The following adverse reactions are discussed in greater detail in other sections of the labeling:
- HPA Axis Suppression and Other Adverse Endocrine Effects [see WARNINGS AND PRECAUTIONS]
- Local Adverse Reactions [see WARNINGS AND PRECAUTIONS]
- Concomitant Skin Infections [see WARNINGS AND PRECAUTIONS]
Clinical Trials Experience: Controlled Clinical Trials
Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared to rates in the clinical trials of another drug and may not reflect the rates observed in practice.
In 2 multicenter vehicle-controlled clinical trials of once-daily application of CUTIVATE® Lotion by 196 adult and 242 pediatric patients, the total incidence of adverse reactions considered drug related by investigators was approximately 4%. These were local cutaneous reactions, usually mild and self-limiting, and consisted primarily of burning/stinging (2%). All other drug-related events occurred with an incidence of less than 1%, and included were contact dermatitis, exacerbation of atopic dermatitis, folliculitis of legs, pruritus, pustules on arm, rash, and skin infection. See Table 1.
The incidence of adverse reactions between the 242 pediatric subjects (age 3 months to < 17 years) and 196 adult subjects (17 years or older) was similar (4% and 5%, respectively).
Table 1: Adverse Reactions from Controlled Clinical Trials (N=438)
|Adverse Reactions||CUTIVATE® Lotion
|Buming/Stinging skin||4 (2%)||3 (1%)|
|Contact Dermatitis||0||1 ( < 1%)|
|Exacerbation of Atopic dermatitis||0||1 ( < 1%)|
|Folliculitis of legs||2 ( < 1%)||0|
|Irritant Contact Dermatitis||0||1 ( < 1%)|
|Pruritus||1 ( < 1%)||1 ( < 1%)|
|Pustules on Arms||1 ( < 1%)||0|
|Rash||1 ( < 1%)||2 ( < 1%)|
|Skin Infection||0||3 (1%)|
During the clinical trials, eczema herpeticum occurred in a 33-year old male patient treated with CUTIVATE® Lotion.
Table 2 summarizes all adverse events by body system that occurred in at least 1% of patients in either the drug or vehicle group in the phase 3 controlled clinical trials.
Table 2: Adverse Events Occurring in ≥ 1% of Patients from Either Arm from Controlled Clinical Trials (n=438)
|Body System||CUTIVATE® Lotion
N = 221
|Any Adverse Event||77 (35%)||82 (38%)|
|Burning and Stinging||4 (2%)||3 (1%)|
|Pruritus||3 (1%)||5 (2%)|
|Rash||2 ( < 1%)||3 (1%)|
|Skin Infection||0||3 (1%)|
|Ear, Nose, Throat|
|Common Cold||9 (4%)||5 (2%)|
|Ear Infection||3 (1%)||3 (1%)|
|Nasal Sinus Infection||2 ( < 1%)||4 (2%)|
|Rhinitis||1 ( < 1%)||3 (1%)|
|Upper Respiratory Tract Infection||6 (3%)||7 (3%)|
|Normal Tooth Eruption||2 ( < 1%)||3 (1%)|
|Vomiting||3 (1%)||2 ( < 1%)|
|Cough||7 (3%)||6 (3%)|
|Headache||4 (2%)||5 (2%)|
|Fever||8 (4%)||8 (4%)|
|Seasonal Allergy||2 ( < 1%)||3 (1%)|
Clinical Trials Experience: Pediatric Open Label Trials
In an open label HPA axis suppression trial of 44 pediatric subjects (ages ≥3 months to ≤ 6 years) CUTIVATE® Lotion was applied twice daily (rather than the indicated dosing regimen of once daily) to at least 35% of body surface area for 3 or 4 weeks. Subjects whose lesions cleared after 2 or 3 weeks of treatment continued to apply CUTIVATE® Lotion for an additional week. The overall incidence of adverse reactions was 14%. These were local, cutaneous reactions and included dry skin (7%), stinging at application site (5%), and excoriation (2%). Additionally, a 4-month-old patient treated with CUTIVATE® Lotion had marked elevations of the hepatic enzymes AST and ALT. [see Use in Specific Populations]
In another open label HPA axis suppression trial in which CUTIVATE® Lotion was also applied twice daily (rather than the indicated dosing regimen of once daily), 56 pediatric subjects (ages ≥3 months to 12 months), were enrolled [see Use in Specific Populations].
The adverse reactions included 2 cases of Herpes simplex at the application site (3.6%) and 3 cases of bacterial skin infections (5.4%).
The following local adverse reactions have been identified during post-approval use of CUTIVATE® Lotion: erythema, edema/swelling, and bleeding.
The following systemic adverse reactions have been identified during post-approval use of CUTIVATE® Cream and CUTIVATE® Ointment: immunosuppression/Pneumocystis jirovecii pneumonia/leukopenia/thrombocytopenia; hyperglycemia/ glycosuria; Cushing syndrome; generalized body edema/blurred vision; and acute urticarial reaction (edema, urticaria, pruritus, and throat swelling).
The following local adverse reactions have also been reported with the use of topical corticosteroids, and they may occur more frequently with the use of occlusive dressings or higher potency corticosteroids. These reactions include: acneiform eruptions, hypopigmentation, perioral dermatitis, skin atrophy, striae, hypertrichosis and miliaria.
Because these reactions are reported voluntarily from a population of uncertain size, it is not always possible to reliably estimate their frequency or establish a causal relationship to drug exposure.