doxepin
Trade name: sinequan
Approved
Sep 23, 1969
Doxepin is a dibenzoxepin tricyclic antidepressant marketed worldwide. It is a white crystalline solid readily soluble in water, lower alcohols and chloroform. The mechanism of action of doxepin is not definitely known. It is not a central nervous system stimulant nor a monoamine oxidase inhibitor. The current hypothesis is that the clinical effects are due, at least in part, to influences on the adrenergic activity at the synapses so that deactivation of norepinephrine by reuptake into the nerve terminals is prevented. Antidepressants may increase risk of suicidal thinking and behavior (suicidality) in children, adolescents, and young adults (18–24 years of age) with major depressive disorder and other psychiatric disorders. Drowsiness is the most commonly noticed side effect. This tends to disappear as therapy is continued. Other infrequently reported CNS side effects are confusion, disorientation, hallucinations, numbness, paresthesias, ataxia, extrapyramidal symptoms, seizures, tardive dyskinesia, and tremor. : Cardiovascular effects including hypotension, hypertension, and tachycardia have been reported occasionally. Skin rash, edema, photosensitization, and pruritus have occasionally occurred. Eosinophilia has been reported in a few patients. There have been occasional reports of bone marrow depression manifesting as agranulocytosis, leukopenia, thrombocytopenia, and purpura. Doxepin is used to treat depression, anxiety disorders, itchiness, trouble sleeping, and as a second-line treatment of chronic idiopathic urticaria (hives). Its oral formulations are FDA-approved for the treatment of depression, anxiety, and insomnia and its topical formulations are FDA-approved the short-term management (up to 8 days) of atopic dermatitis and lichen simplex chronicus. Whereas in Australia and the UK, the only licensed indication(s) is/are in the treatment of major depression and pruritus in eczema, respectively. — NCATS
Clinical trial activity
17 trials · 18 clinical orgs · 39 marketing orgs
Earliest trial started Jul 1, 2006 (NCT00755495)
Timeline
1960s
1970s
- Jan 31, 1972
New River Pharmaceuticals — NDA Secondary Org
1980s
- May 13, 1986
Mylan — Marketing Organization
- May 15, 1986
Sandoz — Marketing Organization
- Apr 30, 1987
Watson Pharmaceuticals — Marketing Organization
- Nov 9, 1987
Par Pharmaceuticals — Marketing Organization
- Nov 9, 1987
Teva — Marketing Organization
- Feb 18, 1988
Sun Pharmaceuticals — Marketing Organization
- Jul 20, 1988
Wockhardt — Marketing Organization
- Jul 20, 1988
Xttrium Laboratories — Marketing Organization
1990s
- Dec 28, 1990
Puracap Pharmaceutical — Marketing Organization
- Apr 1, 1994
Mylan — NDA Secondary Org
- Dec 29, 1998
Lannett Company, Inc. — Marketing Organization
2000s
- Jan 15, 2004
Pharmaceutical Associates — Marketing Organization
- Jan 1, 2006
Earliest Phase 2 Sponsor(trial)
2010s
- Jan 1, 2010
Earliest Phase 3 Sponsor(trial)
- Mar 17, 2010
Currax Pharmaceuticals — Marketing Organization
- Mar 17, 2010
Pernix — NDA Secondary Org
- Mar 17, 2010
Currax Pharmaceuticals — NDA Secondary Org
- Jan 1, 2011
Earliest Phase 1 Sponsor(trial)
- Feb 22, 2013
Zydus Discovery DMCC — Marketing Organization
- Jul 26, 2013
Actavis — Marketing Organization
- Jan 20, 2016
Apicore — Marketing Organization
- Jun 28, 2017
Amneal Pharmaceuticals — Marketing Organization
- Mar 27, 2019
Aurobindo Pharma — Marketing Organization
- Sep 13, 2019
Ajanta Pharma Ltd — Marketing Organization
2020s
- Jul 1, 2020
Taro Pharmaceuticals — Marketing Organization
- Jul 24, 2020
Strides Pharma Science — Marketing Organization
- Jul 28, 2020
Contract Pharmacal — Marketing Organization
- Sep 4, 2020
Upsher-Smith Laboratories — Marketing Organization
- Sep 4, 2020
Chartwell Pharmaceuticals — Marketing Organization
- Oct 16, 2020
Epic Pharma Llc — Marketing Organization
- Mar 1, 2021
Leading Pharma Llc — Marketing Organization
- Apr 1, 2021
Appco Pharma — Marketing Organization
- Apr 21, 2021
Alembic — Marketing Organization
- Feb 9, 2022
Mankind Pharma — Marketing Organization
- Mar 14, 2022
Jubilant Innovation Ltd. — Marketing Organization
- Apr 19, 2022
Edenbridge Pharms — Marketing Organization
- Jun 24, 2022
MSN Laboratories — Marketing Organization
- Jun 27, 2023
Micro Labs Ltd India — Marketing Organization
- Aug 21, 2023
Unique Pharmaceuticals Ltd, India — Marketing Organization
Indications
Studied for
- Acute Pain · Phase 3
- Anxiety Disorders · Phase 3
- Breast Neoplasms · Phase 2
- Dementia · Phase 3
- Depression · Phase 3
- Head and Neck Neoplasms · Phase 3
- Healthy Volunteers · Phase 4
- HIV Infections · Phase 4
- Irritable Bowel Syndrome · Phase 2
- Mucositis · Phase 3
- Pain · Phase 3
- Parkinson Disease · Early Phase 1
- Pruritus · Phase 4
- Psychophysiologic Disorders · Phase 3
- Radiation Oncology · Phase 3
- Schizophrenia · Phase 3
- Sleep Initiation and Maintenance Disorders · Phase 4
- Urticaria · Phase 3
Mechanism of action
- Histamine H1 receptorANTAGONIST
HRH1 antagonist
- Norepinephrine transporterANTAGONIST
SLC6A2 antagonist
Approval history
- approvedSep 23, 1969
Chemistry & pharmacology
SMILES
CN(C)CCC=C1c2ccccc2COc2ccccc21- Mol. weight
- 279.38 g/mol
- Lipinski Ro5
- Pass
- Rule of 3
- No
- Chirality
- Achiral Molecule
- Inorganic
- No
- Polymer
- No
- Delivery
- Oral, Topical
- Availability
- Prescription Only
Oral
Yes
Parenteral
No
Topical
Yes
Sources
- ChEMBLCHEMBL1628227 ↗
- WikipediaDoxepin ↗
- NCATS5ASJ6HUZ7D ↗
- ChEMBLCHEMBL1628234 ↗
Also known as
- doxepin
- doxepin
- doxepin
- doxepin
- doxepin
- doxepin hcl
- doxepin hcl
- doxepin hcl
- doxepin hydrochloride
- doxepin hydrochloride
- doxepin hydrochloride
- doxepin hydrochloride
- doxepin hydrochloride
- quitaxon
- quitaxon
- silenor
- silenor
- silenor
- sinepin
- sinequan
- sinequan
- xepin
- xepin
- zonalon
- zonalon
Clinical trials
| NCT ID | Phase | Start date | Sponsor(s) |
|---|---|---|---|
| NCT06017895 | N/A | Nov 1, 2023 | Southern Medical University |
| NCT05607056 | N/A | Nov 27, 2022 | Medical University of Sofia, Neopharm |
| NCT05115136 | Phase 3 | Nov 8, 2021 | State University of New York, Syracuse |
| NCT04554888 | N/A | Nov 1, 2020 | Aalborg University |
| NCT04588532 | N/A | Oct 31, 2020 | Aalborg University |
| NCT03943407 | N/A | Jun 30, 2019 | Aalborg University |
| NCT03758079 | Phase 4 | Jun 1, 2018 | University of Balamand |
| NCT02447211 | Phase 2 | May 1, 2015 | Iran University of Medical Sciences, Isfahan Milad Hospital, Isfahan University |
| NCT02374567 | Phase 3 | Jan 1, 2015 | Gottfried Wilhelm Leibniz Universität Hannover |
| NCT02353299 | Phase 4 | Jan 1, 2015 | Henry Ford Health System, Pernix |
| NCT02229539 | Phase 3 | Nov 1, 2014 | Mayo Clinic, National Cancer Institute (NCI) |
| NCT02062632 | N/A | Apr 14, 2014 | Mayo Clinic, National Cancer Institute (NCI) |
| NCT01489982 | Early Phase 1 (Phase 1) | Jan 1, 2011 | McGill University |
| NCT01268709 | Phase 2 | Dec 30, 2010 | Qom University of Medical Sciences |
| NCT01156142 | Phase 3 | Dec 1, 2010 | Mayo Clinic, National Cancer Institute (NCI) |
| NCT00465972 | Phase 4 | Mar 1, 2007 | Duke University |
| NCT00755495 | Phase 2 | Jul 1, 2006 | Takeda |
Organizations
Research & Development (18)
| Organization | Org type | Trials | As lead sponsor | Phases | Earliest year |
|---|---|---|---|---|---|
| Aalborg University | Academic/Hospital | 3 | 3 | 1 | 2019 |
| Mayo Clinic | Academic/Hospital | 3 | 1 | 2 | 2010 |
| National Cancer Institute (NCI) | Government | 3 | 2 | 2 | 2010 |
| Duke University | Academic/Hospital | 1 | 1 | 1 | 2007 |
| Gottfried Wilhelm Leibniz Universität Hannover | Academic/Hospital | 1 | 1 | 1 | 2015 |
| Henry Ford Health System | Academic/Hospital | 1 | 0 | 1 | 2015 |
| Iran University of Medical Sciences | Academic/Hospital | 1 | 0 | 1 | 2015 |
| Isfahan Milad Hospital | Academic/Hospital | 1 | 0 | 1 | 2015 |
| Isfahan University | Academic/Hospital | 1 | 1 | 1 | 2015 |
| McGill University | Academic/Hospital | 1 | 1 | 1 | 2011 |
| Medical University of Sofia | Academic/Hospital | 1 | 0 | 1 | 2022 |
| Neopharm | For profit | 1 | 1 | 1 | 2022 |
| Pernix | For profit | 1 | 1 | 1 | 2015 |
| Qom University of Medical Sciences | Academic/Hospital | 1 | 1 | 1 | 2010 |
| Southern Medical University | Academic/Hospital | 1 | 1 | 1 | 2023 |
| State University of New York, Syracuse | Academic/Hospital | 1 | 1 | 1 | 2021 |
| Takeda | For profit | 1 | 1 | 1 | 2006 |
| University of Balamand | Academic/Hospital | 1 | 1 | 1 | 2018 |
Marketing (52)
| Organization | Org type | Relationship | Date |
|---|---|---|---|
| Actavis | For profit | MKTG | Jul 26, 2013 |
| Ajanta Pharma Ltd | For profit | MKTG | Sep 13, 2019 |
| Alembic | For profit | MKTG | Apr 21, 2021 |
| Alembic | For profit | SYN | Apr 21, 2021 |
| Amneal Pharmaceuticals | For profit | MKTG | Jun 28, 2017 |
| Amneal Pharmaceuticals | For profit | SYN | Aug 16, 2023 |
| Apicore | For profit | MKTG | Jan 20, 2016 |
| Appco Pharma | For profit | MKTG | Apr 1, 2021 |
| Aurobindo Pharma | For profit | MKTG | Mar 27, 2019 |
| Chartwell Pharmaceuticals | For profit | MKTG | Sep 4, 2020 |
| Contract Pharmacal | For profit | MKTG | Jul 28, 2020 |
| Currax Pharmaceuticals | For profit | MKTG | Mar 17, 2010 |
| Currax Pharmaceuticals | For profit | NDA2 | Mar 17, 2010 |
| DAVA Pharmaceuticals | For profit | MKTG | — |
| Edenbridge Pharms | For profit | MKTG | Apr 19, 2022 |
| Epic Pharma Llc | For profit | MKTG | Oct 16, 2020 |
| Jubilant Innovation Ltd. | For profit | MKTG | Mar 14, 2022 |
| Lannett Company, Inc. | For profit | MKTG | Dec 29, 1998 |
| Leading Pharma Llc | For profit | MKTG | Mar 1, 2021 |
| Leading Pharma Llc | For profit | MKTG | Mar 1, 2021 |
| MSN Laboratories | For profit | MKTG | Jun 24, 2022 |
| Mankind Pharma | For profit | MKTG | Feb 9, 2022 |
| Micro Labs Ltd India | For profit | MKTG | Jun 27, 2023 |
| Mylan | For profit | MKTG | May 13, 1986 |
| Mylan | For profit | SYN | May 13, 1986 |
| Mylan | For profit | NDA2 | Apr 1, 1994 |
| New River Pharmaceuticals | For profit | NDA2 | Jan 31, 1972 |
| Par Pharmaceuticals | For profit | MKTG | Nov 9, 1987 |
| Par Pharmaceuticals | For profit | SYN | Jul 24, 2020 |
| Pernix | For profit | NDA2 | Mar 17, 2010 |
| Pfizer | For profit | NDA2 | Sep 23, 1969 |
| Pharmaceutical Associates | For profit | MKTG | Jan 15, 2004 |
| Puracap Pharmaceutical | For profit | MKTG | Dec 28, 1990 |
| Quantum Pharmaceutical | For profit | MKTG | — |
| Roche | For profit | NDA | Sep 23, 1969 |
| Sandoz | For profit | MKTG | May 15, 1986 |
| Strides Pharma Science | For profit | MKTG | Jul 24, 2020 |
| Strides Pharma Science | For profit | MKTG | Jul 24, 2020 |
| Sun Pharmaceuticals | For profit | MKTG | Feb 18, 1988 |
| Taro Pharmaceuticals | For profit | MKTG | Jul 1, 2020 |
| Taro Pharmaceuticals | For profit | SYN | Jul 1, 2020 |
| Teva | For profit | SYN | Nov 9, 1987 |
| Teva | For profit | SYN | Mar 29, 1991 |
| Teva | For profit | MKTG | Nov 9, 1987 |
| Unique Pharmaceuticals Ltd, India | For profit | MKTG | Aug 21, 2023 |
| Upsher-Smith Laboratories | For profit | MKTG | Sep 4, 2020 |
| Watson Pharmaceuticals | For profit | MKTG | Apr 30, 1987 |
| Wockhardt | For profit | MKTG | Jul 20, 1988 |
| Xttrium Laboratories | For profit | MKTG | Jul 20, 1988 |
| Zydus Discovery DMCC | For profit | MKTG | Feb 22, 2013 |
| Zydus Discovery DMCC | For profit | SYN | Mar 21, 2023 |
| Zydus Discovery DMCC | For profit | SYN | Aug 16, 2023 |