Get your patient on Doxepin Hydrochloride - Doxepin Hydrochloride capsule (Doxepin Hydrochloride)

Doxepin hydrochloride capsules are recommended for the treatment of:

1. Psychoneurotic patients with depression and/or anxiety.
2. Depression and/or anxiety associated with alcoholism (not to be taken concomitantly with alcohol).
3. Depression and/or anxiety associated with organic disease (the possibility of drug interaction should be considered if the patient is receiving other drugs concomitantly).
4. 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 capsules 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 capsules is safe and well tolerated even in the elderly patient. Owing to lack of clinical experience in the pediatric population, doxepin is not recommended for use in children under 12 years of age.

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 (as the 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.

Anti-anxiety effect is apparent before the antidepressant effect. Optimal antidepressant effect may not be evident for two to three weeks.

Doxepin is contraindicated in individuals who have shown hypersensitivity to the drug. Possibility of cross sensitivity with other dibenzoxepines should be kept in mind.

Doxepin is contraindicated in patients with glaucoma or a tendency to urinary retention. These disorders should be ruled out, particularly in older patients.

NOTE: Some of the adverse reactions noted below have not been specifically reported with doxepin 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.

Withdrawal Symptoms:

The possibility of development of withdrawal symptoms upon abrupt cessation of treatment after prolonged doxepin administration should be borne in mind. These are not indicative of addiction and gradual withdrawal of medication should not cause these symptoms.

To report SUSPECTED ADVERSE REACTIONS, contact Amneal Pharmaceuticals at 1-877-835-5472 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Drugs Metabolized by P450 2D6:

The biochemical activity of the drug metabolizing isozyme cytochrome P450 2D6 (debrisoquin hydroxylase) is reduced in a subset of the Caucasian population (about 7% to 10% of Caucasians are so called "poor metabolizers"); reliable estimates of the prevalence of reduced P450 2D6 isozyme activity among Asian, African and other populations are not yet available. Poor metabolizers have higher than expected plasma concentrations of tricyclic antidepressants (TCAs) when given usual doses. Depending on the fraction of drug metabolized by P450 2D6, the increase in plasma concentration may be small, or quite large (8-fold increase in plasma AUC of the TCA).

In addition, certain drugs inhibit the activity of this isozyme and make normal metabolizers resemble poor metabolizers. An individual who is stable on a given dose of TCA may become abruptly toxic when given one of these inhibiting drugs as concomitant therapy. The drugs that inhibit cytochrome P450 2D6 include some that are not metabolized by the enzyme (quinidine; cimetidine) and many that are substrates for P450 2D6 (many other antidepressants, phenothiazines and the Type 1C antiarrhythmics propafenone and flecainide). While all the selective serotonin reuptake inhibitors (SSRIs), e.g., citalopram, escitalopram, fluoxetine, sertraline and paroxetine, inhibit P450 2D6, they may vary in the extent of inhibition. The extent to which SSRI-TCA interactions may pose clinical problems will depend on the degree of inhibition and the pharmacokinetics of the SSRI involved. Nevertheless, caution is indicated in the co-administration of TCAs with any of the SSRIs and also in switching from one class to the other. Of particular importance, sufficient time must elapse before initiating TCA treatment in a patient being withdrawn from fluoxetine, given the long half-life of the parent and active metabolite (at least 5 weeks may be necessary).

Concomitant use of tricyclic antidepressants with drugs that can inhibit cytochrome P450 2D6 may require lower doses than usually prescribed for either the tricyclic antidepressant or the other drug. Furthermore, whenever one of these other drugs is withdrawn from co-therapy, an increased dose of tricyclic antidepressant may be required. It is desirable to monitor TCA plasma levels whenever a TCA is going to be co-administered with another drug known to be an inhibitor of P450 2D6.

Doxepin is primarily metabolized by CYP2D6 (with CYP1A2 & CYP3A4 as minor pathways). Inhibitors or substrates of CYP2D6 (i.e., quinidine, selective serotonin reuptake inhibitors [SSRIs]) may increase the plasma concentration of doxepin when administered concomitantly. The extent of interaction depends on the variability of effect on CYP2D6. The clinical significance of this interaction with doxepin has not been systematically evaluated.

MAO Inhibitors:

Serious side effects and even death have been reported following the concomitant use of certain drugs with MAO inhibitors. Therefore, MAO inhibitors should be discontinued at least two weeks prior to the cautious initiation of therapy with doxepin. The exact length of time may vary and is dependent upon the particular MAO inhibitor being used, the length of time it has been administered, and the dosage involved.

Cimetidine:

Cimetidine has been reported to produce clinically significant fluctuations in steady-state serum concentrations of various tricyclic antidepressants. Serious anticholinergic symptoms (i.e., severe dry mouth, urinary retention and blurred vision) have been associated with elevations in the serum levels of tricyclic antidepressant when cimetidine therapy is initiated. Additionally, higher than expected tricyclic antidepressant levels have been observed when they are begun in patients already taking cimetidine. In patients who have been reported to be well controlled on tricyclic antidepressants receiving concurrent cimetidine therapy, discontinuation of cimetidine has been reported to decrease established steady-state serum tricyclic antidepressant levels and compromise their therapeutic effects.

Alcohol:

It should be borne in mind that alcohol ingestion may increase the danger inherent in any intentional or unintentional doxepin overdosage. This is especially important in patients who may use alcohol excessively.

Tolazamide:

A case of severe hypoglycemia has been reported in a type II diabetic patient maintained on tolazamide (1 gm/day) 11 days after the addition of doxepin (75 mg/day).

Drowsiness:

Since drowsiness may occur with the use of this drug, patients should be warned of the possibility and cautioned against driving a car or operating dangerous machinery while taking the drug. Patients should also be cautioned that their response to alcohol may be potentiated.

Sedating drugs may cause confusion and over sedation in the elderly; elderly patients generally should be started on low doses of doxepin and observed closely (see PRECAUTIONS : Geriatric Use ).

Suicide:

Since suicide is an inherent risk in any depressed patient and may remain so until significant improvement has occurred, patients should be closely supervised during the early course of therapy. Prescriptions should be written for the smallest feasible amount.

Psychosis:

Should increased symptoms of psychosis or shift to manic symptomatology occur, it may be necessary to reduce dosage or add a major tranquilizer to the dosage regimen.

Doxepin hydrochloride is one of a class of psychotherapeutic agents known as dibenzoxepin tricyclic compounds. The molecular formula of the compound is C ₁₉ H ₂₁ NO • HCl having a molecular weight of 316. It is a white crystalline solid readily soluble in water, lower alcohols and chloroform. It may be represented by the following structural formula:

Chemically, doxepin hydrochloride 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 (6 H )ylidene- N , N -dimethyl-hydrochloride.

Each 10 mg, 25 mg, 50 mg, 75 mg and 100 mg doxepin capsule, USP 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: colloidal silicon dioxide, magnesium stearate, microcrystalline cellulose, pregelatinized starch and sodium lauryl sulfate.

The hard gelatin capsule shells contain D&C Yellow No. 10, gelatin, sodium lauryl sulfate and titanium dioxide. In addition, the 75 mg and 100 mg hard gelatin capsule shells contain FD&C Green No. 3.

The imprinting ink contains black iron oxide, potassium hydroxide, propylene glycol, shellac and strong ammonia solution.

Meets USP Dissolution Test 2.

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 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 is virtually devoid of euphoria as a side effect. Characteristic of this type of compound, doxepin has not been demonstrated to produce the physical tolerance or psychological dependence associated with addictive compounds.

Doxepin Hydrochloride Capsules USP, 10 mg are supplied as hard gelatin capsule filled with white to off-white granular powder having “AMNEAL” printed on yellow opaque cap and “1166” printed on yellow opaque body with black ink.
They are available as follows:

Bottle of 30 Capsules:                           NDC 69238-1166-3

Bottle of 90 Capsules:                           NDC 69238-1166-9

Bottle of 1000 Capsules:                       NDC 69238-1166-1

Doxepin Hydrochloride Capsules USP, 25 mg are supplied as hard gelatin capsule filled with white to off-white granular powder having “AMNEAL” printed on yellow opaque cap and “1170” printed on white opaque body with black ink.
They are available as follows:

Bottle of 30 Capsules:                           NDC 69238-1170-3

Bottle of 90 Capsules:                           NDC 69238-1170-9

Bottle of 1000 Capsules:                       NDC 69238-1170-1

Doxepin Hydrochloride Capsules USP, 50 mg are supplied as hard gelatin capsule filled with white to off-white granular powder having “AMNEAL” printed on yellow opaque cap and “1171” printed on yellow opaque body with black ink.
They are available as follows:

Bottle of 30 Capsules:                           NDC 69238-1171-3

Bottle of 90 Capsules:                           NDC 69238-1171-9

Bottle of 1000 Capsules:                       NDC 69238-1171-1

Doxepin Hydrochloride Capsules USP, 75 mg are supplied as hard gelatin capsule filled with white to off-white granular powder having “AMNEAL” printed on green opaque cap and “1172” printed on green opaque body with black ink.
They are available as follows:

Bottle of 30 Capsules:                           NDC 69238-1172-3

Bottle of 90 Capsules:                           NDC 69238-1172-9

Bottle of 1000 Capsules:                       NDC 69238-1172-1

Doxepin Hydrochloride Capsules USP, 100 mg are supplied as hard gelatin capsule filled with white to off-white granular powder having “AMNEAL” printed on green opaque cap and “1173” printed on white opaque body with black ink.
They are available as follows:

Bottle of 30 Capsules:                           NDC 69238-1173-3

Bottle of 90 Capsules:                           NDC 69238-1173-9

Bottle of 1000 Capsules:                       NDC 69238-1173-1

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 child-resistant closure.

PHARMACIST: Dispense a Medication Guide with each prescription.

Manufactured by:
Amneal Pharmaceuticals Pvt. Ltd.
Ahmedabad 382220, INDIA

Distributed by:
Amneal Pharmaceuticals LLC
Bridgewater, NJ 08807

Rev. 08-2024-04