Doxepin Hydrochloride - Doxepin Hydrochloride capsule prescribing information
Suicidality and Antidepressant Drugs
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. Anyone considering the use of doxepin hydrochloride or any other antidepressant in a child, adolescent, or young adult must balance this risk with the clinical need. Short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond age 24; there was a reduction in risk with antidepressants compared to placebo in adults aged 65 and older.Depression and certain other psychiatric disorders are themselves associated with increases in the risk of suicide. Patients of all ages who are started on antidepressant therapy should be monitored appropriately and observed closely for clinical worsening, suicidality, or unusual changes in behavior. Families and caregivers should be advised of the need for close observation and communication with the prescriber. Doxepin Hydrochloride is not approved for use in pediatric patients. (See WARNINGS : Clinical Worsening and Suicide Risk , PRECAUTIONS : Information for Patients , and PRECAUTIONS : Pediatric Use ).
INDICATIONS AND USAGE
Doxepin Hydrochloride is recommended for the treatment of:
- Psychoneurotic patients with depression and/or anxiety.
- Depression and/or anxiety associated with alcoholism (not to be taken concomitantly with alcohol).
- Depression and/or anxiety associated with organic disease (the possibility of drug interaction should be considered if the patient is receiving other drugs concomitantly).
- Psychotic depressive disorders with associated anxiety including involutional depression and manic-depressive disorders.
The target symptoms of psychoneurosis that respond particularly well to doxepin hydrochloride include anxiety, tension, depression, somatic symptoms and concerns, sleep disturbances, guilt, lack of energy, fear, apprehension and worry.
Clinical experience has shown that doxepin hydrochloride is safe and well tolerated even in the elderly patient. Owing to lack of clinical experience in the pediatric population, doxepin hydrochloride is not recommended for use in children under 12 years of age.
DOSAGE AND ADMINISTRATION
For most patients with illness of mild to moderate severity, a starting daily dose of 75 mg is recommended. Dosage may subsequently be increased or decreased at appropriate intervals and according to individual response. The usual optimum dose range is 75 mg/day to 150 mg/day.
In more severely ill patients higher doses may be required with subsequent gradual increase to 300 mg/day if necessary. Additional therapeutic effect is rarely to be obtained by exceeding a dose of 300 mg/day.
In patients with very mild symptomatology or emotional symptoms accompanying organic disease, lower doses may suffice. Some of these patients have been controlled on doses as low as 25 to 50 mg/day.
The total daily dosage of doxepin hydrochloride may be given on a divided or once-a-day dosage schedule. If the once a day schedule is employed, the maximum recommended dose is 150 mg/day. This dose may be given at bedtime. The 150 mg capsule strength is intended for maintenance therapy only and is not recommended for initiation of treatment. Antianxiety effect is apparent before the antidepressant effect. Optimal antidepressant effect may not be evident for 2 to 3 weeks.
CONTRAINDICATIONS
Doxepin Hydrochloride is contraindicated in individuals who have shown hypersensitivity to the drug. Possibility of cross sensitivity with other dibenzoxepines should be kept in mind.
Doxepin Hydrochloride is contraindicated in patients with glaucoma or a tendency to urinary retention. These disorders should be ruled out, particularly in older patients.
ADVERSE REACTIONS
NOTE: Some of the adverse reactions noted below have not been specifically reported with doxepin hydrochloride use. However, due to the close pharmacological similarities among the tricyclics, the reactions should be considered when prescribing doxepin hydrochloride.
Anticholinergic Effects
Dry mouth, blurred vision, constipation, and urinary retention have been reported. If they do not subside with continued therapy, or become severe, it may be necessary to reduce the dosage.
Central Nervous System Effects
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
Cardiovascular effects including hypotension, hypertension, and tachycardia have been reported occasionally.
Allergic
Skin rash, edema, photosensitization, and pruritus have occasionally occurred.
Hematologic
Eosinophilia has been reported in a few patients. There have been occasional reports of bone marrow depression manifesting as agranulocytosis, leukopenia, thrombocytopenia, and purpura.
Gastrointestinal
Nausea, vomiting, indigestion, taste disturbances, diarrhea, anorexia, and aphthous stomatitis have been reported. (See Anticholinergic Effects .)
Endocrine
Raised or lowered 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 have been reported with tricyclic administration.
Other
Dizziness, tinnitus, weight gain, sweating, chills, fatigue, weakness, flushing, jaundice, alopecia, headache, exacerbation of asthma, angle closure glaucoma, mydriasis and hyperpyrexia (in association with chlorpromazine) have been occasionally observed as adverse effects.
The possibility of development of withdrawal symptoms upon abrupt cessation of treatment after prolonged doxepin hydrochloride administration should be borne in mind. These are not indicative of addiction and gradual withdrawal of medication should not cause these symptoms.
DESCRIPTION
Doxepin Hydrochloride, USP is one of a class of psychotherapeutic agents known as dibenzoxepin tricyclic compounds. The molecular formula of the compound is C19H21NO∙HCl having a molecular weight of 315.8. It is a white or almost white crystalline powder freely soluble in Water, Ethyl Alcohol (96%) and Dichlormethane. it may be represented by the following structural formula:
Chemically, doxepin hydrochloride, USP is a dibenzoxepin derivative and is the first of a family of tricyclic psychotherapeutic agents. Specifically, it is an isomeric mixture of: 1-Propanamine, 3-dibenz[b,e]oxepin-11 (6H)ylidene-N,N-dimethyl-hydrochloride.
Each 10 mg, 25 mg, 50 mg, 75 mg and 100 mg doxepin capsule for oral administration contains doxepin hydrochloride, USP equivalent to 10 mg, 25 mg, 50 mg, 75 mg and 100 mg of doxepin, respectively and the following inactive ingredients: Corn Starch, Dehydrate Alcohol, Dibasic Calcium Phosphate Dihydrate, Magnesium Stearate, Microcrystalline Cellulose, Silicon Dioxide, Sodium Lauryl Sulfate. The empty gelatin capsule shells contain gelatin and titanium dioxide. In addition, the 25 mg and 50 mg empty gelatin capsule shells contain FD&C Yellow No. 6 and D&C Yellow No. 10, the 75 mg and 100 mg empty gelatin capsule shells contain FD&C Green No. 3 and D&C Yellow No. 10.
The imprinting ink contains Black iron oxide, Butyl Alcohol, Dehydrated Alcohol, Isopropyl Alcohol, Potassium Hydroxide, Propylene Glycol, Purified Water, Shellac and Strong Ammonia Solution.
CLINCAL PHARMACOLOGY
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. Animal studies suggest that doxepin hydrochloride does not appreciably antagonize the antihypertensive action of guanethidine. In animal studies anticholinergic, antiserotonin and antihistamine effects on smooth muscle have been demonstrated. At higher than usual clinical doses, norepinephrine response was potentiated in animals. This effect was not demonstrated in humans.
At clinical dosages up to 150 mg per day, doxepin hydrochloride can be given to man concomitantly with guanethidine and related compounds without blocking the antihypertensive effect. At dosages above 150 mg per day blocking of the antihypertensive effect of these compounds has been reported.
Doxepin Hydrochloride is virtually devoid of euphoria as a side effect. Characteristic of this type of compound, doxepin hydrochloride has not been demonstrated to produce the physical tolerance or psychological dependence associated with addictive compounds.
HOW SUPPLIED
Doxepin Hydrochloride Capsule USP are available containing doxepin hydrochloride, USP equivalent to 10 mg, 25mg, 50mg, 75mg or 100 mg of doxepin.
The 10 mg capsule is a Hard Gelatin Capsule Shell with Opaque white cap imprinted in black with LP 158 and opaque white body imprinted in black with LP 158.They are available as follows: NDC 69315-158-01 bottles of 100 capsules
NDC 69315-158-10 bottles of 1000 capsules
The 25 mg capsule is a Hard Gelatin Capsule Shell with Opaque ivory cap imprinted in black with LP 159 and opaque white body imprinted in black with LP 159. They are available as follows: NDC 69315-159-01 bottles of 100 capsules
NDC 69315-159-10 bottles of 1000 capsules
The 50 mg capsule is a Hard Gelatin Capsule Shell with Opaque ivory cap imprinted in black with LP 160 and Opaque ivory body imprinted in black with LP 160. They are available as follows: NDC 69315-160-01 bottles of 100 capsules
NDC 69315-160-10 bottles of 1000 capsules
The 75 mg capsule is a Hard Gelatin Capsule Shell with Opaque bright light green cap imprinted in black with LP 161 and Opaque bright light green body imprinted in black with LP 161. They are available as follows: NDC 69315-161-01 bottles of 100 capsules
NDC 69315-161-10 bottles of 1000 capsules
The 100 mg capsule is a Hard Gelatin Capsule Shell- Opaque bright light green cap imprinted in black with LP 162 and opaque white body imprinted in black with LP 162. They are available as follows: NDC 69315-162-01 bottles of 100 capsules
NDC 69315-162-10 bottles of 1000 capsules
Store at 20° to 25°C (68° to 77°F). [See USP Controlled Room Temperature] Protect from light.
Dispense in a tight, light-resistant container as defined in the USP using a well-closed closure.
PHARMACIST: Dispense the accompanying Medication Guide to each patient.
Rx only
Manufactured by: LIFEPharma FZE Near Round-About 13, Plot No MO0502, Dubai, P.O. Box 17404, United Arab Emirates (ARE).
Distributed by: Leading Pharma LLC, Fairfield, NJ-07004
Rev.02 12/21
