What is the difference between patents and exclusivity?
Why are there multiple patent dates?
Where does this data come from?
🔬 Reported adverse events (FAERS)
Top reported reactions
Age at onset
Reporter sex
Serious outcomes
Where does this data come from?
📦 Packaging — all sizes for this product
| Package NDC | Description | Marketing start | Status |
|---|---|---|---|
| 44183-0103-30 You're viewing this | 30 TABLET in 1 BOTTLE (44183-103-30) | 2010-08-01 | Active |
📄 Full prescribing information FDA SPL
🎯 Indications and Usage ▾
1. INDICATIONS AND USAGE Doxepin HCl Tablets is indicated for the treatment of insomnia characterized by difficulty with sleep maintenance. The clinical trials performed in support of efficacy were up to 3 months in duration. Doxepin HCl Tablets are indicated for the treatment of insomnia characterized by difficulties with sleep maintenance. ( 1 , 14 )
⏱️ Dosage and Administration ▾
2. DOSAGE AND ADMINISTRATION The dose of Doxepin HCl Tablets should be individualized. Initial dose: 6 mg, once daily for adults ( 2.1 ) and 3 mg, once daily for the elderly.
( 2.1 , 2.2 ) Take within 30 minutes of bedtime. Total daily dose should not exceed 6 mg. ( 2.3 ) Should not be taken within 3 hours of a meal.
( 2.3 , 12.3 ) 2.1. Dosing in Adults The recommended dose of Doxepin HCl Tablets for adults is 6 mg once daily. A 3 mg once daily dose may be appropriate for some patients, if clinically indicated.
2.2. Dosing in the Elderly The recommended starting dose of Doxepin HCl Tablets in elderly patients (≥ 65 years old) is 3 mg once daily. The daily dose can be increased to 6 mg, if clinically indicated.
2.3. Administration Doxepin HCl Tablets should be taken within 30 minutes of bedtime. To minimize the potential for next day effects, Doxepin HCl Tablets should not be taken within 3 hours of a meal [ see Clinical Pharmacology (12.3) ].
The total Doxepin HCl Tablets dose should not exceed 6 mg per day.
💊 Dosage Forms and Strengths ▾
3. DOSAGE FORMS AND STRENGTHS Doxepin HCl Tablets is an immediate-release, oval-shaped, tablet for oral administration available in strengths of 3 mg and 6 mg. The tablets are blue (3 mg) or green (6 mg) and are debossed with 3 or 6, respectively, on one side and SP on the other. Doxepin HCl Tablets are not scored. 3 mg and 6 mg tablets. Tablets not scored. ( 3 )
⛔ Contraindications ▾
4. CONTRAINDICATIONS Hypersensitivity to doxepin hydrochloride, inactive ingredients, or other dibenzoxepines. ( 4.1 ) Co-administration with Monoamine Oxidase Inhibitors (MAOIs): Do not administer if patient is taking MAOIs or has used MAOIs within the past two weeks.
( 4.2 ) Untreated narrow angle glaucoma or severe urinary retention. ( 4.3 ) 4.1. Hypersensitivity Doxepin HCl Tablets is contraindicated in individuals who have shown hypersensitivity to doxepin HCl, any of its inactive ingredients, or other dibenzoxepines.
4.2. Co-administration with Monoamine Oxidase Inhibitors (MAOIs) Serious side effects and even death have been reported following the concomitant use of certain drugs with MAO inhibitors. Do not administer Doxepin HCl Tablets if patient is currently on MAOIs or has used MAOIs within the past two weeks.
The exact length of time may vary depending on the particular MAOI dosage and duration of treatment. 4.3. Glaucoma and Urinary Retention Doxepin HCl Tablets is contraindicated in individuals with untreated narrow angle glaucoma or severe urinary retention.
⚠️ Warnings and Cautions ▾
5. WARNINGS AND PRECAUTIONS Need to Evaluate for Co-morbid Diagnoses: Reevaluate if insomnia persists after 7 to 10 days of use. ( 5.1 ) Abnormal thinking, behavioral changes, complex behaviors: May include "Sleep-driving" and hallucinations.
Immediately evaluate any new onset behavioral changes. ( 5.2 ) Depression: Worsening of depression or suicidal thinking may occur. Prescribe the least amount feasible to avoid intentional overdose.( 5.3 ) CNS-depressant effects: Use can impair alertness and motor coordination.
Avoid engaging in hazardous activities such as operating a motor vehicle or heavy machinery after taking drug. ( 5.4 ) Do not use with alcohol. ( 5.4 , 7.3 ) Potential additive effects when used in combination with CNS depressants or sedating antihistamines.
Dose reduction may be needed. ( 5.4 , 7.4 ) Patients with severe sleep apnea: Doxepin HCl Tablets is ordinarily not recommended for use in this population. ( 8.7 ) 5.1.
Need to Evaluate for Comorbid Diagnoses Because sleep disturbances may be the presenting manifestation of a physical and/or psychiatric disorder, symptomatic treatment of insomnia should be initiated only after careful evaluation of the patient. The failure of insomnia to remit after 7 to 10 days of treatment may indicate the presence of a primary psychiatric and/or medical illness that should be evaluated. Exacerbation of insomnia or the emergence of new cognitive or behavioral abnormalities may be the consequence of an unrecognized psychiatric or physical disorder.
Such findings have emerged during the course of treatment with hypnotic drugs. 5.2. Abnormal Thinking and Behavioral Changes Complex behaviors such as "sleep-driving" (i.e., driving while not fully awake after ingestion of a hypnotic, with amnesia for the event) have been reported with hypnotics.
These events can occur in hypnotic-naive as well as in hypnotic-experienced persons. Although behaviors such as "sleep-driving" may occur with hypnotics alone at therapeutic doses, the use of alcohol and other CNS depressants with hypnotics appears to increase the risk of such behaviors, as does the use of hypnotics at doses exceeding the maximum recommended dose. Due to the risk to the patient and the community, discontinuation of Doxepin HCl Tablets should be strongly considered for patients who report a "sleep-driving" episode.
Other complex behaviors (e.g., preparing and eating food, making phone calls, or having sex) have been reported in patients who are not fully awake after taking a hypnotic. As with "sleep-driving", patients usually do not remember these events. Amnesia, anxiety and other neuro-psychiatric symptoms may occur unpredictably.
5.3. Suicide Risk and Worsening of Depression In primarily depressed patients, worsening of depression, including suicidal thoughts and actions (including completed suicides), has been reported in association with the use of hypnotics. Doxepin, the active ingredient in Doxepin HCl Tablets, is an antidepressant at doses 10- to 100-fold higher than in Doxepin HCl Tablets.
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. Risk from the lower dose of doxepin in Doxepin HCl Tablets can not be excluded. It can rarely be determined with certainty whether a particular instance of the abnormal behaviors listed above is drug induced, spontaneous in origin, or a result of an underlying psychiatric or physical disorder.
Nonetheless, the emergence of any new behavioral sign or symptom of concern requires careful and immediate evaluation. 5.4. CNS Depressant Effects After taking Doxepin HCl Tablets, patients should confine their activities to those necessary to prepare for bed.
Patients should avoid engaging in hazardous activities, such as operating a motor vehicle or heavy machinery, at night after taking Doxepin HCl Tablets,…
🤒 Adverse Reactions ▾
6. ADVERSE REACTIONS The following serious adverse reactions are discussed in greater detail in other sections of labeling: Abnormal thinking and behavioral changes [see Warnings and Precautions (5.2) ] . Suicide risk and worsening of depression [see Warnings and Precautions (5.3) ] .
CNS Depressant effects [see Warnings and Precautions (5.4) ] . The most common treatment-emergent adverse reactions, reported in ≥ 2% of patients treated with Doxepin HCl Tablets, and more commonly than in patients treated with placebo, were somnolence/sedation, nausea, and upper respiratory tract infection. ( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Macoven at 1-800-793-2145 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .
6.1. Clinical Trials Experience The pre-marketing development program for Doxepin HCl Tablets included doxepin HCl exposures in 1017 subjects (580 insomnia patients and 437 healthy subjects) from 12 studies conducted in the United States. 863 of these subjects (580 insomnia patients and 283 healthy subjects) participated in six randomized, placebo-controlled efficacy studies with Doxepin HCl Tablets doses of 1 mg, 3 mg, and 6 mg for up to 3-months in duration.
Because clinical studies 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. However, data from the Doxepin HCl Tablets studies provide the physician with a basis for estimating the relative contributions of drug and non-drug factors to adverse reaction incidence rates in the populations studied. Associated with Discontinuation of Treatment The percentage of subjects discontinuing Phase 1, 2, and 3 trials for an adverse reaction was 0.6% in the placebo group compared to 0.4%, 1.0%, and 0.7% in the Doxepin HCl Tablets 1 mg, 3 mg, and 6 mg groups, respectively.
No reaction that resulted in discontinuation occurred at a rate greater than 0.5%. Adverse Reactions Observed at an Incidence of ≥ 2% in Controlled Trials Table 1 shows the incidence of treatment-emergent adverse reactions from three long-term (28 to 85 days) placebo-controlled studies of Doxepin HCl Tablets in adult (N = 221) and elderly (N = 494) subjects with chronic insomnia. Reactions reported by Investigators were classified using a modified MedDRA dictionary of preferred terms for purposes of establishing incidence.
The table includes only reactions that occurred in 2% or more of subjects who received Doxepin HCl Tablets 3 mg or 6 mg in which the incidence in subjects treated with Doxepin HCl Tablets was greater than the incidence in placebo-treated subjects. Table 1 Incidence (%) of Treatment-Emergent Adverse Reactions in Long-term Placebo-Controlled Clinical Trials System Organ Class Preferred Term Includes reactions that occurred at a rate of ≥ 2% in any Doxepin HCl Tablets-treated group and at a higher rate than placebo. Placebo (N=278) Doxepin HCl Tablets 3 mg (N=157) Doxepin HCl Tablets 6 mg (N=203) Nervous System Disorders Somnolence/Sedation 4 6 9 Infections and Infestations Upper Respiratory Tract Infection/Nasopharyngitis 2 4 2 Gastroenteritis 0 2 0 Gastrointestinal Disorders Nausea 1 2 2 Vascular Disorders Hypertension 0 3 < 1 The most common treatment-emergent adverse reaction in the placebo and each of the Doxepin HCl Tablets dose groups was somnolence/sedation.
6.2. Studies Pertinent to Safety Concerns for Sleep-promoting Drugs Residual Pharmacological Effect in Insomnia Trials Five randomized, placebo-controlled studies in adults and the elderly assessed next-day psychomotor function within 1 hour of awakening utilizing the digit-symbol substitution test (DSST), symbol copying test (SCT), and visual analog scale (VAS) for sleepiness, following night time administration of Doxepin HCl Tablets. In a one-night, double-blind study conducted in 565 healthy adult subjects experiencing transient insomni…
🔄 Drug Interactions ▾
7. DRUG INTERACTIONS MAO inhibitors: Doxepin HCl Tablets should not be administered in patients on MAOIs within the past two weeks. ( 4.2 ) Cimetidine: Increases exposure to doxepin.
( 7.2 ) Alcohol: Sedative effects may be increased with doxepin. ( 7.3 , 5.4 ) CNS Depressants and Sedating Antihistamines: Sedative effects may be increased with doxepin. ( 7.4 , 5.4 ) Tolazamide: A case of severe hypoglycemia has been reported.
( 7.5 ) 7.1. Cytochrome P450 Isozymes Doxepin HCl Tablets is primarily metabolized by hepatic cytochrome P450 isozymes CYP2C19 and CYP2D6, and to a lesser extent, by CYP1A2 and CYP2C9. Inhibitors of these isozymes may increase the exposure of doxepin.
Doxepin HCl Tablets is not an inhibitor of any CYP isozymes at therapeutically relevant concentrations. The ability of Doxepin HCl Tablets to induce CYP isozymes is not known. 7.2.
Cimetidine Doxepin HCl Tablets exposure is doubled with concomitant administration of cimetidine, a nonspecific inhibitor of CYP isozymes. A maximum dose of 3 mg is recommended in adults and elderly when cimetidine is co-administered with Doxepin HCl Tablets [see Clinical Pharmacology (12.3) ] 7.3. Alcohol When taken with Doxepin HCl Tablets, the sedative effects of alcohol may be potentiated [ see Warnings and Precautions (5.2 , 5.4) ].
7.4. CNS Depressants and Sedating Antihistamines When taken with Doxepin HCl Tablets, the sedative effects of sedating antihistamines and CNS depressants may be potentiated [ see Warnings and Precautions (5.2 , 5.4) ]. 7.5.
Tolazamide A case of severe hypoglycemia has been reported in a type II diabetic patient maintained on tolazamide (1 g/day) 11 days after the addition of oral doxepin (75 mg/day).
👥 Use in Specific Populations ▾
8. USE IN SPECIFIC POPULATIONS Pregnancy: Third trimester use may increase the risk for symptoms of poor adaptation (respiratory distress, temperature instability, feeding difficulties, hypotonia, tremor, irritability) in the neonate. ( 8.1 ) Lactation: Breastfeeding not recommended.
( 8.2 ) Pediatric Use: Safety and effectiveness have not been evaluated. ( 8.4 ) Geriatric Use: The recommended starting dose is 3 mg. Monitor prior to considering dose escalation.
( 2.2 , 8.5 ) Use in Patients with Comorbid Illness: Initiate treatment with 3 mg in patients with hepatic impairment or tendency to urinary retention. ( 8.6 , 4.3 ) 8.1. Pregnancy Risk Summary Available data from published epidemiologic studies and postmarketing reports have not established an increased risk of major birth defects or miscarriage (see Data ) .
There are risks of poor neonatal adaptation with exposure to tricyclic antidepressants (TCAs), including doxepin, during pregnancy (see Clinical Considerations ) . In animal reproduction studies, oral administration of doxepin to rats and rabbits during the period of organogenesis caused adverse developmental effects at doses 65 and 23 times the maximum recommended human dose (MRHD) of 6 mg/day based on AUC, respectively. Oral administration of doxepin to pregnant rats during pregnancy and lactation resulted in decreased pup survival and a delay in pup growth at doses 60 times the MRHD based on AUC (see Data ) .
The estimated 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 Fetal/Neonatal adverse reactions Neonates exposed to TCAs, including doxepin, late in the third trimester 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, 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 HCl Tablets in the third trimester of pregnancy for poor neonatal adaptation syndrome. Data Human Data Published epidemiologic studies of pregnant women exposed to TCAs, including doxepin, 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. Animal Data When doxepin (30, 100, and 150 mg/kg/day) was administered orally to pregnant rats during the period of organogenesis, developmental toxicity (increased incidences of fetal structural abnormalities consisting of non-ossified bones in the skull and sternum and decreased fetal body weights) and maternal toxicity were noted at ≥100 mg/kg/day, which produced plasma exposures (AUCs) of doxepin and nordoxepin (the primary metabolite in humans) approximately 65 and 53 times, respectively, the plasma AUCs at the MRHD.
The plasma exposures at the no-effect dose for embryo-fetal developmental toxicity in rats (30 mg/kg/day) are approximately 6 and 5 times the plasma AUCs for doxepin and nordoxepin, respectively, at the MRHD. When doxepin (10, 30, and 60 mg/kg/day) was administered orally to pregnant rabbits during the period of organogenesis, fetal body weights were reduced at the highest dose in the absence of maternal toxicity, which produced plasma AUCs of doxepin and nordoxepin approximately 23 and 56 times, respectively, the plasma AUCs at the M…
🤰 Pregnancy ▾
8.1. Pregnancy Risk Summary Available data from published epidemiologic studies and postmarketing reports have not established an increased risk of major birth defects or miscarriage (see Data ) . There are risks of poor neonatal adaptation with exposure to tricyclic antidepressants (TCAs), including doxepin, during pregnancy (see Clinical Considerations ) .
In animal reproduction studies, oral administration of doxepin to rats and rabbits during the period of organogenesis caused adverse developmental effects at doses 65 and 23 times the maximum recommended human dose (MRHD) of 6 mg/day based on AUC, respectively. Oral administration of doxepin to pregnant rats during pregnancy and lactation resulted in decreased pup survival and a delay in pup growth at doses 60 times the MRHD based on AUC (see Data ) . The estimated 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 Fetal/Neonatal adverse reactions Neonates exposed to TCAs, including doxepin, late in the third trimester 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, 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 HCl Tablets in the third trimester of pregnancy for poor neonatal adaptation syndrome. Data Human Data Published epidemiologic studies of pregnant women exposed to TCAs, including doxepin, 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.
Animal Data When doxepin (30, 100, and 150 mg/kg/day) was administered orally to pregnant rats during the period of organogenesis, developmental toxicity (increased incidences of fetal structural abnormalities consisting of non-ossified bones in the skull and sternum and decreased fetal body weights) and maternal toxicity were noted at ≥100 mg/kg/day, which produced plasma exposures (AUCs) of doxepin and nordoxepin (the primary metabolite in humans) approximately 65 and 53 times, respectively, the plasma AUCs at the MRHD.
The plasma exposures at the no-effect dose for embryo-fetal developmental toxicity in rats (30 mg/kg/day) are approximately 6 and 5 times the plasma AUCs for doxepin and nordoxepin, respectively, at the MRHD. When doxepin (10, 30, and 60 mg/kg/day) was administered orally to pregnant rabbits during the period of organogenesis, fetal body weights were reduced at the highest dose in the absence of maternal toxicity, which produced plasma AUCs of doxepin and nordoxepin approximately 23 and 56 times, respectively, the plasma AUCs at the MRHD.
The plasma exposures at the no-effect dose for developmental effects (30 mg/kg/day) are approximately 8 and 25 times the plasma AUCs for doxepin and nordoxepin, respectively, at the MRHD. Oral administration of doxepin (10, 30, and 100 mg/kg/day) to rats throughout pregnancy and lactation resulted in decreased pup survival and transient growth delay at the highest dose, which produced plasma AUCs of doxepin and nordoxepin approximately 60 and 39 times, respectively, the plasma AUCs at the MRHD. The plasma exposures at the no-effect dose for adverse effects on pre- and postnatal development in rats (30 mg/kg/day) are app…
🧒 Pediatric Use ▾
8.4. Pediatric Use The safety and effectiveness of Doxepin HCl Tablets in pediatric patients have not been evaluated.
🧓 Geriatric Use ▾
8.5. Geriatric Use A total of 362 subjects who were ≥ 65 years and 86 subjects who were ≥ 75 years received Doxepin HCl Tablets in controlled clinical studies. No overall differences in safety or effectiveness were observed between these subjects and younger adult subjects.
Greater sensitivity of some older individuals cannot be ruled out. Sleep-promoting drugs may cause confusion and over-sedation in the elderly. A starting dose of 3 mg is recommended in this population and evaluation prior to considering dose escalation is recommended [see Dosage and Administration (2.2) ] .
🆘 Overdosage ▾
10. OVERDOSAGE Doxepin is routinely administered for indications other than insomnia at doses 10- to 50-fold higher than the highest recommended dose of Doxepin HCl Tablets. The signs and symptoms associated with doxepin use at doses several-fold higher than the maximum recommended dose (Excessive dose) of Doxepin HCl Tablets for the treatment of insomnia are described [see Overdosage (10.1) ] , as are signs and symptoms associated with higher multiples of the maximum recommended dose (Critical overdose) [see Overdosage (10.2) ] .
10.1. Signs and Symptoms of Excessive Doses The following adverse effects have been associated with use of doxepin at doses higher than 6 mg. Anticholinergic Effects: constipation and urinary retention.
Central Nervous System: disorientation, hallucinations, numbness, paresthesias, extrapyramidal symptoms, seizures, tardive dyskinesia. Cardiovascular: hypotension. Gastrointestinal: aphthous stomatitis, indigestion.
Endocrine: raised libido, testicular swelling, gynecomastia in males, enlargement of breasts and galactorrhea in the female, raising or lowering of blood sugar levels, and syndrome of inappropriate antidiuretic hormone secretion. Other: tinnitus, weight gain, sweating, flushing, jaundice, alopecia, exacerbation of asthma, and hyperpyrexia (in association with chlorpromazine). 10.2.
Signs and Symptoms of Critical Overdose Manifestations of doxepin critical overdose include: cardiac dysrhythmias, severe hypotension, convulsions, and CNS depression including coma. Electrocardiogram changes, particularly in QRS axis or width, are clinically significant indicators of tricyclic compound toxicity. Other signs of overdose may include, but are not limited to: confusion, disturbed concentration, transient visual hallucinations, dilated pupils, agitation, hyperactive reflexes, stupor, drowsiness, muscle rigidity, vomiting, hypothermia, hyperpyrexia.
10.3. Recommended Management As management of overdose is complex and changing, it is recommended that the physician contact a poison control center for current information on treatment. In addition, the possibility of a multiple drug ingestion should be considered.
If an overdose is suspected, an ECG should be obtained and cardiac monitoring should be initiated immediately. The patient's airway should be protected, an intravenous line should be established, and gastric decontamination should be initiated. 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 overdose should receive gastrointestinal decontamination. This should include large volume gastric lavage followed by administration of 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 an overdose. Serum alkalinization, using intravenous sodium bicarbonate should be used to maintain the serum pH in the range of 7.45 to 7.55 for patients with dysrhythmias and/or QRS widening.
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 pCO 2 <20 mm Hg is undesirable.
Dysrhythmias unresponsive to sodium bicarbonate therapy/hyperventilation may respond to lidocaine…
🧬 Clinical Pharmacology ▾
12. CLINICAL PHARMACOLOGY 12.1. Mechanism of Action The mechanism of action of doxepin in sleep maintenance is unclear; however, doxepin's effect could be mediated through antagonism of the H 1 receptor.
12.2. Pharmacodynamics Doxepin has high binding affinity to the H 1 receptor (Ki < 1 nM) Cardiac Electrophysiology In a thorough QTc prolongation clinical study in healthy subjects, doxepin had no effect on QT intervals or other electrocardiographic parameters after multiple daily doses up to 50 mg. 12.3.
Pharmacokinetics Absorption The median time to peak concentrations (T max ) of doxepin occurred at 3.5 hours postdose after oral administration of a 6 mg dose to fasted healthy subjects. Peak plasma concentrations (C max ) of Doxepin HCl Tablets increased in approximately a dose-proportional manner for 3 mg and 6 mg doses. The AUC was increased by 41% and C max by 15% when 6 mg Doxepin HCl Tablets was administered with a high fat meal.
Additionally, compared to the fasted state, T max was delayed by approximately 3 hours. Therefore, for faster onset and to minimize the potential for next day effects, it is recommended that Doxepin HCl Tablets not be taken within 3 hours of a meal [see Dosage and Administration (2.3) ] . Distribution Doxepin HCl Tablets is widely distributed throughout the body tissues.
The mean apparent volume of distribution following a single 6 mg oral dose of Doxepin HCl Tablets to healthy subjects was 11,930 liters. Doxepin HCl Tablets is approximately 80% bound to plasma proteins. Metabolism Following oral administration, Doxepin HCl Tablets is extensively metabolized by oxidation and demethylation.
The primary metabolite is N-desmethyldoxepin (nordoxepin). The primary metabolite undergoes further biotransformation to glucuronide conjugates. In vitro studies have shown that CYP2C19 and CYP2D6 are the major enzymes involved in doxepin metabolism, and that CYP1A2 and CYP2C9 are involved to a lesser extent.
Doxepin appears not to have inhibitory effects on human CYP enzymes at therapeutic concentrations. The potential of doxepin to induce metabolizing enzymes is not known. Doxepin is not a Pgp substrate.
Excretion Doxepin is excreted in the urine mainly in the form of glucuronide conjugates. Less than 3% of a doxepin dose is excreted in the urine as parent compound or nordoxepin.The apparent terminal half-life (t ½) of doxepin was 15.3 hours and for nordoxepin was 31 hours. Drug Interactions Since doxepin is metabolized by CYP2C19 and CYP2D6, inhibitors of these CYP isozymes may increase the exposure of doxepin.
Cimetidine The effect of cimetidine, a non-specific inhibitor of CYP1A2, 2C19, 2D6, and 3A4, on Doxepin HCl Tablets plasma concentrations was evaluated in healthy subjects. When cimetidine 300 mg BID was co-administered with a single dose of Doxepin HCl Tablets 6 mg, there was approximately a 2-fold increase in Doxepin HCl Tablets C max and AUC compared to Doxepin HCl Tablets given alone. A maximum dose of doxepin in adults and elderly should be 3 mg, when doxepin is co-administered with cimetidine.
Sertraline The effect of sertraline HCl, a selective serotonin reuptake inhibitor, on doxepin plasma concentrations was evaluated in a daytime study conducted with 24 healthy subjects. Following co-administration of doxepin 6 mg with sertraline 50 mg (at steady-state), the doxepin mean AUC and C max estimates were approximately 21% and 32% higher, respectively, than those obtained following administration of doxepin alone. Psychomotor function as measured by the digit symbol substitution test and symbol copy test performance was decreased more at 2-4 hours post dosing for the combination of sertraline and doxepin as compared to doxepin alone, but subjective measures of alertness were comparable for the two treatments.
Special Populations Renal Impairment The effects of renal impairment on doxepin pharmacokinetics have not been studied. Because only small amounts of doxepin and nordoxepin are eliminated i…
🧬 Mechanism of Action ▾
12.1. Mechanism of Action The mechanism of action of doxepin in sleep maintenance is unclear; however, doxepin's effect could be mediated through antagonism of the H 1 receptor.
📦 How Supplied / Storage and Handling ▾
16. HOW SUPPLIED/STORAGE AND HANDLING 16.1. How Supplied Doxepin HCl Tablets 3 mg tablets are oval shaped, blue, identified with debossed markings of "3" on one side and "SP" on the other, and are supplied as: NDC 44183-103-30 Bottle of 30 Doxepin HCl Tablets 6 mg tablets are oval shaped, green, identified with debossed markings of "6" on one side and "SP" on the other, and are supplied as: NDC 44183-106-30 Bottle of 30 16.2.
Storage and Handling Store at controlled room temperature 20° - 25°C (68° - 77°F), protected from light.
📦 Storage and Handling ▾
16.2. Storage and Handling Store at controlled room temperature 20° - 25°C (68° - 77°F), protected from light.
📋 Description ▾
11. DESCRIPTION Doxepin HCl Tablets is available in 3 mg and 6 mg strength tablets for oral administration. Each tablet contains 3.39 mg or 6.78 mg doxepin hydrochloride, equivalent to 3 mg and 6mg of doxepin, respectively.
Chemically, doxepin hydrochloride is an (E) and (Z) geometric, isomeric mixture of 1 propanamine, 3-dibenz [b,e] oxepin-11(6 H )ylidene- N,N -dimethyl-hydrochloride. It has the following structure: Doxepin hydrochloride is a white crystalline powder, with a slight amine-like odor, that is readily soluble in water. It has a molecular weight of 315.84 and molecular formula of C 19 H 21 NO∙HCl.
Each Doxepin HCl Tablets tablet includes the following inactive ingredients: microcrystalline cellulose, colloidal silicon dioxide, and magnesium stearate. The 3 mg tablet also contains FD&C Blue No.1. The 6 mg tablet also contains D&C Yellow No.
10 and FD&C Blue No. 1. Chemical Structure
💬 Information for Patients ▾
17. PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Medication Guide). Sleep-driving and Other Complex Behaviors There have been reports of people getting out of bed after taking a hypnotic and driving their cars while not fully awake, often with no memory of the event.
If a patient experiences such an episode, it should be reported to his or her doctor immediately, since "sleep-driving" can be dangerous. This behavior is more likely to occur when a hypnotic is taken with alcohol or other central nervous system depressants [see Warnings and Precautions (5.2 , 5.4) and Drug Interactions (7.3 , 7.4) ] . Other complex behaviors (e.g., preparing and eating food, making phone calls, or having sex) have been reported in patients who are not fully awake after taking a hypnotic.
As with "sleep-driving", patients usually do not remember these events. In addition, patients should be advised to report all concomitant medications to the prescriber. Patients should be instructed to report events such as "sleep-driving" and other complex behaviors immediately to the prescriber.
Suicide risk and Worsening of Depression Patients, their families, and their caregivers should be encouraged to be alert to worsening of depression, including suicidal thoughts and actions. Such symptoms should be reported to the patient's prescriber or health professional. Administration Instructions Patients should be counseled to take Doxepin HCl Tablets within 30 minutes of bedtime and should confine their activities to those necessary to prepare for bed.
Doxepin HCl Tablets tablets should not be taken with or immediately after a meal [see Dosage and Administration (2.3) ] . Advise patients NOT to take Doxepin HCl Tablets when drinking alcohol [see Warnings and Precautions (5.2 , 5.4) and Drug Interactions (7.3) ] . Pregnancy Advise patients that Doxepin HCl Tablets use late in pregnancy may increase the risk for neonatal complications requiring prolonged hospitalization, respiratory support or tube feeding [see Use in Specific Populations (8.1) ] .
Lactation Advise patients that breastfeeding is not recommended during treatment with Doxepin HCl Tablets [see Use in Specific Populations (8.2) ] . Infertility Inform patients that Doxepin HCl Tablets may cause reduced fertility. It is not known whether these effects on fertility are reversible [see Use in Specific Populations (8.3) and Nonclinical Toxicology (13.1) ] .
💬 Medication Guide ▾
This Medication Guide has been approved by the U.S. Food and Drug Administration. Revised: 11/2021 005PIL01 MEDICATION GUIDE Doxepin HCl Tablets What is the most important information I should know about Doxepin HCl Tablets?
Doxepin HCl Tablets can cause serious side effects including: After taking Doxepin HCl Tablets, you may get up out of bed while not being fully awake and do an activity that you do not know you are doing. The next morning, you may not remember that you did anything during the night. You have a higher chance for doing these activities if you drink alcohol or take other medicines that make you sleepy with Doxepin HCl Tablets.
Reported activities include: driving a car ("sleep-driving") making and eating food talking on the phone having sex sleep-walking Stop taking Doxepin HCl Tablets and call your healthcare provider right away if you find out that you have done any of the above activities after taking Doxepin HCl Tablets. Important: Take Doxepin HCl Tablets exactly as prescribed Do not take more Doxepin HCl Tablets than prescribed. Take Doxepin HCl Tablets 30 minutes before bedtime.
After taking Doxepin HCl Tablets, you should only do activities needed to get ready for bed. What is Doxepin HCl Tablets? Doxepin HCl Tablets is a prescription medicine used to treat adults who have trouble staying asleep.
It is not known if Doxepin HCl Tablets is safe and effective in children. Do not take Doxepin HCl Tablets if you: are allergic to any of the ingredients in Doxepin HCl Tablets. See the end of this Medication Guide for a complete list of ingredients in Doxepin HCl Tablets. take a monoamine oxidase inhibitor (MAOI) medicine or have taken an MAOI in the last 14 days (2 weeks).
Ask your healthcare provider if you are not sure if your medicine is an MAOI. have an eye problem called narrow angle glaucoma that is not being treated or have trouble urinating that is severe. Before taking Doxepin HCl Tablets, tell your healthcare provider about all of your medical conditions, including if you: have a history of depression, mental illness, or suicidal thoughts have severe sleep apnea have kidney or liver problems have a history of drug or alcohol abuse or addiction have a history of glaucoma or trouble urinating that is severe have any other medical conditions are pregnant or plan to become pregnant.
Taking Doxepin HCl Tablets in the third trimester of pregnancy may harm your unborn baby. Talk to your healthcare provider if you are pregnant or plan to become pregnant during treatment with Doxepin HCl Tablets. Babies born to mothers who take certain medicines, including Doxepin HCl Tablets, during the third trimester of pregnancy may have symptoms of sedation, such as breathing problems, sluggishness, low muscle tone, feeding problems, and withdrawal symptoms. are breastfeeding or plan to breastfeed.
Doxepin HCl Tablets can pass into your breast milk and may harm your baby. You should not breastfeed during treatment with Doxepin HCl Tablets. Talk to your healthcare provider about the best way to feed your baby during treatment with Doxepin HCl Tablets.
Tell your healthcare provider about all of the medicines you take including prescription and over-the-counter medicines, vitamins and herbal supplements. Doxepin HCl Tablets and other medicines may affect each other causing side effects. Doxepin HCl Tablets may affect the way other medicines work, and other medicines may affect how Doxepin HCl Tablets works.
Especially tell your healthcare provider if you take: certain allergy medicines (antihistamines) or other medicines that can make you sleepy or affect your breathing Know the medicines you take. Keep a list of your medicines with you to show your healthcare provider and pharmacist each time you get a new medicine. How should I take Doxepin HCl Tablets?
Take Doxepin HCl Tablets exactly as your healthcare provider tells you to take it. Your healthcare provider may change your dose if needed. Take Doxepin HCl Tablets with…