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Hill Dermaceuticals, Inc. 12/3/10

  

Department of Health and Human Services logoDepartment of Health and Human Services

Public Health Service
Food and Drug Administration
 

Silver Spring, MD 20993 


TRANSMITTED BY FACSIMILE


Jerry Roth
President
Hill Dermaceuticals, Inc.
2650 S. Mellonville Avenue
Sanford, Florida 32773


RE: NDA #019452
Derma-Smoothe/FS® (fluocinolone acetonide) Topical Oil, 0.01% (Body Oil)
MACMIS #19329


WARNING LETTER


Dear Mr. Roth:


The Division of Drug Marketing, Advertising, and Communications (DDMAC) has reviewed the “Pediatric Atopic Dermatitis” webpages of the Hill Dermaceuticals, Inc. (Hill Dermaceuticals) website for Derma-Smoothe/FS® (fluocinolone acetonide) Topical Oil, 0.01% (Body Oil) (Derma-Smoothe Body Oil) submitted as a complaint to the DDMAC Bad Ad Program. The webpages are false or misleading because they omit and minimize the risks associated with the use of Derma-Smoothe Body Oil, overstate its efficacy, present unsubstantiated superiority claims, broaden and inadequately communicate the indication, and present unsubstantiated claims for the drug product. Thus, the webpages misbrand the drug in violation of the Federal Food, Drug, and Cosmetic Act (the Act), 21 U.S.C. 352(a) & (n); 321(n), and FDA implementing regulations. See 21 CFR 202.1(e)(3)(i); (e)(5); (e)(6)(i) & (ii). These violations are concerning from a public health perspective because they suggest that Derma-Smoothe Body Oil is safer or more effective than has been demonstrated.


Background


According to its FDA-approved product labeling (PI), Derma-Smoothe Body Oil is “indicated for the topical treatment of moderate to severe atopic dermatitis in pediatric patients, 3 months and older for up to 4 weeks. Safety and effectiveness in pediatric patients younger than 3 months of age have not been established.”


The Indications and Usage section of the PI also includes the important limitations to apply the least amount of Derma-Smoothe Body Oil to cover the affected areas, to discontinue Derma-Smoothe Body Oil when control of disease is achieved, to contact the physician if no improvement is seen within 2 weeks, to not apply Derma-Smoothe Body Oil to the diaper area, to not use Derma-Smoothe Body Oil on the face, axillae, or groin unless directed by the physician, and to avoid application to intertriginous areas due to the increased risk of local adverse reactions.


Derma-Smoothe Body Oil is associated with warnings and precautions such as the following:


The systemic absorption of topical corticosteroids can produce reversible hypothalamic-pituitary-adrenal (HPA) axis suppression with the potential for glucocorticosteroid insufficiency. Cushing's syndrome, hyperglycemia, and glucosuria can also be produced by systemic absorption of topical corticosteroids.


Because of the potential for systemic absorption, use of topical corticosteroids may require that patients be periodically evaluated for HPA axis suppression.


Conditions which increase systemic absorption include the use of more potent corticosteroids, use over large surface areas, use over prolonged periods, and use of occlusive dressings.


Children may be more susceptible to systemic toxicity from equivalent doses due to heir larger skin surface to body mass ratios.


Local adverse reactions may occur with use of topical corticosteroids and may be more likely to occur with occlusive use, prolonged use or use of higher potency corticosteroids. Some local adverse reactions may be irreversible. Reactions may include atrophy, striae, telangiectasias, burning, itching, irritation, dryness, folliculitis, acneiform eruptions, hypopigmentation, perioral dermatitis, allergic contact dermatitis, secondary infection, and miliaria.


Concomitant skin infections should be treated with an appropriate antimicrobial agent.


Physicians should use caution in prescribing Derma-Smoothe Body Oil for peanut-sensitive individuals. Should signs of hypersensitivity present (wheal and flare reactions, pruritus, or other manifestations), or should disease exacerbations occur, Derma-Smoothe Body Oil should be discontinued immediately and appropriate therapy instituted.


The most common adverse reactions are cough, rhinorrhea, pyrexia, telangiectasia, nasopharyngitis, and hypopigmentation.

Omission and Minimization of Risk Information/Unsubstantiated Safety Superiority Claims


The webpages are misleading because they omit and minimize important risks associated with the use of Derma-Smoothe Body Oil, thus implying the drug is safer than has been demonstrated.


The webpages make claims such as the following regarding the lack of adrenal suppression with the use of Derma-Smoothe Body Oil (underline and bolded emphasis in original):


• “. . . [N]O Adrenal Suppression!”


• “The only corticosteroid that does not cause adrenal suppression, even when used over 90% of the body!”


“How safe is DERMA-SMOOTHE/FS® (BODY OIL)? Will there be side effects from long-term use?


DERMA-SMOOTHE/FS® (BODY OIL) is the safest topical corticosteroid and the only topical steroid shown not to cause adrenal suppression in children, even when used over as much as 90% of the body.”


These claims are particularly troubling because they minimize the warnings and precautions regarding HPA axis suppression that are included in the PI for Derma-Smoothe Body Oil. Specifically, the PI warns that systemic absorption of topical corticosteroids can produce reversible HPA axis suppression, and that use of topical corticosteroids over large surface areas can increase systemic absorption. Further, the PI contains a warning that children may be more susceptible to systemic toxicity from equivalent doses due to their larger skin surface to body mass ratios. While HPA axis suppression was not seen in the small, open-label pediatric clinical studies for Derma-Smoothe Body Oil, it does not dismiss the possibility of HPA axis suppression in patients who use Derma-Smoothe Body Oil. Further, these claims misleadingly suggest Derma-Smoothe Body Oil is superior in safety to other topical corticosteroids because it is the only product that does not cause adrenal suppression. FDA is not aware of adequate and well-controlled head-to-head studies to support this claim.


Additionally, FDA is not aware of any substantial evidence or substantial clinical experience to support the claim that Derma-Smoothe Body Oil is the “safest” topical corticosteroid. In fact, Derma-Smoothe Body Oil has the potential to cause the same types of side effects as other topical corticosteroids. If you have any data to support the claim that Derma-Smoothe Body Oil is the “safest” topical corticosteroid, please submit them to FDA for review.


What is even more concerning is that one of the webpages contains an image of a baby holding a circular sign in which “Safety Concerns” is crossed-out. This image creates the misleading impression that there are no safety concerns with Derma-Smoothe Body Oil, when this is not the case. Derma-Smoothe Body Oil is associated with numerous risks, as reflected in the warnings and precautions and adverse reactions sections of its PI.


Further, the webpages include the following presentation regarding the use of Derma-Smoothe Body Oil in children allergic to peanuts (emphasis in original):
 

“My child is allergic to peanuts. Can he use DERMA-SMOOTHE/FS® (BODY OIL)?


Peanut allergies are not a problem with DERMA-SMOOTHE/FS® (BODY OIL)! It is well known that it is the protein in peanuts that causes the allergic reaction in peanut-sensitive individuals. DERMA-SMOOTHE/FS® (BODY OIL) contains refined peanut oil which under routine tests for protein levels, do not show any protein. Studies conducted at Chicago Children’s Hospital and at The Mayo Clinic in Rochester, Minnesota confirm that DERMA-SMOOTHE/FS® (BODY OIL) is safe for peanut sensitive individuals.”


The totality of this presentation is misleading because it dismisses the fact that the PI for Derma-Smoothe Body Oil contains warnings and precautions regarding use in peanut sensitive individuals. The PI states that physicians should use caution in prescribing Derma-Smoothe Body Oil for peanut-sensitive individuals and should signs of hypersensitivity present or should disease exacerbations occur, Derma-Smoothe Body Oil should be immediately discontinued and appropriate therapy instituted. While FDA has acknowledged that the refinement process reduces peanut oil to a level below that likely to cause an allergic reaction in peanut sensitive individuals, FDA continues to require that the labeling for Derma-Smoothe Body Oil include cautionary statements about use by peanut sensitive individuals. FDA is not aware of any substantial evidence or substantial clinical experience to support a change in the product labeling regarding these warnings and precautions. If you have any data to support a labeling change, please submit them to FDA as a labeling supplement for review.


The webpages present various efficacy claims for Derma-Smoothe Body Oil, but fail to communicate any important risk information from the warnings and precautions and adverse reactions sections of the PI. We note that each of the webpages include a link to the PI; however, this does not correct the misleading omission and minimization of risk information from the webpages. For promotional materials to be truthful and non-misleading, they must contain risk information in each part as necessary to qualify any effectiveness or safety claims made in that part. By omitting the most serious and frequently occurring risks associated with Derma-Smoothe Body Oil, the webpages misleadingly suggest that the drug product is safer than has been demonstrated.


Overstatement of Efficacy/ Unsubstantiated Superiority Claims


Promotional materials are misleading if they represent or suggest that a drug is more effective than has been demonstrated by substantial evidence or substantial clinical experience.


The webpages include claims such as the following regarding the results that patients can expect from the use of Derma-Smoothe Body Oil (underline emphasis added):


• Image of a baby holding a circular sign in which “Disappointing Results” and “Outrageous Prices” are each crossed-out


• “Patient cost is only $45.00 for a full course of treatment!”


• “Patients enrolled in the clinical studies had symptoms of the disease (itchy, dry, inflamed, red skin), on the average, over 75% of their bodies. Some had as much as 95% involvement. These patients used one to two bottles of DERMA-SMOOTHE/FS® (BODY OIL) over a 4-week period of time to eliminate the symptoms.”


• “If you are paying out of pocket (without insurance), you can expect to pay approximately $39.00-$45.00 for one, 4 oz. bottle of DERMA-SMOOTHE/FS® (BODY OIL). In clinical trials, one bottle of DERMA-SMOOTHE/FS® (BODY OIL) was usually sufficient to eliminate a patient’s symptoms in severe cases where anywhere from 50% to 90% of the body was involved.”


The totality of this presentation misleadingly implies that, as compared to other available treatment options, a full course of treatment consisting of one to two bottles of Derma-Smoothe Body Oil will eliminate the symptoms of atopic dermatitis. However, FDA is not aware of substantial evidence or substantial clinical experience to support the claims that one to two bottles of Derma-Smoothe Body Oil constitute a full course of treatment and that one to two bottles of Derma-Smoothe Body Oil will eliminate the symptoms of atopic dermatitis. In the clinical data submitted to FDA for use of Derma-Smoothe Body Oil for the treatment of atopic dermatitis in patients 3 months of age and older, the number of bottles of product used by patients was not provided. In addition, FDA is not aware of substantial evidence or substantial clinical experience to support the drug’s superior efficacy for the treatment of symptoms of atopic dermatitis as compared to other treatment options. If you have any data to support these claims, please submit them to FDA for review.


The webpages make claims such as the following regarding Derma-Smoothe Body Oil and skin barrier function (emphasis in original)


• “When applied to moistened skin, the product softens and maintains hydration in the skin each time DERMA-SMOOTHE/FS® (BODY OIL) is applied. The skin barrier function is restored quickly and the itching, dryness and redness are eliminated within a very short period of time.”


Such claims are misleading because they imply that Derma-Smoothe Body Oil has been demonstrated to repair skin barrier function; however, FDA is not aware of any substantial evidence or substantial clinical experience to support such claims. If you have any data to support such claims, please submit them to FDA for review.


Further, the webpages include the following claim:


• “It not only eliminates the symptoms of the disease, but also keeps the child’s skin soft and normal looking for long periods of time by helping to prevent flare-ups.”
 

This claim is misleading because it implies that Derma-Smoothe Body Oil will keep a child’s skin soft and normal looking for long periods of time; however, FDA is not aware of substantial evidence or substantial clinical experience to support the claim that Derma-Smoothe Body Oil will keep a child’s skin “soft and normal looking.” We note that the PI includes adverse reactions that would prevent the skin from appearing “normal looking,” such as hyperpigmentation and hypopigmentation. In addition, this claim is misleading because it implies that Derma-Smoothe Body Oil not only eliminates the symptoms of atopic dermatitis, but that it works for a long period of time by helping to prevent flare-ups. FDA is not aware of any adequate and well-controlled trials assessing time to relapse; therefore claims implying that Derma-Smoothe Body Oil works for a long period of time by helping to prevent flare-ups are misleading. In fact, we note that Derma-Smoothe Body Oil is only indicated for the treatment of moderate to severe atopic dermatitis in pediatric patients 3 months and older and not for the prevention of disease flares.


Broadening of Indication/Inadequate Communication of the Indication

Promotional materials are misleading if they suggest that a drug is useful in a broader range of patients or conditions than has been demonstrated by substantial evidence or substantial clinical experience. The webpages make claims and presentations such as the following (underlined and bolded emphasis in original):


“Derma-Smoothe/FS® (Body Oil) (fluocinolone acetonide oil), 0.01% Severe and All Over . . . 3 mos and NO Adrenal Suppression! [graphic includes a teddy bear holding onto the number “3” within a background of diaper pins]


Hill Dermaceuticals has a treatment for childhood eczema. Pediatric Dermatitis is a type of eczema that affects children.


. . . Hill Dermaceuticals provides skin treatment solutions that are safe and effective for children of all ages suffering from this disease.”


• “The only product for patients 3 months and older that can be used when their eczema is severe and all over!”


• “DERMA-SMOOTHE/FS® (BODY OIL) was specifically formulated for the treatment of widespread Atopic Dermatitis of the body. It is approved for children.”


The totality of these claims and presentations is misleading because it fails to adequately communicate the indication of Derma-Smoothe Body Oil. While some of the webpages convey the fact that Derma-Smoothe Body Oil is indicated in pediatric patients 3 months of age and older, they fail to convey the full indication of the product in that it is indicated for moderate to severe atopic dermatitis in pediatric patients 3 months of age and older for up to 4 weeks and that the safety and efficacy in pediatric patients less than 3 months of age have not been established. Additionally, claims and presentations such as those mentioned above regarding use all over the body, misleadingly broaden the indication. Derma-Smoothe Body Oil should not be used all over the body. The PI includes the important limitations that Derma-Smoothe Body Oil should not be applied to the diaper area; that the drug product should not be used on the face, axillae, or groin unless directed by the physician; and that application to intertriginous areas should be avoided due to the increased risk of local adverse reactions. Moreover, the PI states to apply the least amount of the drug product needed to cover the affected areas and it contains the warning and precaution that use over a large surface area is one condition that can increase systemic absorption, which can lead to reversible HPA axis suppression. By omitting Derma-Smoothe Body Oil’s full indication, along with its important limiting information, you misleadingly broaden the indication and minimize the risks of the drug product.


Unsubstantiated Claims


The webpages include the following claims (bolded emphasis in original):


“My child’s skin is so broken and irritated, he doesn’t like to be touched. Will this product burn?


DERMA-SMOOTHE/FS® (BODY OIL) is soothing to the skin. Wetting the skin with water before applying the oil will greatly reduce the possibility of experiencing a burning sensation.”


These claims are misleading because they imply that patients can expect their skin to be soothed upon using Derma-Smoothe Body Oil, and that patients can reduce their chances of experiencing a burning sensation when using the drug product if they would only wet their skin before application. FDA is not aware of any evidence to support either of these claims. If you have any data to support these claims, please submit them to FDA for review.


Conclusion and Requested Action


For the reasons discussed above, the “Pediatric Atopic Dermatitis” webpages of the Hill Dermaceuticals website misbrand Derma-Smoothe Body Oil in violation of the Act, 21 U.S.C. 352(a) & (n); 321(n), and FDA implementing regulations. See 21 CFR 202.1(e)(3)(i); (e)(5); (e)(6)(i) & (ii).


DDMAC requests that Hill Dermaceuticals immediately cease the dissemination of violative promotional materials for Derma-Smoothe Body Oil such as those described above. Please submit a written response to this letter on or before December 17, 2010, stating whether you intend to comply with this request, listing all promotional materials (with the 2253 submission date) for Derma-Smoothe Body Oil that contain violations such as those described above, and explaining your plan for discontinuing use of such violative materials. Because the violations described above are serious, we request, further, that your submission include a comprehensive plan of action to disseminate truthful, non-misleading, and complete corrective messages about the issues discussed in this letter to the audience(s) that received the violative promotional materials. Please direct your response to me at the Food and Drug Administration, Center for Drug Evaluation and Research, Division of Drug Marketing, Advertising, and Communications, 5901-B Ammendale Road, Beltsville, MD 20705-1266, or facsimile at 301-847-8444. In all future correspondence regarding this matter, please refer to MACMIS#19329 in addition to the NDA number. We remind you that only written communications are considered official.


The violations discussed in this letter do not necessarily constitute an exhaustive list. It is your responsibility to ensure that your promotional materials for Derma-Smoothe Body Oil comply with each applicable requirement of the Act and FDA implementing regulations.


Failure to correct the violations discussed above may result in FDA regulatory action, including seizure or injunction, without further notice.
 

Sincerely,
{See appended electronic signature page}
Thomas W. Abrams, RPh, MBA
Director
Division of Drug Marketing,
Advertising, and Communications

 

1 Pediatric Atopic Dermatitis webpages, at http://www.hillderm.com/skin-disease-treatments/pediatric-atopicdermatitis.shtml, http://www.hillderm.com/skin-disease-treatments/pediatric-atopic-dermatitis-popup.shtml, and http://www.hillderm.com/skin-disease-treatments/ped-atopic-dermatitis-detail.shtml (last accessed on November 9, 2010).


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This is a representation of an electronic record that was signed electronically and this page is the manifestation of the electronic signature.
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/s/
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THOMAS W ABRAMS
12/03/2010