Doxepin HCL

Doxepin Hydrochloride Capsules, USP are 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 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 are safe and well tolerated even in the elderly patient. Owing to lack of clinical experience in the pediatric population, doxepin hydrochloride capsules are 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 mg/day 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 hydrochloride capsules are contraindicated in individuals who have shown hypersensitivity to the drug. Possibility of cross sensitivity with other dibenzoxepines should be kept in mind. Doxepin hydrochloride capsules are 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 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. Withdrawal Symptoms: 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. To report SUSPECTED ADVERSE REACTIONS, contact Alembic Pharmaceuticals Limited at 1-866-210-9797 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.

Doxepin hydrochloride 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 315.84. It is a white to almost white crystalline powder freely soluble in water, in alcohol and methylene chloride. It may be represented by the following structural formula: [Doxepin Hydrochloride 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 (6H)ylidene-N,N-dimethyl-hydrochloride. Each 10 mg, 25 mg, 50 mg, 75 mg and 100 mg doxepin hydrochloride 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: colloidal silicon dioxide, magnesium stearate, microcrystalline cellulose, pregelatinized starch (maize), and sodium lauryl sulfate. The empty gelatin capsule shells contain D&C Yellow No. 10, gelatin, sodium lauryl sulfate and titanium dioxide. In addition, the 25 mg and 50 mg empty gelatin capsule shells contain FD&C Yellow 6, the 75 mg and 100 mg empty gelatin capsule shells contain FD&C Green 3 and the 10 mg empty gelatin capsule shells contain FD&C Red 3. The imprinting ink contains black iron oxide, butyl alcohol, dehydrated alcohol, isopropyl alcohol, potassium hydroxide, propylene glycol, purified water, shellac and strong ammonia solution. FDA approved dissolution test specifications differ from USP.

Deaths may occur from overdosage with this class of drugs. Multiple drug ingestion (including alcohol) is common in deliberate tricyclic antidepressant overdose. As the management is complex and changing, it is recommended that the physician contact a poison control center for current information on treatment. Signs and symptoms of toxicity develop rapidly after tricyclic antidepressant overdose; therefore, hospital monitoring is required as soon as possible. Manifestations: Critical manifestations of overdose include: 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. Other signs of overdose may include: confusion, disturbed concentration, transient visual hallucinations, dilated pupils, agitation, hyperactive reflexes, stupor, drowsiness, muscle rigidity, vomiting, hypothermia, hyperpyrexia, or any of the symptoms listed under ADVERSE REACTIONS. Deaths have been reported involving overdoses of doxepin. General Recommendations: General: 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. There are case reports of patients succumbing to fatal dysrhythmias late after overdose; these patients had clinical evidence of significant poisoning prior to death and most received inadequate gastrointestinal decontamination. Monitoring of plasma drug levels should not guide management of the patient. Gastrointestinal Decontamination: All patients suspected of tricyclic antidepressant overdose should receive gastrointestinal decontamination. This should include large volume gastric lavage followed by activated charcoal. If consciousness is impaired, the airway should be secured prior to lavage. Emesis is contraindicated. Cardiovascular: A maximal limb-lead QRS duration of greater than or equal to 0.10 seconds may be the best indication of the severity of the overdose. Intravenous sodium bicarbonate should be used to maintain the serum pH in the range of 7.45 to 7.55. If the pH response is inadequate, hyperventilation may also be used. Concomitant use of hyperventilation and sodium bicarbonate should be done with extreme caution, with frequent pH monitoring. A pH greater than 7.60 or a pCO2 less than 20 mm Hg is undesirable. Dysrhythmias unresponsive to sodium bicarbonate therapy/hyperventilation may respond to lidocaine, bretylium or phenytoin. Type 1A and 1C antiarrhythmics are generally contraindicated (e.g., quinidine, disopyramide, and procainamide). In rare instances, hemoperfusion may be beneficial in acute refractory cardiovascular instability in patients with acute toxicity. However, hemodialysis, peritoneal dialysis, exchange transfusions, and forced diuresis generally have been reported as ineffective in tricyclic antidepressant poisoning. CNS: In patients with CNS depression, early intubation is advised because of the potential for abrupt deterioration. Seizures should be controlled with benzodiazepines, or if these are ineffective, other anticonvulsants (e.g., phenobarbital, phenytoin). Physostigmine is not recommended except to treat life-threatening symptoms that have been unresponsive to other therapies, and then only in consultation with a poison control center. Psychiatric Follow-up: Since overdosage is often deliberate, patients may attempt suicide by other means during the recovery phase. Psychiatric referral may be appropriate. Pediatric Management: The principles of management of child and adult overdosages are similar. It is str …

Doxepin Hydrochloride Capsules, USP are available containing doxepin hydrochloride, USP equivalent to 10 mg, 25 mg, 50 mg, 75 mg or 100 mg of doxepin. The 10 mg capsule is light yellow to yellow opaque cap / light yellow to yellow opaque body, hard gelatin capsule, imprinted with [Image] on cap and "424" on body with black ink containing white to off white powder. They are available as follows: NDC 72189-590-30 bottles of 30 capsules, with child-resistant closure NDC 70756-424-51 bottles of 500 capsules. This package is not child resistant. The 25 mg capsule is light yellow to yellow opaque cap / white to off white opaque body, hard gelatin capsule, imprinted with [Image] on cap and "425" on body with black ink containing white to off white powder. They are available as follows: NDC 70756-425-11 bottles of 100 capsules, with child-resistant closure NDC 70756-425-51 bottles of 500 capsules. This package is not child resistant. The 50 mg capsule is light yellow to yellow opaque cap and light yellow to yellow opaque body, hard gelatin capsule, imprinted with [Image] on cap and "426" on body with black ink containing white to off white powder. They are available as follows: NDC 70756-426-11 bottles of 100 capsules, with child-resistant closure NDC 70756-426-51 bottles of 500 capsules. This package is not child resistant. The 75 mg capsule is light green to green opaque cap and light green to green opaque body, hard gelatin capsule, imprinted with [Image] on cap and "427" on body with black ink containing white to off white powder. They are available as follows: NDC 70756-427-11 bottles of 100 capsules, with child-resistant closure NDC 70756-427-51 bottles of 500 capsules, This package is not child resistant. The 100 mg capsule is light green to green opaque cap and white to off white opaque body, hard gelatin capsule, imprinted with [Image] on cap and "428" on body with black ink containing white to off white powder. They are available as follows: NDC 70756-428-11 bottles of 100 capsules, with child-resistant closure NDC 70756-428-51 bottles of 500 capsules, This package is not child resistant.