A1,
A2,
B,
C1,
C2,
D,
E,
F,
G-H,
I-K,
L,
M,
N,
O,
P1,
P2,
Q-R,
S,
T,
U-V,
W-Z
Solage Side Effects, and Drug Interactions - Mequinol & Tretinoin
Solage Side Effects, and Drug Interactions - Mequinol & Tretinoin
SIDE EFFECTS
In clinical trials, adverse reactions were primarily mild to
moderate in intensity, occurring in 66% and 30% of patients, respectively. The
majority of these events were limited to the skin and 64% had an onset of a
skin related adverse reaction early in treatment (by week 8). The most frequent
adverse reactions in patients treated with Solagé were erythema (49%
of patients), burning, stinging or tingling (26%), desquamation (14%), pruritus
(12%), and skin irritation (5%).
Some patients experienced temporary hypopigmentation of treated
lesions (5%) or of the skin surrounding treated lesions (7%). Ninety-four of
106 patients (89%) had resolution of hypopigmentation upon discontinuation of
treatment to the lesion, and/or re-instruction on proper application to the
lesion only. Another 8% (9/106) of patients with hypopigmentation events had
resolution within 120 days after the end of treatment. Three of the 106 patients
(2.8%) had persistence of hypopigmentation beyond 120 days.
Approximately 6% of patients discontinued study participation
with Solagé due to adverse reactions. These discontinuations were due
primarily to skin redness (erythema) or related cutaneous adverse reactions.
Solagé was generally well tolerated.
Adverse Events Occurring in >1% of the Population All Studies
|
Body System
|
Solagé (mequinol
2%, tretinoin 0.01%)
|
Tretinoin, 0.01%
|
Mequinol, 2%
|
Vehicle
|
|
N
|
%
|
N
|
%
|
N
|
%
|
N
|
%
|
|
Skin and Appendages Erythema
|
421
|
49.4
|
261
|
55.3
|
13
|
5.1
|
8
|
4.6
|
|
Burning/Stinging/Tingling
|
223
|
26.1
|
173
|
36.7
|
26
|
10.2
|
20
|
11.4
|
|
Desquamation
|
120
|
14.1
|
93
|
19.7
|
7
|
2.8
|
2
|
1.1
|
|
Pruritus
|
105
|
12.3
|
66
|
14.0
|
12
|
4.7
|
3
|
1.7
|
|
Halo Hypopigmentation
|
60
|
7.0
|
16
|
3.4
|
2
|
0.8
|
2
|
1.1
|
|
Hypopigmentation
|
46
|
5.4
|
8
|
1.7
|
2
|
0.8
|
0
|
0.0
|
|
Irritation Skin
|
45
|
5.3
|
25
|
5.3
|
1
|
0.4
|
1
|
0.6
|
|
Rash
|
27
|
3.2
|
21
|
4.4
|
0
|
0.0
|
1
|
0.6
|
|
Skin Dry
|
27
|
3.2
|
18
|
3.8
|
3
|
1.2
|
1
|
0.6
|
|
Crusting
|
21
|
2.5
|
18
|
3.8
|
0
|
0.0
|
1
|
0.6
|
|
Rash Vesicular Bullae
|
18
|
2.1
|
8
|
1.7
|
0
|
0.0
|
0
|
0.0
|
|
Application Site Reaction*
|
9
|
1.1
|
11
|
2.3
|
1
|
0.4
|
0
|
0.0
|
* Events that were considered to be a contact allergic reaction
DRUG INTERACTIONS
Concomitant topical products with a strong skin drying effect,
products with high concentrations of alcohol, astringents, spices or lime, medicated
soaps or shampoos, permanent wave solutions, electrolysis, hair depilatories
or waxes, or other preparations that might dry or irritate the skin should be
used with caution in patients being treated with Solagé
because they may increase irritation when used with Solagé
.
Solagé should not be administered
if the patient is also taking drugs known to be photosensitizers (e.g., thiazides,
tetracyclines, fluoroquinolones, phenothiazines, sulfonamides) because of the
possibility of augmented phototoxicity.
Carcinogenesis, Mutagenesis, Impairment of Fertility:
Although a dermal carcinogenicity study in CD-1 mice indicated that Solagé
applied topically at daily doses up to 80 and 0.4 mg/kg (240 and 1.2 mg/m2)
of mequinol and tretinoin, respectively, representing approximately 5 times
the maximum possible systemic human exposure was not carcinogenic, in a photocarcinogenicity
study utilizing Crl:Skh-1(hr/hr BR) hairless albino mice, median time to onset
of tumors decreased. Also, the number of tumors increased in all dose
groups administered 1.4, 4.3, or 14 µl of Solagé/cm2 of skin
(24 and 0.12, 72 and 0.36, or 240 and 1.2 mg/m2 of mequinol and tretinoin,
respectively; 0.6, 1.9, or 6.5 times the daily human dose on a mg/m2
basis) following chronic topical dosing with intercurrent exposure to ultraviolet
radiation for up to 40 weeks. Similar animal studies have shown an increased
tumorigenic risk with the use of retinoids when followed by ultraviolet radiation.
Although the significance of these studies to human use is not clear, patients
using this product should be advised to avoid or minimize exposure to either
sunlight or artificial ultraviolet irradiation sources.
Mequinol was non-mutagenic in the Ames/Salmonella assay using
strains TA98, TA100, TA1535, and TA1537, all of which are insensitive to mutagenic
effects of structurally-related quinones. Solagé was non-genotoxic in
an in vivo dermal micronucleus assay in rats, but exposure of bone marrow to
drug was not demonstrated.
A dermal reproduction study with Solagé in Sprague-Dawley
rats at a daily dose of 80 and 0.4 mg/kg (480 and 2.4 mg/m2) of mequinol
and tretinoin, respectively, approximately 11 times the corresponding maximum
possible human exposure, assuming 100% bioavailablity following topical application
to 5% of the total body surface area, showed no impairment of fertility.
Pregnancy: Teratogenic effects: Pregnancy Category X. Although
the magnitude of the potential for teratogenicity may not be well-defined, Solagé
is labeled as an "X" because the potential risk of the use of this
drug to treat this particular indication (solar lentigines) in a pregnant woman
clearly outweighs any possible benefit (See CONTRAINDICATIONS
Section).
Nursing mothers: It is not known to what extent mequinol
and/or tretinoin is excreted in human milk. Because many drugs are excreted
in human milk, caution should be exercised when Solagé is administered
to a nursing woman.
Pediatric Use: The safety and effectiveness of this
product have not been established in pediatric patients. Solagé should
not be used on children.
Geriatric Use: Of the total number of patients in clinical
studies of Solagé , approximately 43% were 65 and older, while approximately
8% were 75 and over. No overall differences in effectiveness or safety were
observed between these patients and younger patients.
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