PRUDOXIN Cream (doxepin hydrochloride cream) is a topical antipuritic cream. Each gram contains: 50 mg of doxepin hydrochloride (equivalent to 44.3 mg of doxepin). Doxepin hydrochloride is one of a class of agents known as dibenzoxepin tricyclic compounds. It is an isomeric mixture of N,N-Dimethyldibenz [ b,e ] oxepin-(DELTA) 11,6H,(gamma) -propylamine hydrochloride. Doxepin hydrochloride has an empirical formula of C 19 H 21 NO·HCl and a molecular weight of 316. The base is a cream of pH 3.5 to 5.5 that includes the inactive ingredients: sorbitol, cetyl alcohol, isopropyl myristate, glyceryl stearate, PEG-100 stearate, petrolatum, benzyl alcohol, titanium dioxide and purified water.
The exact mechanism by which doxepin exerts its antipuritic effect is unknown. Doxepin HCl does have potent H1 and potent H2 receptor blocking actions. Histamine-blocking drugs appear to compete at histamine receptor sites and inhibit the biological activation of histamine receptors. In addition, doxepin produces drowsiness in significant numbers of patients. Sedation may have an effect on certain pruritic symptoms. In 19 pruritic eczema patients treated with Doxepin HCl Cream 5%, plasma doxepin concentrations ranged from nondetectable to 47 ng/mL from percutaneous absorption. Target therapeutic plasma levels of ORAL doxepin HCl for the treatment of depression range from 30 to 150 ng/mL. Once absorbed into the systemic circulation, doxepin undergoes hepatic metabolism that results in conversion to pharmacologically-active desmethyldoxepin. Further glucuronidation results in urinary excretion of the parent drug and its metabolites. Desmethyldoxepin has a half life reportedly that ranges from 28 to 52 hours and is not affected by multiple dosing. Plasma levels of both doxepin and desmethyldoxepin are highly variable and are poorly correlated with dosage. Wide distribution occurs in body tissues including lungs, heart, brain, and liver. Renal disease, genetic factors, age, and other medications affect the metabolism and subsequent elimination of doxepin. (See PRECAUTIONS : Drug Interactions .)
PRUDOXIN 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 .)
Because doxepin HCl has an anticholinergic effect and because significant plasma levels of doxepin are detectable after topical PRUDOXIN Cream application, the use of PRUDOXIN Cream is contraindicated in patients with untreated narrow angle glaucoma or a tendency to urinary retention.
PRUDOXIN Cream is contraindicated in individuals who have shown previous sensitivity to any of its components.
Drowsiness occurs in over 20% of patients treated with PRUDOXIN Cream, 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 Cream. Patients should also be warned that the effects of alcoholic beverages can be potentiated when using PRUDOXIN 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.
Drug Interactions: Studies have not been performed examining drug interactions with PRUDOXIN 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 Cream, it would not be unexpected for the following drug interactions to be possible following topical PRUDOXIN 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 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 steady-state serum tricyclic antidepressant levels and compromise their therapeutic effects.
Alcohol: Alcohol ingestion may exacerbate the potential sedative effects of PRUDOXIN Cream.
Drugs Metabolized by P 450 IID6: A subset (3% to 10%) of the population has reduced activity of certain drug metabolizing enzymes such as the cytochrome P 450 isozyme P 450 IID6. 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 interaction.
Concomitant use of tricyclic antidepressants with other drugs metabolized by cytochrome P 450 IID6 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 IC antiarrhythmics (e.g., propafenone, flecainide and encainide), or that inhibit this enzyme (e.g., quinidine), should be approached with caution. Concomitant use of PRUDOXIN Cream with drugs metabolized by cytochrome P 450 IID6 has not been formally studied.
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 HCl.
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 Cream in children have not been established.
Systemic Adverse Effects: In controlled clinical trials of patients treated with PRUDOXIN Cream, the most common systemic adverse effect reported was drowsiness. Drowsiness occurred in 22% of patients treated with PRUDOXIN Cream (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 PRUDOXIN Cream, 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 PRUDOXIN Cream 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.
PRUDOXIN Cream has been associated with allergic contact dermatitis.
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.
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 HCl 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 HCl. 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 HCl.
A thin film of PRUDOXIN 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 Cream when used for greater than 8 days. Chronic use beyond 8 days may result in higher systemic levels.
Clinical experience has shown that drowsiness is significantly more common in patients applying PRUDOXIN 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 Cream should not be utilized.
PRUDOXIN Cream is available in a 45 g (NDC 0064-3600-45) aluminum tube. Store at or below 27°C (80°F).
Rx ONLY
Distributed by:
HEALTHPOINT®
Healthpoint, Ltd.
San Antonio, Texas 78215
1-800-441-8227
Manufactured by:
DPT Laboratories, Ltd.
San Antonio, Texas 78215
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