What is Protopic (tacrolimus ointment)?

Protopic (tacrolimus ointment) is an immunosuppressant topical drug (applied to the skin) used to treat atopic dermatitis (eczema). 

Atopic dermatitis is a chronic skin disease in which the skin becomes inflamed, causing itchiness, redness, swelling, cracking, weeping, crusting, and scaling. The inflammation is caused by activation of the immune system though the reason for the activation is unknown. 

Protopic suppresses the immune system and the inflammation by inhibiting an enzyme (calcineurin) crucial for the multiplication of T-cells, cells that are required for activation of the immune system. 

Common side effects of Protopic include:

Serious side effects of Protopic include:

No studies have been done to determine if Protopic has important interactions with other drugs. Interactions are unlikely because only small amounts of Protopic are absorbed from the skin; however, it is possible that important interactions might occur. Only small amounts of Protopic are absorbed from the ointment, and it is not known if these amounts are toxic to a fetus. 

Among women who have received oral tacrolimus while pregnant, high potassium levels and kidney injury have been reported in their newborns. Protopic should be used during pregnancy only if the benefits outweigh the potential risks to the fetus. 

Only small amounts of Protopic are absorbed from the ointment, and it is not known how much, if any, appears in breast milk. Tacrolimus, when taken orally, passes into breast milk. Consideration should be given to discontinuing either breastfeeding or Protopic in nursing mothers.

What are the important side effects of Protopic (tacrolimus ointment)?

The most common side effects of tacrolimus ointment are skin reactions at the site of use, including:

Continuous long-term use of tacrolimus should be avoided because rare cases of skin cancer and lymphoma have occurred during tacrolimus treatment.

Protopic (tacrolimus ointment) side effects list for healthcare professionals

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.

Duration of Follow-up in Four Open-label Safety Studies

Time on StudyAdultPediatricsTotal
< 1 year468244819163
≥ 1 year118513492534
≥ 2 years200275475
≥ 3 years118182300

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.

Incidence of Treatment Emergent Adverse Events

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 (%)
AdultPediatricAdultPediatricTotal
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†2646582943282024
Pruritus†3746462741251922
Flu-like symptoms†1923312528223428
Allergic Reaction81268491311
Skin Erythema20252813121279
Headache†1120198513911
Skin Infection11125141091612
Fever44113212148
Infection112976108
Cough Increased21114183106
Asthma464664138
Herpes Simplex44420433
Eczema Herpeticum01102000
Pharyngitis3341164128
Accidental Injury43636687
Pustular Rash23432275
Folliculitis†16402423
Rhinitis43226243
Otitis Media4016122116
Sinusitis†14283676
Diarrhea33425243
Urticaria33611344
Lack of Drug Effect11011666
Bronchitis02233444
Vomiting01176143
Maculopapular Rash22230211
Rash†15242233
Abdominal Pain31123132
Fungal Dermatitis02130243
Gastroenteritis12230243
Alcohol Intolerance†03700402
Acne†24710323
Sunburn12100211
Skin Disorder22114222
Conjunctivitis02221333
Pain12101212
Vesiculobullous Rash†33204211
Lymphadenopathy22103121
Nausea43201212
Skin Tingling†23812211
Face Edema22121111
Dyspepsia†11400222
Dry Skin73301111
Hyperesthesia†13700201
Skin Neoplasm Benign‡‡11100122
Back Pain†02211302
Peripheral Edema24300201
Varicella Zoster/Herpes Zoster† ‡01005122
Contact Dermatitis13334222
Asthenia12300101
Pneumonia01120132
Eczema22200101
Insomnia34311201
Exfoliative Dermatitis33100010
Dysmenorrhea24400211
Periodontal Abscess10100111
Myalgia†03200211
Cyst†01300101
Cellulitis11100111
Exacerbation of Untreated Area10110111
Procedural Complication10010111
Hypertension00100201
Tooth Disorder01110211
Arthralgia11320212
Depression12100101
Paresthesia13300212
Alopecia01100111
Urinary Tract Infection00100212
Ear Pain10101011
† May be reasonably associated with the use of this drug product
‡ All the herpes zoster cases in the pediatric 12-week study and the majority of cases in the open-label pediatric studies were reported as chicken pox.
‡‡ Generally “warts”.

Other adverse events which occurred at an incidence between 0.2% and less than 1% in clinical studies in the above table include:

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

Infections

Bullous impetigo, osteomyelitis, septicemia

Neoplasms

Lymphomas, basal cell carcinoma, squamous cell carcinoma, malignant melanoma

Renal

Acute renal failure in patients with or without Netherton's syndrome, renal impairment

Skin

Rosacea, application site edema

What drugs interact with Protopic (tacrolimus ointment)?

Formal topical drug interaction studies with Protopic Ointment have not been conducted. Based on its 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:

Summary

Protopic (tacrolimus ointment) is an immunosuppressant topical drug (applied to the skin) used to treat atopic dermatitis (eczema). Common side effects of Protopic include redness, burning, itching, flu-like symptoms, allergic reactions, and headache. Serious side effects of Protopic include rare cases of skin cancer and lymphoma due to continuous long-term use. Among women who have received oral tacrolimus while pregnant, high potassium levels and kidney injury have been reported in their newborns. Protopic should be used during pregnancy only if the benefits outweigh the potential risks to the fetus. Only small amounts of Protopic are absorbed from the ointment, and it is not known how much, if any, appears in breast milk.

Treatment & Diagnosis

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Medically Reviewed on 5/11/2020
References
FDA Prescribing Information

Professional side effects and drug interactions sections courtesy of the U.S. Food and Drug Administration.
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