Doxepin

279.38

279.38

214-966-8

DTXSID7022966

OILY LIQUID CONSISTING OF A MIXTURE OF CIS- & TRANS- ISOMERS

D - Dermatologicals|N - Nervous system

2932999099

12.47000

3.96240

1.0594 (rough estimate)

<25 °C

154-157 °C @ Press: 0.03 Torr

121.3ºC

1.5000 (estimate)

1.13e-04 M

Store at RT

LD50 in mice, rats (mg/kg): 26, 16 i.v.; 79, 182 i.p.; 135, 147 orally (Ribbentrop, Schaumann)

ODORLESS

BITTER

164.3 Ų [M+H]+ [CCS Type: TW, Method: Major Mix IMS/Tof Calibration Kit (Waters)]

White crystalline solid, readily soluble in water, lower alcohols, and chloroform. /DOXEPIN HYDROCHLORIDE/

25

36/37/39-45

T

DECOMP SLOWLY IN LIGHT, NONHYGROSCOPIC UP TO 75% RELATIVE HUMIDITY, RELATIVELY STABLE IN HEAT /HYDROCHLORIDE/

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.

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 amended; 21 U.S.C. 321-392).

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.

/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.

LD50 Rat oral 147 mg/kg|LD50 Rat ip 182 mg/kg|LD50 Rat iv 16 mg/kg|LD50 Mouse oral 135 mg/kg|For more Non-Human Toxicity Values (Complete) data for DOXEPIN (7 total), please visit the HSDB record page.

Doxepin is a tricyclic antidepressant that widely used in the therapy of depression. Doxepin can cause mild and transient serum enzyme elevations but is a rare cause of clinically apparent acute cholestatic liver injury.

Antidepressant Agents

Adrenergic Uptake Inhibitors; Anti-Anxiety Agents; Antidepressive Agents, Tricyclic; Antipruritics|A DIBENZOXEPIN DERIVATIVE THAT IS A PSYCHOTHERAPEUTIC AGENT WITH ANTIANXIETY & ANTIDEPRESSANT PROPERTIES. ...RECOMMENDED FOR MGMNT OF ANXIETY &/OR DEPRESSIVE STATES ASSOCIATED WITH PSYCHONEUROSIS, PSYCHOSIS, ALCOHOLISM, & ORG DISEASE. /HYDROCHLORIDE/|VET: FOR RELIEF OF PRURITIS IN DERMATOSES IN DOGS. MILD TRANQUILIZING EFFECT IS NOTED AFTER PROLONGED THERAPY OR ON DOSES ABOVE THOSE RECOMMENDED.|Doxepin is indicated for the short-term (up to 8 days) topical treatment of moderate pruritus in adult patients with eczematous dermatitis, e.g., atopic dermatitis and lichen simplex chronicus. /Included in US product labeling; Doxepin, topical/|For more Therapeutic Uses (Complete) data for DOXEPIN (9 total), please visit the HSDB record page.

DOXEPIN HYDROCHLORIDE IS CONTRAINDICATED IN PT WITH GLAUCOMA OR TENDENCY TO URINARY RETENTION. ...SHOULD NOT BE ADMIN TO PT EITHER ON MAO INHIBITORS OR WHO HAVE BEEN...WITHIN THE PRIOR 2 WK. ...MAY...POTENTIATE DEPRESSANT EFFECT OF ALCOHOL. USE...IN PREGNANT PT OR...CHILDREN UNDER 12...NOT RECOMMENDED. /HYDROCHLORIDE/|ABOUT 2-3 WK MUST PASS BEFORE THERAPEUTIC EFFECTS...ARE EVIDENT. FOR THIS REASON, TRICYCLIC ANTIDEPRESSANTS SHOULD NEVER BE PRESCRIBED ON AN "AS-NEEDED" BASIS. ...SLOW ONSET OF EFFECTS MAY RELATE TO CHANGES IN METAB OF BIOGENIC AMINES THAT OCCUR... /IMIPRAMINE/|...GENERAL USE FOR HYPNOSIS IS NOT RECOMMENDED. IN ADEQUATE DOSES THEY CAUSE HANGOVER & ARE NOT AS EFFECTIVE AS A CONVENTIONAL HYPNOTIC. /TRICYCLIC ANTIDEPRESSANTS/|OCCASIONAL PT WILL SHOW PHYSICAL DEPENDENCE ON TRICYCLIC ANTIDEPRESSANTS, WITH MALAISE, CHILLS, CORYZA, & MUSCLE ACHING FOLLOWING ABRUPT DISCONTINUATION OF HIGH DOSES... /IMIPRAMINE/|For more Drug Warnings (Complete) data for DOXEPIN (25 total), please visit the HSDB record page.

4 OR 5. 4= VERY TOXIC: PROBABLE ORAL LETHAL DOSE (HUMAN) IS 50-500 MG/KG, BETWEEN 1 TEASPOON & 1 OUNCE FOR 70 KG PERSON (150 LB). 5= EXTREMELY TOXIC, PROBABLE ORAL LETHAL DOSE (HUMAN) IS 5-50 MG/KG, BETWEEN 7 DROPS & 1 TEASPOON FOR 70 KG PERSON (150 LB).

Substances that contain a fused three-ring moiety and are used in the treatment of depression. These drugs block the uptake of norepinephrine and serotonin into axon terminals and may block some subtypes of serotonin, adrenergic, and histamine receptors. However the mechanism of their antidepressant effects is not clear because the therapeutic effects usually take weeks to develop and may reflect compensatory changes in the central nervous system. (See all compounds classified as Antidepressive Agents, Tricyclic.)|Drugs that bind to but do not activate histamine receptors, thereby blocking the actions of histamine or histamine agonists. Classical antihistaminics block the histamine H1 receptors only. (See all compounds classified as Histamine Antagonists.)|Drugs used to induce SLEEP, prevent SLEEPLESSNESS, or treat SLEEP INITIATION AND MAINTENANCE DISORDERS. (See all compounds classified as Sleep Aids, Pharmaceutical.)

/DOXEPIN HAS/...A PECULIAR AFFINITY FOR UVEAL MELANIN...ALSO...BOUND BY OCULAR MELANIN BOTH IN VIVO & IN VITRO.|AFTER HUMAN ORAL DOSE 75 MG DOXEPIN-HCL, EST 1ST-PASS METAB RANGED FROM 55-87% OF ORAL DOSE ASSUMING COMPLETE ABSORPTION.|The pharmacokinetics of doxepin have not been extensively studied, but the drug is well absorbed from the GI tract in animals. Peak plasma concentrations occur within 2 hours after oral administration of the drug.|Limited data indicate that doxepin and its active N-demethylated metabolite are distributed into milk in concentrations reportedly ranging from about 30-140% and 10-115%, respectively, of those in maternal serum and that substantial concentrations of the active metabolite have been detected in the serum and urine of nursing infants whose mothers were receiving 75-150 mg daily.

AFTER ORAL DOSING OF DOXEPIN-HCL TO HUMANS, METABOLITE DESMETHYLDOXEPIN WAS PRODUCED.

AFTER ORAL 75 MG DOXEPIN-HCL TO HUMANS, PEAK PLASMA CONCN 8.8-45.8 NG/ML, REACHED WITHIN 4 HR. DISAPPEARANCE OF DOXEPIN WAS BIPHASIC & FOLLOWED 1ST-ORDER KINETICS. MEAN DOXEPIN T/2 WAS 16.8 HR. MEAN APPARENT VOL OF DISTRIBUTION WAS 20.2 L/KG.

ACTION OF TRICYCLIC ANTIDEPRESSANTS ON CATECHOLAMINES & INDOLEAMINES IN BRAIN...BLOCK RE-UPTAKE OF NOREPINEPHRINE BY ADRENERGIC NERVE TERMINALS. /TRICYCLIC ANTIDEPRESSANTS/

PHYSOSTIGMINE SALICYLATE, 2 MG IV, RAPIDLY REVERSED TOXIC EFFECTS OF DOXEPIN OVERDOSE (APPROX 600 MG) IN 34-YR-OLD MALE.|PATIENTS POISONED WITH 2.5 G DOXEPIN SUCCESSFULLY TREATED WITH CHARCOAL HEMOPERFUSION, WITH AMBERLITE XAD-4 RESIN FOR 6 HR.

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.

Apo Doxepin

THIN-LAYER CHROMATOGRAPHY OF DOXEPIN

DETERMINATION OF DOXEPIN IN BLOOD, URINE, OR TISSUE BY GAS CHROMATOGRAPHY, WITH CONFIRMATION BY THIN-LAYER CHROMATOGRAPHY & UV SPECTROPHOTOMETRY.|GLC METHOD FOR DETERMINATION OF DOXEPIN HCL CIS- & TRANS-ISOMERS IN HUMAN PLASMA.

Human Drugs -> FDA Approved Drug Products with Therapeutic Equivalence Evaluations (Orange Book) -> Active Ingredients