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
Protopic Side Effects, and Drug Interactions - Tacrolimus
Protopic Side Effects, and Drug Interactions - Tacrolimus
SIDE EFFECTS
No phototoxicity and no photoallergenicity was detected in clinical studies
of 12 and 216 normal volunteers, respectively. One out of 198 normal volunteers
showed evidence of sensitization in a contact sensitization study.
In three randomized vehicle-controlled studies and two long-term safety studies,
655 and 571 patients respectively, were treated with PROTOPIC Ointment.
The following table depicts the adjusted incidence of adverse events pooled
across the 3 identically designed 12 week studies for patients in vehicle, PROTOPIC
Ointment 0.03%, and PROTOPIC Ointment 0.1% treatment groups, and the unadjusted
incidence of adverse events in two one year long-term safety studies, regardless
of relationship to study drug.
Incidence Of Treatment Emergent Adverse Events
|
|
12-Week Randomized, Double-Blind,
Phase 3 Studies
12-Week Adjusted Incidence Rate (%) |
Open-Label Studies
(up to 1 year) 0.1% Tacrolimius Ointment Incidence(%) |
|
|
Adult |
Pediatric |
Adult |
Pediatric |
|
|
Vehicle n=212 |
0.03%
Tacrolimus Ointment
n=210 |
0.1%
Tacrolimus
Ointment
n=209 |
Vehicle n=116 |
0.03%
Tacrolimus Ointment
n=118 |
n=316 |
n=255 |
|
Skin Burning *
|
26 |
46 |
58 |
29 |
43 |
47 |
26 |
|
Pruritus *
|
37 |
46 |
46 |
27 |
41 |
25 |
25 |
|
Flu-like symptoms *
|
19 |
23 |
31 |
25 |
28 |
22 |
35 |
|
Allergic Reaction
|
8 |
12 |
6 |
8 |
4 |
22 |
15 |
|
Skin Erythema
|
20 |
25 |
28 |
13 |
12 |
12 |
9 |
|
Headache *
|
11 |
20 |
19 |
8 |
5 |
10 |
18 |
|
Skin Infection
|
11 |
12 |
5 |
14 |
10 |
11 |
11 |
|
Fever
|
4 |
4 |
1 |
13 |
21 |
2 |
18 |
|
Infection
|
1 |
1 |
2 |
9 |
7 |
14 |
8 |
|
Cough Increased
|
2 |
1 |
1 |
14 |
18 |
3 |
15 |
|
Asthma
|
4 |
6 |
4 |
6 |
6 |
5 |
16 |
|
Herpes Simplex
|
4 |
4 |
4 |
2 |
0 |
12 |
5 |
|
Eczema Herpeticum
|
0 |
1 |
1 |
0 |
2 |
2 |
0 |
|
Pharyngitis
|
3 |
3 |
4 |
11 |
6 |
5 |
10 |
|
Accidental Injury
|
4 |
3 |
6 |
3 |
6 |
4 |
12 |
|
Pustular Rash
|
2 |
3 |
4 |
3 |
2 |
6 |
8 |
|
Folliculitis *
|
1 |
6 |
4 |
0 |
2 |
11 |
2 |
|
Rhinitis
|
4 |
3 |
2 |
2 |
6 |
5 |
5 |
|
Otitis Media
|
4 |
0 |
1 |
6 |
12 |
1 |
7 |
|
Sinusitis *
|
1 |
4 |
2 |
8 |
3 |
3 |
7 |
|
Diarrhea
|
3 |
3 |
4 |
2 |
5 |
4 |
6 |
|
Urticaria
|
3 |
3 |
6 |
1 |
1 |
5 |
5 |
|
Lack of Drug Effect
|
1 |
1 |
0 |
1 |
1 |
10 |
2 |
|
Bronchitis
|
0 |
2 |
2 |
3 |
3 |
3 |
6 |
|
Vomiting
|
0 |
1 |
1 |
7 |
6 |
1 |
5 |
|
Maculopapular Rash
|
2 |
2 |
2 |
3 |
0 |
4 |
3 |
|
Rash *
|
1 |
5 |
2 |
4 |
2 |
2 |
5 |
|
Abdominal Pain
|
3 |
1 |
1 |
2 |
3 |
1 |
5 |
|
Fungal Dermatitis
|
0 |
2 |
1 |
3 |
0 |
2 |
6 |
|
Gastroenteritis
|
1 |
2 |
2 |
3 |
0 |
4 |
2 |
|
Alcohol Intolerance *
|
0 |
3 |
7 |
0 |
0 |
6 |
0 |
|
Acne *
|
2 |
4 |
7 |
1 |
0 |
2 |
4 |
|
Sunburn
|
1 |
2 |
1 |
0 |
0 |
4 |
4 |
|
Skin Disorder
|
2 |
2 |
1 |
1 |
4 |
1 |
4 |
|
Conjunctivitis
|
0 |
2 |
2 |
2 |
1 |
4 |
2 |
|
Pain
|
1 |
2 |
1 |
0 |
1 |
4 |
3 |
|
Vesiculobullous Rash *
|
3 |
3 |
2 |
0 |
4 |
2 |
2 |
|
Lymphadenopathy
|
2 |
2 |
1 |
0 |
3 |
2 |
3 |
|
Nausea
|
4 |
3 |
2 |
0 |
1 |
1 |
2 |
|
Skin Tingling *
|
2 |
3 |
8 |
1 |
2 |
2 |
1 |
|
Face Edema
|
2 |
2 |
1 |
2 |
1 |
3 |
1 |
|
Dyspepsia *
|
1 |
1 |
4 |
0 |
0 |
1 |
4 |
|
Dry Skin
|
7 |
3 |
3 |
0 |
1 |
0 |
1 |
|
Hyperesthesia *
|
1 |
3 |
7 |
0 |
0 |
3 |
0 |
|
Skin Neoplasm
Benign ***
|
1 |
1 |
1 |
0 |
0 |
2 |
3 |
|
Back Pain *
|
0 |
2 |
2 |
1 |
1 |
3 |
1 |
|
Peripheral Edema
|
2 |
4 |
3 |
0 |
0 |
2 |
1 |
|
Varicella Zoster/
Herpes Zoster * **
|
0 |
1 |
0 |
0 |
5 |
1 |
3 |
|
Contact Dermatitis
|
1 |
3 |
3 |
3 |
4 |
1 |
1 |
|
Asthenia
|
1 |
2 |
3 |
0 |
0 |
2 |
1 |
|
Pneumonia
|
0 |
1 |
1 |
2 |
0 |
1 |
2 |
|
Eczema
|
2 |
2 |
2 |
0 |
0 |
3 |
0 |
|
Insomnia
|
3 |
4 |
3 |
1 |
1 |
1 |
0 |
|
Exfoliative Dermatitis
|
3 |
3 |
1 |
0 |
0 |
0 |
2 |
|
Dysmenorrhea
|
2 |
4 |
4 |
0 |
0 |
0 |
2 |
|
Periodontal Abscess
|
1 |
0 |
1 |
0 |
0 |
3 |
0 |
|
Myalgia *
|
0 |
3 |
2 |
0 |
0 |
1 |
0 |
|
Cyst *
|
0 |
1 |
3 |
0 |
0 |
0 |
0 |
|
* May be reasonably associated with the use
of this drug product
** Four cases of chicken pox in the pediatric
12-week study, 1 case of "zoster of the lip" in the adult 12-week study;
7 cases of chicken pox and 1 case of shingles in the open-label pediatric
study; 2 cases of herpes zoster in the open-label adult study.
*** Generally "warts".
|
Other adverse events which occurred at an incidence greater than or equal to
1% in any clinical study include: alopecia, ALT or AST increased, anaphylactoid
reaction, angina pectoris, angioedema, anorexia, anxiety, arrhythmia, arthralgia,
arthritis, bilirubinemia, breast pain, cellulitis, cerebrovascular accident,
cheilitis, chills, constipation, creatinine increased, dehydration, depression,
dizziness, dyspnea, ear pain, ecchymosis, edema, epistaxis, exacerbation of
untreated area, eye disorder, eye pain, furunculosis, gastritis, hemia, hyperglycemia,
hypertension, hypoglycemia, hypoxia, laryngitis, leukocytosis, leukopenia, liver
function tests abnormal, lung disorder, malaise, migraine, neck pain, neuritis,
palpitations, paresthesia, peripheral vascular disorder, photosensitivity reaction,
procedural complication, routine procedure, skin discoloration, sweating, taste
perversion, tooth disorder, unintended pregnancy, vaginal moniliasis, vasodilatation,
and vertigo.
DRUG INTERACTIONS
Formal topical drug interaction studies with PROTOPIC Ointment have not been
conducted. Based on its minimal extent of absorption, interactions of PROTOPIC
Ointment with systemically administered drugs are unlikely to occur but cannot
be ruled out. The concomitant administration of known CYP3A4 inhibitors in patients
with widespread and/or erythrodermic disease should be done with caution. Some
examples of such drugs are erythromycin, itraconazole, ketoconazole, fluconazole,
calcium channel blockers and cimetidine.
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