Prudoxin

INDICATIONS AND USAGE PRUDOXIN ® Cream is indicated for the short-term (up to 8 days) management of moderate pruritus in adult patients with atopic dermatitis or lichen simplex chronicus.

DOSAGE AND ADMINISTRATION 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 eight days may result in higher systemic levels and should be avoided.

Use of PRUDOXIN ® Cream for longer than 8 days may result in an increased likelihood of contact sensitization. The risk for sedation may increase with greater body surface area application of PRUDOXIN ® Cream . 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 should not be utilized with PRUDOXIN ® Cream.

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 about the possibility of sedation and cautioned against driving a motor vehicle or operating hazardous machinery while being treated with PRUDOXIN ® Cream. The sedating effects of alcoholic beverages, antihistamines, and other CNS depressants may be potentiated when PRUDOXIN ® Cream is used.

If excessive drowsiness occurs it may be necessary to reduce the frequency of applications, the amount of cream applied, and/or the percentage of body surface area treated, or discontinue the drug. However, the efficacy with reduced frequency of applications has not been established. Keep this product away from the eyes.

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.

Pregnancy Reproduction studies have been performed in which doxepin was orally administered to rats and rabbits at doses up to 0.6 and 1.2 times, respectively, the estimated exposure to doxepin that results from use of 16 grams of PRUDOXIN ® Cream per day (four applications of four grams of cream per day; dose multiples reflect comparisons made following normalization of the data on the basis of body surface area estimates) and have revealed no evidence of harm to rat or rabbit fetuses 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. It is possible that doxepin may also be excreted in human milk following topical application of PRUDOXIN ® Cream. 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.

Controlled Clinical Trials Systemic Adverse Effects: In controlled clinical trials of patients treated with PRUDOXIN ® Cream, the most common systemic adverse event reported was drowsiness. Drowsiness occurred in 71 of 330 (22%) of patients treated with PRUDOXIN ® Cream compared to 7 of 334 (2%) of patients treated with vehicle cream. Drowsiness resulted in the premature discontinuation of the drug in approximately 5% of patients treated with PRUDOXIN ® Cream in controlled clinical trials.

Local Site Adverse Effects: In controlled clinical trials of patients treated with PRUDOXIN ® Cream, the most common local site adverse event reported was burning and/or stinging at the site of application. These occurred in 76 of 330 (23%) of patients treated with PRUDOXIN ® Cream compared to 54 of 334 (16%) of patients treated with vehicle cream. 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. The table below presents the adverse events reported at an incidence of ≥ 1 % in either PRUDOXIN ® or vehicle cream treatment groups during the trials: Adverse Event PRUDOXIN ® N=330 Vehicle N=334 Burning /Stinging 76 (23.0%) 54 (16.2%) Drowsiness 71 (21.5%) 7 (2.1%) Dry Mouth 1 32 (9.7%) 4 (1.2%) Pruritus 2 13 (3.9%) 20 (6.0%) Fatigue/Tiredness 10 (3.0%) 5 (1.5%) Exacerbated Eczema 10 (3.0%) 8 (2.4%) Other Application Site Reaction 3 10 (3.0%) 16 (4.8%) Dizziness 4 7 (2.1%) 3 (0.9%) Mental/Emotional Changes 6 (1.8%) 1 (0.3%) Taste Perversion 5 5 (1.5%) 1 (0.3%) Edema 4 (1.2%) 1 (0.3%) Headache 3 (0.9%) 14 (4.2%) 1 Includes reports of “dry lips”, “dry throat”, and “thirst” 2 Includes reports of “pruritus exacerbated” 3 Includes report of “increased irritation at application site” 4 Includes reports of “lightheadedness” and “dizziness/vertigo” 5 Includes reports of “bitter taste” and “metallic taste in mouth” Adverse events occurring in 0.5% to < 1.0% of PRUDOXIN ® Cream treated patients in the controlled clinical trials included: nervousness/anxiety, tongue numbness, fever, and nausea.