Doxepin

Brand names: DOXEPIN HCL, DOXEPIN HYDROCHLORIDE, Doxepin Hydrochloride, Doxepin hydrochloride, Silenor, doxepin hydrochloride, Doxepin, DOXEPIN, doxepin

Warnings

BOXED WARNING: "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," while "short-term studies did not show an increase in the risk of suicidality with antidepressants compared to placebo in adults beyond age 24"; "Doxepin is not approved for use in pediatric patients." Other key warnings cover monitoring for "clinical worsening, suicidality and unusual changes in behavior," angle-closure glaucoma risk from pupillary dilation, and caution with CYP2D6-inhibiting drugs.

Contraindications

4 CONTRAINDICATIONS Hypersensitivity to doxepin hydrochloride, inactive ingredients, or other dibenzoxepines. ( 4.1 ) Co-administration with Monoamine Oxidase Inhibitors (MAOIs): Do not administer if patient is taking MAOIs or has used MAOIs within the past two weeks. ( 4.2 ) Untreated narrow angle glaucoma or severe urinary retention. ( 4.3 ) 4.1 Hypersensitivity Doxepin tablets is contraindicated in individuals who have shown hypersensitivity to doxepin HCl, any of its inactive ingredients, or other dibenzoxepines. 4.2 Co-administration with Monoamine Oxidase Inhibitors (MAOIs) Serious side effects and even death have been reported following the concomitant use of certain drugs with MAO inhibitors. Do not administer Doxepin tablets if patient is currently on MAOIs or has used MAOIs within the past two weeks. The exact length of time may vary depending on the particular MAOI dosage and duration of treatment. 4.3 Glaucoma and Urinary Retention Doxepin tablets is contraindicated in individuals with untreated narrow angle glaucoma or severe urinary retention.

Overdose

10 OVERDOSAGE Doxepin is routinely administered for indications other than insomnia at doses 10- to 50-fold higher than the highest recommended dose of Doxepin tablets. The signs and symptoms associated with doxepin use at doses several-fold higher than the maximum recommended dose (Excessive dose) of Doxepin tablets for the treatment of insomnia are described [see Overdosage (10.1) ] , as are signs and symptoms associated with higher multiples of the maximum recommended dose (Critical overdose) [see Overdosage (10.2) ] . 10.1 Signs and Symptoms of Excessive Doses The following adverse effects have been associated with use of doxepin at doses higher than 6 mg. Anticholinergic Effects: constipation and urinary retention. Central Nervous System: disorientation, hallucinations, numbness, paresthesias, extrapyramidal symptoms, seizures, tardive dyskinesia. Cardiovascular: hypotension. Gastrointestinal: aphthous stomatitis, indigestion. Endocrine: raised 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. Other: tinnitus, weight gain, sweating, flushing, jaundice, alopecia, exacerbation of asthma, and hyperpyrexia (in association with chlorpromazine). 10.2 Signs and Symptoms of Critical Overdose Manifestations of doxepin critical overdose include: cardiac dysrhythmias, severe hypotension, convulsions, and CNS depression including coma. Electrocardiogram changes, particularly in QRS axis or width, are clinically significant indicators of tricyclic compound toxicity. Other signs of overdose may include, but are not limited to: confusion, disturbed concentration, transient visual hallucinations, dilated pupils, agitation, hyperactive reflexes, stupor, drowsiness, muscle rigidity, vomiting, hypothermia, hyperpyrexia. 10.3 Recommended Management As management of overdose is complex and changing, it is recommended that the physician contact a poison control center for current information on treatment. In addition, the possibility of a multiple drug ingestion should be considered. If an overdose is suspected, an ECG should be obtained and cardiac monitoring should be initiated immediately. The patient’s airway should be protected, an intravenous line should be established, and gastric decontamination should be initiated. 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 overdose should receive gastrointestinal decontamination. This should include large volume gastric lavage followed by administration of 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 ≥0.10 seconds may be the best indication of the severity of an overdose. Serum alkalinization, using intravenous sodium bicarbonate should be used to maintain the serum pH in the range of 7.45 to 7.55 for patients with dysrhythmias and/or QRS widening. 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 >7.60 or a pCO 2 <20 mm Hg is undesirable. Dysrhythmias unresponsive to sodium bicarbonate therapy/hyperventilation may respond to lidocaine 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 treatment of tricyclic compound poisoning. Central Nervous System In patients with central nervous system 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 or 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 overdose often is 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 overdoses are similar. It is strongly recommended that the physician contact the local poison control center for specific pediatric treatment.

Drug interactions

7 DRUG INTERACTIONS MAO inhibitors: Doxepin tablets should not be administered in patients on MAOIs within the past two weeks. ( 4.2 ) Cimetidine: Increases exposure to doxepin. ( 7.2 ) Alcohol: Sedative effects may be increased with doxepin. ( 7.3 , 5.4 ) CNS Depressants and Sedating Antihistamines: Sedative effects may be increased with doxepin. ( 7.4 , 5.4 ) Tolazamide: A case of severe hypoglycemia has been reported. ( 7.5 ) 7.1 Cytochrome P450 Isozymes Doxepin tablets is primarily metabolized by hepatic cytochrome P450 isozymes CYP2C19 and CYP2D6, and to a lesser extent, by CYP1A2 and CYP2C9. Inhibitors of these isozymes may increase the exposure of doxepin. Doxepin tablets is not an inhibitor of any CYP isozymes at therapeutically relevant concentrations. The ability of Doxepin tablets to induce CYP isozymes is not known. 7.2 Cimetidine Doxepin tablets exposure is doubled with concomitant administration of cimetidine, a nonspecific inhibitor of CYP isozymes. A maximum dose of 3 mg is recommended in adults and elderly when cimetidine is co-administered with Doxepin tablets [see Clinical Pharmacology (12.3) ] 7.3 Alcohol When taken with Doxepin tablets, the sedative effects of alcohol may be potentiated [ see Warnings and Precautions (5.2 , 5.4) ] . 7.4 CNS Depressants and Sedating Antihistamines When taken with Doxepin tablets, the sedative effects of sedating antihistamines and CNS depressants may be potentiated [ see Warnings and Precautions (5.2 , 5.4) ] . 7.5 Tolazamide A case of severe hypoglycemia has been reported in a type II diabetic patient maintained on tolazamide (1 g/day) 11 days after the addition of oral doxepin (75 mg/day).

Uses

Indicated for "psychoneurotic patients with depression and/or anxiety," depression and/or anxiety "associated with alcoholism," "associated with organic disease," and "psychotic depressive disorders with associated anxiety," targeting symptoms such as "anxiety, tension, depression, somatic symptoms and concerns, sleep disturbances, guilt, lack of energy, fear, apprehension and worry."

Dosage forms & strengths

Capsule Tablet Tablet, Film Coated TABLET, FILM COATED TABLET

DOXEPIN HYDROCHLORIDE 10 mg DOXEPIN HYDROCHLORIDE 100 mg DOXEPIN HYDROCHLORIDE 150 mg DOXEPIN HYDROCHLORIDE 25 mg DOXEPIN HYDROCHLORIDE 3 mg DOXEPIN HYDROCHLORIDE 50 mg DOXEPIN HYDROCHLORIDE 6 mg DOXEPIN HYDROCHLORIDE 75 mg Doxepin Hydrochloride 10 mg Doxepin Hydrochloride 100 mg Doxepin Hydrochloride 25 mg Doxepin Hydrochloride 50 mg Doxepin Hydrochloride 75 mg doxepin hydrochloride 3 mg doxepin hydrochloride 6 mg DOXEPIN HYDROCHLORIDE 3 mg/1 DOXEPIN HYDROCHLORIDE 6 mg/1

2 DOSAGE AND ADMINISTRATION The dose of Doxepin tablets should be individualized. Initial dose: 6 mg, once daily for adults ( 2.1 ) and 3 mg, once daily for the elderly. ( 2.1 , 2.2 ) Take within 30 minutes of bedtime. Total daily dose should not exceed 6 mg. ( 2.3 ) Should not be taken within 3 hours of a meal. ( 2.3 , 12.3 ) 2.1 Dosing in Adults The recommended dose of Doxepin tablets for adults is 6 mg once daily. A 3 mg once daily dose may be appropriate for some patients, if clinically indicated. 2.2 Dosing in the Elderly The recommended starting dose of Doxepin tablets in elderly patients (≥ 65 years old) is 3 mg once daily. The daily dose can be increased to 6 mg, if clinically indicated. 2.3 Administration Doxepin tablets should be taken within 30 minutes of bedtime. To minimize the potential for next day effects, Doxepin tablets should not be taken within 3 hours of a meal [ see Clinical Pharmacology (12.3) ] . The total Doxepin tablets dose should not exceed 6 mg per day.

All identified pills

3 SP

BLUE OVAL · Doxepin

2 manufacturers