Protopic Side Effects
Please note - some side effects for Protopic may not be reported. Always consult your doctor or healthcare specialist for medical advice. You may also report side effects to the FDA at http://www.fda.gov/medwatch/ or 1-800-FDA-1088 (1-800-332-1088).
Side Effects of Protopic - for the Consumer
Protopic Ointment
All medicines may cause side effects, but many people have no, or minor, side effects. Check with your doctor if any of these most COMMON side effects persist or become bothersome when using Protopic Ointment:
Seek medical attention right away if any of these SEVERE side effects occur when using Protopic Ointment:Acne; burning, stinging, soreness, itching, or redness of skin; flu-like symptoms; headache; upset stomach.
TopSevere allergic reactions (rash; hives; itching; difficulty breathing; tightness in the chest; swelling of the mouth, face, lips, or tongue); back pain; increased sensitivity to pain or touch; indigestion; nasal congestion; muscle pain; painful menstrual periods; sensitivity to pain; skin infection; swollen glands; swollen or infected hair follicles; weakness.
Protopic Side Effects - for the Professional
Protopic
No phototoxicity and no photoallergenicity were detected in clinical studies with 12 and 216 normal volunteers, respectively. One out of 198 normal volunteers showed evidence of sensitization in a contact sensitization study.
In three 12 week randomized vehicle-controlled studies and four safety studies, 655 and 9,163 patients respectively, were treated with Protopic Ointment. The duration of follow-up for adult and pediatric patients in the safety studies is tabulated below.
| Time on Study | Adult | Pediatrics | Total |
| < 1 year | 4682 | 4481 | 9163 |
| ≥ 1 year | 1185 | 1349 | 2534 |
| ≥ 2 years | 200 | 275 | 475 |
| ≥ 3 years | 118 | 182 | 300 |
The following table depicts the adjusted incidence of adverse events pooled across the 3 identically designed 12-week controlled studies for patients in vehicle, Protopic Ointment 0.03%, and Protopic Ointment 0.1% treatment groups. The table also depicts the unadjusted incidence of adverse events in four safety studies, regardless of relationship to study drug.
|
12-Week, Randomized, Double-Blind, Phase 3 Studies 12-Week Adjusted Incidence Rate (%) |
Open-Label Studies (up to 3 years) 0.1% and 0.03% Tacrolimus Ointment Incidence Rate (%) |
|||||||
|
Adult |
Pediatric |
Adult | Pediatric | Total | ||||
|
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=4682)% | (n=4481)% |
(n=9163) % |
|
| Skin Burning* | 26 | 46 | 58 | 29 | 43 | 28 | 20 | 24 |
| Pruritus* | 37 | 46 | 46 | 27 | 41 | 25 | 19 | 22 |
| Flu-like symptoms* | 19 | 23 | 31 | 25 | 28 | 22 | 34 | 28 |
| Allergic Reaction | 8 | 12 | 6 | 8 | 4 | 9 | 13 | 11 |
| Skin Erythema | 20 | 25 | 28 | 13 | 12 | 12 | 7 | 9 |
| Headache* | 11 | 20 | 19 | 8 | 5 | 13 | 9 | 11 |
| Skin Infection | 11 | 12 | 5 | 14 | 10 | 9 | 16 | 12 |
| Fever | 4 | 4 | 1 | 13 | 21 | 2 | 14 | 8 |
| Infection | 1 | 1 | 2 | 9 | 7 | 6 | 10 | 8 |
| Cough Increased | 2 | 1 | 1 | 14 | 18 | 3 | 10 | 6 |
| Asthma | 4 | 6 | 4 | 6 | 6 | 4 | 13 | 8 |
| Herpes Simplex | 4 | 4 | 4 | 2 | 0 | 4 | 3 | 3 |
| Eczema Herpeticum | 0 | 1 | 1 | 0 | 2 | 0 | 0 | 0 |
| Pharyngitis | 3 | 3 | 4 | 11 | 6 | 4 | 12 | 8 |
| Accidental Injury | 4 | 3 | 6 | 3 | 6 | 6 | 8 | 7 |
| Pustular Rash | 2 | 3 | 4 | 3 | 2 | 2 | 7 | 5 |
| Folliculitis* | 1 | 6 | 4 | 0 | 2 | 4 | 2 | 3 |
| Rhinitis | 4 | 3 | 2 | 2 | 6 | 2 | 4 | 3 |
| Otitis Media | 4 | 0 | 1 | 6 | 12 | 2 | 11 | 6 |
| Sinusitis* | 1 | 4 | 2 | 8 | 3 | 6 | 7 | 6 |
| Diarrhea | 3 | 3 | 4 | 2 | 5 | 2 | 4 | 3 |
| Urticaria | 3 | 3 | 6 | 1 | 1 | 3 | 4 | 4 |
| Lack of Drug Effect | 1 | 1 | 0 | 1 | 1 | 6 | 6 | 6 |
| Bronchitis | 0 | 2 | 2 | 3 | 3 | 4 | 4 | 4 |
| Vomiting | 0 | 1 | 1 | 7 | 6 | 1 | 4 | 3 |
| Maculopapular Rash | 2 | 2 | 2 | 3 | 0 | 2 | 1 | 1 |
| Rash* | 1 | 5 | 2 | 4 | 2 | 2 | 3 | 3 |
| Abdominal Pain | 3 | 1 | 1 | 2 | 3 | 1 | 3 | 2 |
| Fungal Dermatitis | 0 | 2 | 1 | 3 | 0 | 2 | 4 | 3 |
| Gastroenteritis | 1 | 2 | 2 | 3 | 0 | 2 | 4 | 3 |
| Alcohol Intolerance* | 0 | 3 | 7 | 0 | 0 | 4 | 0 | 2 |
| Acne* | 2 | 4 | 7 | 1 | 0 | 3 | 2 | 3 |
| Sunburn | 1 | 2 | 1 | 0 | 0 | 2 | 1 | 1 |
| Skin Disorder | 2 | 2 | 1 | 1 | 4 | 2 | 2 | 2 |
| Conjunctivitis | 0 | 2 | 2 | 2 | 1 | 3 | 3 | 3 |
| Pain | 1 | 2 | 1 | 0 | 1 | 2 | 1 | 2 |
| Vesiculobullous Rash* | 3 | 3 | 2 | 0 | 4 | 2 | 1 | 1 |
| Lymphadenopathy | 2 | 2 | 1 | 0 | 3 | 1 | 2 | 1 |
| Nausea | 4 | 3 | 2 | 0 | 1 | 2 | 1 | 2 |
| Skin Tingling* | 2 | 3 | 8 | 1 | 2 | 2 | 1 | 1 |
| Face Edema | 2 | 2 | 1 | 2 | 1 | 1 | 1 | 1 |
| Dyspepsia* | 1 | 1 | 4 | 0 | 0 | 2 | 2 | 2 |
| Dry Skin | 7 | 3 | 3 | 0 | 1 | 1 | 1 | 1 |
| Hyperesthesia* | 1 | 3 | 7 | 0 | 0 | 2 | 0 | 1 |
| Skin Neoplasm Benign† | 1 | 1 | 1 | 0 | 0 | 1 | 2 | 2 |
| Back Pain* | 0 | 2 | 2 | 1 | 1 | 3 | 0 | 2 |
| Peripheral Edema | 2 | 4 | 3 | 0 | 0 | 2 | 0 | 1 |
| Varicella Zoster/Herpes Zoster*‡ | 0 | 1 | 0 | 0 | 5 | 1 | 2 | 2 |
| Contact Dermatitis | 1 | 3 | 3 | 3 | 4 | 2 | 2 | 2 |
| Asthenia | 1 | 2 | 3 | 0 | 0 | 1 | 0 | 1 |
| Pneumonia | 0 | 1 | 1 | 2 | 0 | 1 | 3 | 2 |
| Eczema | 2 | 2 | 2 | 0 | 0 | 1 | 0 | 1 |
| Insomnia | 3 | 4 | 3 | 1 | 1 | 2 | 0 | 1 |
| Exfoliative Dermatitis | 3 | 3 | 1 | 0 | 0 | 0 | 1 | 0 |
| Dysmenorrhea | 2 | 4 | 4 | 0 | 0 | 2 | 1 | 1 |
| Periodontal Abscess | 1 | 0 | 1 | 0 | 0 | 1 | 1 | 1 |
| Myalgia* | 0 | 3 | 2 | 0 | 0 | 2 | 1 | 1 |
| Cyst* | 0 | 1 | 3 | 0 | 0 | 1 | 0 | 1 |
| Cellulitis | 1 | 1 | 1 | 0 | 0 | 1 | 1 | 1 |
| Exacerbation of Untreated Area | 1 | 0 | 1 | 1 | 0 | 1 | 1 | 1 |
| Procedural Complication | 1 | 0 | 0 | 1 | 0 | 1 | 1 | 1 |
| Hypertension | 0 | 0 | 1 | 0 | 0 | 2 | 0 | 1 |
| Tooth Disorder | 0 | 1 | 1 | 1 | 0 | 2 | 1 | 1 |
| Arthralgia | 1 | 1 | 3 | 2 | 0 | 2 | 1 | 2 |
| Depression | 1 | 2 | 1 | 0 | 0 | 1 | 0 | 1 |
| Paresthesia | 1 | 3 | 3 | 0 | 0 | 2 | 1 | 2 |
| Alopecia | 0 | 1 | 1 | 0 | 0 | 1 | 1 | 1 |
| Urinary Tract Infection | 0 | 0 | 1 | 0 | 0 | 2 | 1 | 2 |
| Ear Pain | 1 | 0 | 1 | 0 | 1 | 0 | 1 | 1 |
Other adverse events which occurred at an incidence between 0.2% and less than 1% in clinical studies in the above table include: abnormal vision, abscess, anaphylactoid reaction, anemia, anorexia, anxiety, arthritis, arthrosis, bilirubinemia, blepharitis, bone disorder, breast neoplasm benign, bursitis, cataract NOS, chest pain, chills, colitis, conjunctival edema, constipation, cramps, cutaneous moniliasis, cystitis, dehydration, dizziness, dry eyes, dry mouth/nose, dyspnea, ear disorder, ecchymosis, edema, epistaxis, eye pain, furunculosis, gastritis, gastrointestinal disorder, hernia, hypercholesterolemia, hypertonia, hypothyroidism, joint disorder, laryngitis, leukoderma, lung disorder, malaise, migraine, moniliasis, mouth ulceration, nail disorder, neck pain, neoplasm benign, oral moniliasis, otitis externa, photosensitivity reaction, rectal disorder, seborrhea, skin carcinoma, skin discoloration, skin hypertrophy, skin ulcer, stomatitis, tendon disorder, thinking abnormal, tooth caries, sweating, syncope, tachycardia, taste perversion, unintended pregnancy, vaginal moniliasis, vaginitis, valvular heart disease, vasodilatation, and vertigo.
Post-Marketing Events
The following adverse reactions have been identified during postapproval use of Protopic Ointment. 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.
CNS
Seizures
Neoplasms
Lymphomas, basal cell carcinoma, squamous cell carcinoma, malignant melanoma
Infections
Bullous impetigo, osteomyelitis, septicemia
Renal
Acute renal failure in patients with or without Netherton’s syndrome, renal impairment
Skin
Rosacea
Overdosage
Protopic Ointment is not for oral use. Oral ingestion of Protopic Ointment may lead to adverse effects associated with systemic administration of tacrolimus. If oral ingestion occurs, medical advice should be sought.
TopSide Effects by Body System
Dermatologic
Dermatologic effects have included skin burning (46% to 58%), pruritus (25% to 46%), skin erythema (12% to 28%), skin infection (5% to 12%), herpes simplex (4% to 12%), folliculitis (4% to 11%), pustular rash (3% to 6%), dry skin (3%), hyperesthesia (3% to 7%), urticaria (3% to 6%), skin tingling (2% to 8%), acne (2% to 7%), rash (2% to 5%), maculopapular rash (2% to 4%), vesiculobullous rash (2% to 4%), eczema (2% to 3%), sunburn (1% to 4%), skin disorder (1% to 4%), contact dermatitis (1% to 3%), exfoliative dermatitis (1% to 3%), fungal dermatitis (1% to 2%), eczema herpeticum (1% to 2%), benign skin neoplasm (1% to 2%), and varicella zoster/herpes zoster (1%). Other dermatologic side effects have included facial flushing, ecchymosis, cellulitis, skin discoloration, alopecia, angioedema, and sweating.
Oncologic
Oncologic side effects have included lymphoma and skin cancer. A definite causal relationship between these effects and tacrolimus topical has not been clearly established.
As of December 2004, nineteen postmarketing cases of cancer in patients receiving treatment with tacrolimus topical have been reported to the FDA MedWatch program. Ten cases were reported as cutaneous tumors (7 at site of application), 9 cases as lymphomas, and the remaining as a variety of tumors (including squamous cell carcinoma, cutaneous sarcoma, and malignant melanoma). Three of these cases were reported to have occurred in children, with the remaining 16 cases reported in adults. In addition, 6 of the cases reported lymphadenopathy. The median time to diagnosis was 150 days (range 21 to 790 days) following initiation of treatment with tacrolimus topical. Two deaths were reported in adults and 8 patients were hospitalized (6 adults, 2 children). Causality has not been established.
Gastrointestinal
Gastrointestinal side effects have included diarrhea (3% to 4%), gastroenteritis (2% to 4%), nausea (1% to 4%), dyspepsia (1% to 4%), abdominal pain (1% to 3%), and vomiting (1%). Other gastrointestinal side effects have included taste perversion, anorexia, and constipation.
Musculoskeletal
Musculoskeletal side effects have included back pain (2% to 3%), asthenia (2% to 3%), and myalgia (1% to 3%). Other musculoskeletal side effects have included arthritis, arthralgia, and neck pain.
Respiratory
Respiratory side effects have included asthma (4% to 6%), pharyngitis (3% to 5%), rhinitis (3% to 5%), sinusitis (2% to 5%), bronchitis (2% to 3%), increased cough (1% to 3%), and pneumonia (1%). Other respiratory side effects have included dyspnea, hypoxia, and lung disorder.
Nervous system
Nervous system side effects have included headache (10% to 20%), and insomnia (1% to 4%). Other nervous system side effects have included dizziness, anxiety, migraine, neuritis, and paresthesia.
Metabolic
Metabolic side effects have included increased ALT, AST, increased creatinine, hyperglycemia, hypoglycemia, and bilirubinuria.
Ocular
Ocular side effects have included conjunctivitis (2% to 4%). Other ocular side effects have included eye pain and eye disorder.
Immunologic
Immunologic symptoms have included flu like symptoms (22% to 31%), infection (1% to 14%), fever (1% to 4%), lymphadenopathy (1% to 3%), and periodontal abscess (1% to 3%). Other immunologic side effects have included leukocytosis and leukopenia.
Cardiovascular
Cardiovascular side effects have included peripheral edema (2% to 4%). Other cardiovascular side effects have included angina pectoris, cerebrovascular accident, peripheral vascular disorder, arrhythmias, palpitations, hypertension, and vasodilation.
General
General side effects have included lack of drug effect (1% to 10%), accidental injury (3% to 6%), alcohol intolerance (2% to 7%), facial edema (1% to 3%), pain (1% to 4%), and cyst (1% to 3%). Other general side effects have included chills, and increased dehydration.
Other
Other side effects have included otitis media (1%) and ear pain.
Genitourinary
Genitourinary side effects have included dysmenorrhea (2% to 4%). Other genitourinary side effects have included unintended pregnancy and vaginal moniliasis.
Local
Local side effects have included exacerbation of the untreated area.
Hepatic
Hepatic side effects have included liver function test abnormalities.
Psychiatric
Psychiatric side effects have included depression.
Hematologic
Hematologic side effects have included epistaxis.
TopMore resources:
Protopic Topical - Includes detailed dosage instructions.
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