| Regulatorische Informationen | Doxepin: Does not have an individual approval but may be used under an appropriate group standard |
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| Weitere Sicherheitsinformationen | IMAP assessments - 1-Propanamine, 3-dibenz[b,e]oxepin-11(6H)-ylidene-N,N-dimethyl-: Human health tier I assessment |
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| FDA-Anforderungen | Manufacturers, packers, and distributors of drug and drug products for human use are responsible for complying with the labeling, certification, and usage requirements as prescribed by the Federal Food, Drug, and Cosmetic Act, as amended (secs 201-902, 52 Stat. 1040 et seq., as amended21 U.S.C. 321-392). |
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| Lagerbedingungen | Doxepin hydrochloride capsules and oral concentrate should be protected from direct sunlight and stored in well-closed and tight, light-resistant containers, respectively, at a temperature between 15 and 30 °C. /Doxepin hydrochloride/ |
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| Entsorgungsverfahren | SRP: At the time of review, criteria for land treatment or burial (sanitary landfill) disposal practices are subject to significant revision. Prior to implementing land disposal of waste residue (including waste sludge), consult with environmental regulatory agencies for guidance on acceptable disposal practices. |
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| Treatment | Obtain an ECG and immediately initiate cardiac monitoring. Protect the patient's airway, establish an intravenous line and initiate gastric decontamination. 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. (L1712) |
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| Wechselwirkungen | /DOXEPIN/...MAY...POTENTIATE THE DEPRESSANT EFFECT OF ALCOHOL. /HYDROCHLORIDE/INHIBITION OF THE ANTIHYPERTENSIVE EFFECT OF GUANETHIDINE CAN OCCUR WITH DOSES OF 200-300 MG/DAY. /HYDROCHLORIDE/DOXEPIN MAY POTENTIATE ORAL ANTICOAGULANTS, AMPHETAMINES, OTHER ANTICHOLINERGICS, MEPROBAMATE, PHENOTHIAZINES, THIOXANTHENE TRANQUILIZERS. DOXEPIN MAY ANTAGONIZE PROPRANOLOL /THEORETICALLY/, METHYLDOPA. DOXEPIN MAY BE ANTAGONIZED BY BARBITURATES. DOXEPIN MAY BE POTENTIATED BY THYROID PREPN.DOXEPIN MAY FORM HAZARDOUS COMBINATIONS WITH RESERPINE, ESTROGENS, PSYCHOTROPICS, MAO INHIBITORS, BENZODIAZEPINES.For more Interactions (Complete) data for DOXEPIN (28 total), please visit the HSDB record page. |
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| Gesundheitliche Auswirkungen | hypotension, postural collapse (if patient arises too fast from lying/sitting position to standing), arrhythmias (sinus-tachycardia, bradycardia, av-blockade). Allergic/toxic effetcs also include skin rash, photosensitivity, liver damage of the cholostatic type (rarely), hepatitis (extremely rare), leuko- or thrombopenia (rarely), agranulocytosis (very rarely), hypoplastic anemia (rarely). [Wikipedia] |
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| Hepatotoxicity | Liver test abnormalities have been reported to occur in up to 16% of patients being treated with tricyclic antidepressants, but elevations are uncommonly above 3 times the upper limit of normal. The aminotransferase abnormalities are usually mild, asymptomatic and transient, reversing even with continuation of medication. Rare instances of clinically apparent acute liver injury have been reported due to doxepin, but the number of cases have been too few to characterize the clinical features. Recurrent jaundice and marked aminotransferase elevations with repeated exposures to doxepin has been reported. Most cases have been mild and deaths from acute liver failure or chronic injury have not been reported. |
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| Unerwünschte Wirkungen | Doxepin is a unique antidepressant because it produces different adverse effects based on the receptor it antagonizes. Doxepin antagonizes 3 different receptors: histamine, adrenergic, and muscarinic. Doxepin blocks histamine H1 receptor and causes sedation and somnolencetherefore, FDA has approved low-dose doxepin, 3 mg, and 6 mg dosages as a first-line agent in depressed patients with sleep disturbances and depression associated with anxiety. Proper education is necessary to prevent patients from self-medicating and overdosing with these doses. |
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| Expositionspfade | Well-absorbed from the GI tract. Peak plasma concentrations occur within 2 hours of oral administration. |
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| Toxizitätsübersicht | TCAs are one of the most frequently ingested substances used for self-poison in an attempt to commit suicide. A case fatality index is a tool used to measure ratios and compare toxic levels of drugs to one another. Tricyclics have a greater incidence of toxicity than other antidepressants, and doxepin is 2 to 3 times more toxic when compared to amitriptyline.The mechanism of action of doxepin is not completely understood. It is thought that like amitriptyline, doxepin enhances the actions of norepinephrine and serotonin by blocking their reuptake at the neuronal membrane. However, doxepin weakly inhibits the reuptake of dopamine. Doxepin may also act on histamine H<sub>1</sub>-receptors, resulting in sedative effects, and &beta-adrenergic receptors. It is also an antagonist of 5-hydroxytryptamine (serotonin) receptors, alpha-1 adrenergic receptor, and muscarinic cholinergic receptors. |
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| Signs and Symptoms | Cardiac dysrhythmias, severe hypotension, convulsions, and CNS depression, including coma. Changes in the electrocardiogram, particularly in QRS axis or width, are clinically significant indicators of tricyclic antidepressant toxicity. |
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| Human Toxicity Excerpts | ALTHOUGH MOST FATAL CASES OF DOXEPIN POISONING HAVE RESULTED FROM INGESTION OF MORE THAN 1.5 G, DEATH HAS BEEN REPORTED AFTER INGESTION OF 850 MG & RECOVERY AFTER...5 G. /HYDROCHLORIDE/DOXEPIN OVERDOSE PATIENTS SHOWED QRS DURATION OF 100 MSEC OR MORE ON ROUTINE ECG WITHIN 1ST 24 HR.A 36-year-old woman was treated with doxepin, 10 mg daily, for approximately 5 weeks starting 2 weeks after the birth of her daughter. The dose was increased to 25 mg three times daily 4 days before the wholly breast-fed 8-week-old infant was found pale, limp, and near respiratory arrest. Although drowsiness and shallow respirations continued on admission to the hospital, the baby made a rapid recovery and was normal in 24 hours. |
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| Carcinogen Classification | No indication of carcinogenicity to humans (not listed by IARC). |
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| Drug Induced Liver Injury | Drug-Induced Liver Injury Severity and Toxicity (DILIst)doxepinDILI PositiveOralDOI:10.1016/j.drudis.2019.09.022 |
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| Non-Human Toxicity Excerpts | IN PUPPIES GIVEN WEEKLY INFUSIONS, IMIPRAMINE WAS LESS ARRHYTHMOGENIC & CAUSED LESS FALL IN BLOOD PRESSURE FOR GIVEN DOSE THAN AMITRIPTYLINE OR DOXEPIN. |
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