Prudoxin

PRUDOXIN (doxepin) Cream is available in a 45 g (NDC 0064-3600-45) aluminum tube. Store at or below 27° C (80° F).

HEALTH POINT® 1-800-441-8227. www.healthpoint.com. FDA Rev date: n/a

PRUDOXIN (doxepin) Cream is indicated for the short-term (up to 8 days) management of moderate pruritus in adult patients with the following forms of eczematous dermatitis: atopic dermatitis and lichen simplex chronicus. (See DOSAGE AND ADMINISTRATION.)

A thin film of PRUDOXIN (doxepin) Cream should be applied four times each day with at least a 3 to 4 hour interval between applications. There are no data to establish the safety and effectiveness of PRUDOXIN (doxepin) Cream when used for greater than eight days. Chronic use beyond eight days may result in higher systemic levels.

Clinical experience has shown that drowsiness is significantly more common in patients applying PRUDOXIN (doxepin) Cream to over 10% of body surface area; therefore, patients with greater than 10% of body surface area affected should be particularly cautioned concerning possible drowsiness and other systemic adverse effects of doxepin. If excessive drowsiness occurs it may be necessary to do one or more of the following: reduce the body surface area treated, reduce the number of applications per day, reduce the amount of cream applied, or discontinue the drug.

Occlusive dressings may increase the absorption of most topical drugs; therefore, occlusive dressings with PRUDOXIN (doxepin) Cream should not be utilized.

Because doxepin HCI has an anticholinergic effect and because significant plasma levels of doxepin are detectable after topical PRUDOXIN (doxepin) Cream application, the use of PRUDOXIN (doxepin) Cream is contraindicated in patients with untreated narrow angle glaucoma or a tendency to urinary retention.

PRUDOXIN (doxepin) Cream is contraindicated in individuals who have shown previous sensitivity to any of its components.

WARNINGS

Drowsiness occurs in over 20% of patients treated with Doxepin HCl Cream 5%, especially in patients receiving treatment to greater than 10% of their body surface area. Patients should be warned of this possibility and cautioned against driving a motor vehicle or operating hazardous machinery while being treated with PRUDOXIN (doxepin) Cream. Patients should also be warned that the effects of alcoholic beverages can be potentiated when using PRUDOXIN (doxepin) Cream. If excessive drowsiness occurs it may be necessary to reduce the number of applications, the amount of cream applied, and/or the percentage of body surface area treated, or discontinue the drug.

Keep this product away from the eyes.

PRECAUTIONS

Carcinogenesis, Mutagenesis, Impairment of Fertility

Carcinogenesis, mutagenesis, impairment of fertility studies have not been conducted with doxepin hydrochloride.

Pregnancy

Pregnancy Category B: Teratology studies have been performed in rats and rabbits at oral doses up to 8 times the topical human dose (based on a mg/kg basis) and have revealed no evidence of impaired fertility or harm to the fetus due to doxepin. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

Nursing Mothers

Doxepin is excreted in human milk after oral administration. There have been no studies conducted to date to determine if doxepin is excreted in human milk after topical administration; however, it is known that significant systemic levels of doxepin are obtained after topical administration. It is therefore possible that doxepin could be secreted in human milk following topical administration.

One case has been reported of apnea and drowsiness in a nursing infant whose mother was taking an oral dosage form of doxepin HCI.

Because of the potential for serious adverse reactions in nursing infants from doxepin, a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother.

Pediatric Use

Safety and effectiveness of PRUDOXIN (doxepin) Cream in children have not been established.

SIDE EFFECTS

Controlled Clinical Trials

Systemic Adverse Effects: In controlled clinical trials of patients treated with Doxepin HCl Cream 5%, the most common systemic adverse effect reported was drowsiness. Drowsiness occurred in 22% of patients treated with Doxepin HCl Cream 5% (and 2% of patients treated with placebo cream) and resulted in the premature discontinuation of the drug in approximately 5% of patients treated.

Other systemic adverse effects reported in approximately 1 to 10% of these patients included: Dry mouth, dry lips, thirst, headache, fatigue, dizziness, emotional changes, and taste changes.

Other systemic adverse effects reported in less than 1% of these patients included: Nausea, anxiety and fever.

Local Site Adverse Effects: In controlled clinical trials of patients treated with Doxepin HCl Cream 5%, the most common local site adverse effect reported was burning and/or stinging at the site of application. These occurred in approximately 21% of these patients. Most of these reactions were categorized as "mild"; however, approximately 25% of patients who reported burning and/or stinging reported the reaction as "severe". Four patients treated with Doxepin HCl Cream 5% withdrew from the study because of the burning and/or stinging.

Other local site adverse effects reported in approximately 1 to 10% of these patients included: Pruritus exacerbation, eczema exacerbation, dryness and tightness to skin, paresthesias, and edema.

Other local site adverse effects reported in less than 1% of these patients included: Irritation, tingling, scaling, and cracking.

Post Marketing Experience

Some cases of allergic contact dermatitis have been reported in patients using Doxepin HCl 5% cream.

DRUG INTERACTIONS

Studies have not been performed examining drug interactions with PRUDOXIN (doxepin) Cream. However, data are available regarding potentially significant drug interactions regarding doxepin. As plasma levels of doxepin similar to therapeutic ranges for antidepressant therapy can be obtained following topical application of PRUDOXIN (doxepin) Cream, it would not be unexpected for the following drug interactions to be possible following topical PRUDOXIN (doxepin) Cream application.

MAO Inhibitors: Serious side effects and even death have been reported following the concomitant use of certain orally administered drugs chemically related to doxepin and MAO inhibitors. Therefore, MAO inhibitors should be discontinued at least two weeks prior to the initiation of treatment with PRUDOXIN (doxepin) Cream.

Cimetidine: Cimetidine has been reported to produce clinically significant fluctuations in steady-state serum concentrations of various tricyclic antidepressants. Serious anticholinergic symptoms have been associated with elevations in the serum levels of tricyclic antidepressants when cimetidine therapy is initiated. Additionally, higher than expected tricyclic antidepressant levels have been observed 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: Alcohol ingestion may exacerbate the potential sedative effects of PRUDOXIN (doxepin) Cream.

Drugs Metabolized by P₄₅₀IID6: A subset (3% to 10%) of the population has reduced activity of certain drug metabolizing enzymes such as the cytochrome P₄₅₀ isozyme P₄₅₀IID6. Such individuals are referred to as "poor metabolizers" of drugs such as debrisoquin, dextromethorphan, and the tricyclic antidepressants. These individuals may have higher than expected plasma concentrations of tricyclic antidepressant when given usual doses. In addition, certain drugs that are metabolized by this isozyme, including many antidepressants (tricyclic antidepressants, selective serotonin reuptake inhibitors, and others), may inhibit the activity of this isozyme, and thus may make normal metabolizers resemble poor metabolizers with regard to concomitant therapy with other drugs metabolized by this enzyme system, leading to drug interactions.

Concomitant use of tricyclic antidepressants with other drugs metabolized by cytochrome P₄₅₀IID6 may require lower doses than usually prescribed for either the tricyclic antidepressant or the other drug. Therefore, co-administration of tricyclic antidepressants with other drugs that are metabolized by this isoenzyme, including other antidepressants, phenothiazines, carbamazepine, and Type 1C antiarrhythmics (e.g., propafenone, flecainide and encainide), or that inhibit this enzyme (e.g., quinidine), should be approached with caution. Concomitant use of PRUDOXIN (doxepin) Cream with drugs metabolized by cytochrome P₄₅₀IID6 has not been formally studied.

Pregnancy Category B: Teratology studies have been performed in rats and rabbits at oral doses up to 8 times the topical human dose (based on a mg/kg basis) and have revealed no evidence of impaired fertility or harm to the fetus due to doxepin. There are, however, no adequate and well-controlled studies in pregnant women. Because animal reproduction studies are not always predictive of human response, this drug should be used during pregnancy only if clearly needed.

Controlled Clinical Trials

Systemic Adverse Effects: In controlled clinical trials of patients treated with Doxepin HCl Cream 5%, the most common systemic adverse effect reported was drowsiness. Drowsiness occurred in 22% of patients treated with Doxepin HCl Cream 5% (and 2% of patients treated with placebo cream) and resulted in the premature discontinuation of the drug in approximately 5% of patients treated.

Other systemic adverse effects reported in approximately 1 to 10% of these patients included: Dry mouth, dry lips, thirst, headache, fatigue, dizziness, emotional changes, and taste changes.

Other systemic adverse effects reported in less than 1% of these patients included: Nausea, anxiety and fever.

Local Site Adverse Effects: In controlled clinical trials of patients treated with Doxepin HCl Cream 5%, the most common local site adverse effect reported was burning and/or stinging at the site of application. These occurred in approximately 21% of these patients. Most of these reactions were categorized as "mild"; however, approximately 25% of patients who reported burning and/or stinging reported the reaction as "severe". Four patients treated with Doxepin HCl Cream 5% withdrew from the study because of the burning and/or stinging.

Other local site adverse effects reported in approximately 1 to 10% of these patients included: Pruritus exacerbation, eczema exacerbation, dryness and tightness to skin, paresthesias, and edema.

Other local site adverse effects reported in less than 1% of these patients included: Irritation, tingling, scaling, and cracking.

Post Marketing Experience

Some cases of allergic contact dermatitis have been reported in patients using Doxepin HCl 5% cream.

Overdosage with a topical product is unlikely; should it occur, the signs and symptoms include: Mild: Drowsiness, stupor, blurred vision, excessive dryness of mouth.

Severe:Respiratory depression, hypotension, coma, convulsions, cardiac arrhythmias and tachycardias. Also, urinary retention (bladder atony), decreased gastrointestinal motility (paralytic ileus), hyperthermia (or hypothermia), hypertension, dilated pupils, hyperactive reflexes.

Management and Treatment

Mild: Observation and supportive therapy is all that is usually necessary. It may be necessary to reduce the percent of body surface area treated or the frequency of application or apply a thinner layer of cream.

Severe: Medical management of severe doxepin overdosage consists of aggressive supportive therapy. The area covered with doxepin HCI cream should be thoroughly washed. An adequate airway should be established in comatose patients and assisted ventilation used if necessary. EKG monitoring may be required for several days, because relapse after apparent recovery has been reported with oral doxepin HCI. Arrhythmias should be treated with the appropriate antiarrhythmic agent. It has been reported that many of the cardiovascular and CNS symptoms of tricyclic antidepressant poisoning in adults may be reversed by the slow intravenous administration of 1 mg to 3 mg of physostigmine salicylate. Because physostigmine is rapidly metabolized, the dosage should be repeated as required. Convulsions may respond to standard anticonvulsant therapy; however, barbiturates may potentiate any respiratory depression. Dialysis and forced diuresis generally are not of value in the management of overdosage due to high tissue and protein binding of doxepin HCI.