NDC 54868-5233 Protopic

NDC Product Code 54868-5233

NDC CODE: 54868-5233

Proprietary Name: Protopic What is the Proprietary Name?
The proprietary name also known as the trade name is the name of the product chosen by the medication labeler for marketing purposes.

Drug Use Information

Drug Use Information
The drug use information is a summary and does NOT have all possible information about this product. This information does not assure that this product is safe, effective, or appropriate. This information is not individual medical advice and does not substitute for the advice of a health care professional. Always ask a health care professional for complete information about this product and your specific health needs.

  • This form of tacrolimus is used on the skin to treat a skin condition called eczema (atopic dermatitis) in patients who have not responded well to (or should not use) other eczema medications. Eczema is an allergic-type condition that causes red, irritated, and itchy skin. This drug works by weakening the skin's defense (immune) system, thereby decreasing the allergic reaction and relieving the eczema. Tacrolimus belongs to a class of drugs known as topical calcineurin inhibitors (TCIs). This medication is not recommended if you have a history of a certain rare genetic disorder (Netherton's syndrome). Also, this medication should not be used by anyone who has a weakened immune system (for example, following an organ transplant).

NDC Code Structure

NDC 54868-5233-0

Package Description: 100 g in 1 TUBE

NDC 54868-5233-1

Package Description: 30 g in 1 TUBE

This product is EXCLUDED from the official NDC directory because the listing data was inactivated by the FDA.

NDC Product Information

Protopic with NDC 54868-5233 is a product labeled by Physicians Total Care, Inc.. The product's dosage form is and is administered via form. The RxNorm Crosswalk for this NDC code indicates multiple RxCUI concepts are associated to this product: 284520 and 314266.

Inactive Ingredient(s)

About the Inactive Ingredient(s)
The inactive ingredients are all the component of a medicinal product OTHER than the active ingredient(s). The acronym "UNII" stands for “Unique Ingredient Identifier” and is used to identify each inactive ingredient present in a product.

  • MINERAL OIL (UNII: T5L8T28FGP)
  • PARAFFIN (UNII: I9O0E3H2ZE)
  • PROPYLENE CARBONATE (UNII: 8D08K3S51E)
  • PETROLATUM (UNII: 4T6H12BN9U)
  • WHITE WAX (UNII: 7G1J5DA97F)

Product Labeler Information

What is the Labeler Name?
Name of Company corresponding to the labeler code segment of the Product NDC.

Labeler Name: Physicians Total Care, Inc.
Labeler Code: 54868
Start Marketing Date: 05-08-2008 What is the Start Marketing Date?
This is the date that the labeler indicates was the start of its marketing of the drug product.

Listing Expiration Date: 12-31-2017 What is the Listing Expiration Date?
This is the date when the listing record will expire if not updated or certified by the product labeler.

Exclude Flag: I - INACTIVATED, the listing data was inactivated by the FDA. What is the NDC Exclude Flag?
This field indicates whether the product has been removed/excluded from the NDC Directory for failure to respond to FDA"s requests for correction to deficient or non-compliant submissions ("Y"), or because the listing certification is expired ("E"), or because the listing data was inactivated by FDA ("I"). Values = "Y", "N", "E", or "I".

* Please review the disclaimer below.

Information for Patients

Tacrolimus Topical

Tacrolimus Topical is pronounced as (ta kroe' li mus)

Why is tacrolimus topical medication prescribed?
Tacrolimus ointment is used to treat the symptoms of eczema (atopic dermatitis; a skin disease that causes the skin to be dry and itchy and to sometimes develop red, scal...
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* Please review the disclaimer below.

Protopic Product Labeling Information

The product labeling information includes all published material associated to a drug. Product labeling documents include information like generic names, active ingredients, ingredient strength dosage, routes of administration, appearance, usage, warnings, inactive ingredients, etc.

Product Labeling Index

Other

Rx OnlyPrescribing InformationSee boxed WARNINGS
concerning long-term safety of topical calcineurin inhibitors

Boxed Warning

  • WARNINGLong-term Safety of Topical Calcineurin Inhibitors Has Not
  • Been EstablishedAlthough a causal relationship has not been established, rare cases of
  • Malignancy (e.g., skin and lymphoma) have been reported in patients treated with
  • Topical calcineurin inhibitors, including PROTOPIC Ointment. Therefore:Continuous long-term use of topical calcineurin inhibitors, including
  • PROTOPIC Ointment, in any age group should be avoided, and application limited
  • To areas of involvement with atopic dermatitis.PROTOPIC Ointment is not indicated for use in children less than 2 years of
  • Age. Only 0.03% PROTOPIC Ointment is indicated for use in children 2-15 years of
  • Age.

Description

PROTOPIC (tacrolimus) Ointment contains tacrolimus, a macrolide
immunosuppressant produced by Streptomyces
tsukubaensis. It is for topical dermatologic use only. Chemically,
tacrolimus is designated as [3S-[3R*[E(1S*,3S*,4S*)],4S*,5R*,8S*,9E,12R*,14R*,15S*,16R*,18S*,19S*,26aR*]]-5,6,8,11,12,13,14,15,16,17,18,19,24,25,26,26a-hexadecahydro-5,19-dihydroxy-3-[2-(4-hydroxy-3-methoxycyclohexyl)-1-methylethenyl]-14,16-dimethoxy-4,10,
12,18-tetramethyl-8-(2-propenyl)-15,19-epoxy-3H-pyrido[2,1-c][1,4]
oxaazacyclotricosine-1,7,20,21(4H,23H)-tetrone,monohydrate. It has the following
structural formula: Tacrolimus has an empirical formula of C44H69NO12•H2O and a
formula weight of 822.03. Each gram of PROTOPIC Ointment contains (w/w) either
0.03% or 0.1% of tacrolimus in a base  of mineral oil, paraffin,
propylene carbonate, white petrolatum and white wax.

Clinical Pharmacology

Mechanism of Action The mechanism of action of tacrolimus in atopic dermatitis is not
known. While the following have been observed, the clinical significance of
these observations in atopic dermatitis is not known. It has been demonstrated
that tacrolimus inhibits T-lymphocyte activation by first binding to an
intracellular protein, FKBP-12. A complex of tacrolimus-FKBP-12, calcium,
calmodulin, and calcineurin is then formed and the phosphatase activity of
calcineurin is inhibited. This effect has been shown to prevent the
dephosphorylation and translocation of nuclear factor of activated T-cells
(NF-AT), a nuclear component thought to initiate gene transcription for the
formation of lymphokines (such as interleukin-2, gamma interferon). Tacrolimus
also inhibits the transcription for genes which encode IL-3, IL-4, IL-5, GM-CSF,
and TNF-α, all of which are involved in the early stages of T-cell activation.
Additionally, tacrolimus has been shown to inhibit the release of pre-formed
mediators from skin mast cells and basophils, and to down regulate the
expression of FcεRI on Langerhans cells.PharmacokineticsAbsorptionThe pooled results from three pharmacokinetic studies in 88 adult
atopic dermatitis patients indicate that tacrolimus is minimally absorbed after
the topical application of PROTOPIC Ointment. Peak tacrolimus blood
concentrations ranged from undetectable to 20 ng/mL after single or multiple
doses of 0.03% and 0.1% PROTOPIC Ointment, with 85% (75/88) of the patients
having peak blood concentrations less than 2 ng/mL. In general as treatment
continued, systemic exposure declined as the skin returned to normal. In
clinical studies with periodic blood sampling, a similar distribution of
tacrolimus blood levels was also observed in adult patients, with 90%
(1253/1391) of patients having a blood concentration less than 2 ng/mL. The absolute bioavailability of tacrolimus from PROTOPIC in atopic dermatitis
patients is approximately 0.5%. In adults with an average of 53% BSA treated,
exposure (AUC) of tacrolimus from PROTOPIC is approximately 30-fold less than
that seen with oral immunosuppressive doses in kidney and liver transplant
patients. Mean peak tacrolimus blood concentrations following oral administration (0.3
mg/kg/day) in adult kidney transplant (n=26) and liver transplant (n=17)
patients are 24.2±15.8 ng/mL and 68.5±30.0 ng/mL, respectively. The lowest
tacrolimus blood level at which systemic effects (e.g., immunosuppression) can
be observed is not known. Systemic levels of tacrolimus have also been measured in pediatric patients
(see Special Populations: Pediatrics).
DistributionThe plasma protein binding of tacrolimus is approximately 99% and
is independent of concentration over a range of 5-50 ng/mL. Tacrolimus is bound
mainly to albumin and alpha-1-acid glycoprotein, and has a high level of
association with erythrocytes. The distribution of tacrolimus between whole
blood and plasma depends on several factors, such as hematocrit, temperature at
the time of plasma separation, drug concentration, and plasma protein
concentration. In a US study, the ratio of whole blood concentration to plasma
concentration averaged 35 (range 12 to 67).There was no evidence based on blood concentrations that tacrolimus
accumulates systemically upon intermittent topical application for periods of up
to 1 year. As with other topical calcineurin inhibitors, it is not known whether
tacrolimus is distributed into the lymphatic system. MetabolismTacrolimus is extensively metabolized by the mixed-function
oxidase system, primarily the cytochrome P-450 system (CYP3A). A metabolic
pathway leading to the formation of 8 possible metabolites has been proposed.
Demethylation and hydroxylation were identified as the primary mechanisms of
biotransformation in vitro. The major metabolite identified in incubations with
human liver microsomes is 13-demethyl tacrolimus. In in vitro studies, a
31-demethyl metabolite has been reported to have the same activity as
tacrolimus.ExcretionThe mean clearance following IV administration of tacrolimus is
0.040, 0.083 and 0.053 L/hr/kg in healthy volunteers, adult kidney transplant
patients and adult liver transplant patients, respectively. In man, less than 1%
of the dose administered is excreted unchanged in urine.In a mass balance study of IV administered radiolabeled tacrolimus to 6
healthy volunteers, the mean recovery of radiolabel was 77.8 ± 12.7%. Fecal
elimination accounted for 92.4 ± 1.0% and the elimination half-life based on
radioactivity was 48.1 ± 15.9 hours whereas it was 43.5 ± 11.6 hours based on
tacrolimus concentrations. The mean clearance of radiolabel was 0.029 ± 0.015
L/hr/kg and clearance of tacrolimus was 0.029 ± 0.009 L/hr/kg.When administered PO, the mean recovery of the radiolabel was 94.9 ± 30.7%.
Fecal elimination accounted for 92.6 ± 30.7%, urinary elimination accounted for
2.3 ± 1.1% and the elimination half-life based on radioactivity was 31.9 ± 10.5
hours whereas it was 48.4 ± 12.3 hours based on tacrolimus concentrations. The
mean clearance of radiolabel was 0.226 ± 0.116 L/hr/kg and clearance of
tacrolimus 0.172 ± 0.088 L/hr/kg.Special PopulationsPediatricsIn a pharmacokinetic study of 14 pediatric atopic dermatitis
patients, between the ages of 2-5 years, peak blood concentrations of tacrolimus
ranged from undetectable to 14.8 ng/mL after single or multiple doses of 0.03%
PROTOPIC Ointment, with 86% (12/14) of patients having peak blood concentrations
below 2 ng/mL throughout the study. The highest peak concentration was observed in one patient with 82% BSA
involvement on day 1 following application of 0.03% PROTOPIC Ointment. The peak
concentrations for this subject were 14.8 ng/mL on day 1 and 4.1 ng/mL on day
14. Mean peak tacrolimus blood concentrations following oral administration in
pediatric liver transplant patients (n = 9) were 48.4± 27.9 ng/mL. In a similar pharmacokinetic study with 61 enrolled pediatric patients (ages
6 -12 years) with atopic dermatitis, peak tacrolimus blood concentrations ranged
from undetectable to 5.3 ng/mL after single or multiple doses of 0.1% PROTOPIC
Ointment, with 91% (52/57) of evaluable patients having peak blood
concentrations below 2 ng/mL throughout the study period. When detected,
systemic exposure generally declined as treatment continued. In clinical studies with periodic blood sampling, a similar distribution of
tacrolimus blood levels was also observed, with 98% (509/522) of pediatric
patients having a blood concentration below 2 ng/mL. Renal InsufficiencyThe effect of renal insufficiency on the pharmacokinetics of
topically administered tacrolimus has not been evaluated. The mean clearance of
IV administered tacrolimus in patients with renal dysfunction was similar to
that of normal volunteers. On the basis of this information dose-adjustment is
not expected to be needed.Hepatic InsufficiencyThe effect of hepatic insufficiency on the pharmacokinetics of
topically administered tacrolimus has not been evaluated but dose-adjustment is
not expected to be needed.

Clinical Studies

Three randomized, double-blind, vehicle-controlled, multi-center,
phase 3 studies were conducted to evaluate PROTOPIC Ointment for the treatment
of patients with moderate to severe atopic dermatitis. One (Pediatric) study
included 351 patients 2-15 years of age, and the other two (Adult) studies
included a total of 632 patients 15-79 years of age. Fifty-five percent (55%) of
the patients were women and 27% were black. At baseline, 58% of the patients had
severe disease and the mean body surface area (BSA) affected was 46%. Over 80%
of patients had atopic dermatitis affecting the face and/or neck region. In
these studies, patients applied either PROTOPIC Ointment 0.03%, PROTOPIC
Ointment 0.1%, or vehicle ointment twice daily to 10% - 100% of their BSA for up
to 12 weeks.In the pediatric study, a significantly greater (p less than 0.001) percentage of
patients achieved at least 90% improvement based on the physician’s global
evaluation of clinical response (the pre-defined primary efficacy endpoint) in
the PROTOPIC Ointment 0.03% treatment group compared to the vehicle treatment
group, but there was insufficient evidence that PROTOPIC Ointment 0.1% provided
more efficacy than PROTOPIC Ointment 0.03%. In both adult studies, a significantly greater (p less than 0.001) percentage of
patients achieved at least 90% improvement based on the physician’s global
evaluation of clinical response in the PROTOPIC Ointment 0.03% and PROTOPIC
Ointment 0.1% treatment groups compared to the vehicle treatment group. There
was evidence that PROTOPIC Ointment 0.1% may provide more efficacy than PROTOPIC
Ointment 0.03%. The difference in efficacy between PROTOPIC Ointment 0.1% and
0.03% was particularly evident in adult patients with severe disease at
baseline, adults with extensive BSA involvement, and black adults. Response
rates for each treatment group are shown below by age groups. Because the two
adult studies were identically designed, the results from these studies were
pooled in this table.Global Improvement over Baseline at the End-Of-Treatment in Three Phase
3 StudiesPhysician’s Global Evaluation of Clinical
Response (% Improvement)Pediatric Study (2-15 Years of Age)Adult
StudiesVehicleOintmentN = 116 PROTOPIC Ointment0.03%N = 117Vehicle OintmentN =
212PROTOPIC Ointment0.03%N = 211PROTOPIC Ointment0.1%N = 209 100%4 (3%)14 (12%)2 (1%)21 (10%)20 (10%)≥ 90%8 (7%)42 (36%)14 (7%)58 (28%)77 (37%)≥ 75%18 (16%)65 (56%)30 (14%)97 (46%)117 (56%)≥ 50%31 (27%)85 (73%)42 (20%)130 (62%)152 (73%) A statistically significant difference in the percentage of adult patients
with greater than or equal to 90% improvement was achieved by week 1 for those treated with PROTOPIC
Ointment 0.1%, and by week 3 for those treated with PROTOPIC Ointment 0.03%. A
statistically significant difference in the percentage of pediatric patients
with greater than or equal to 90% improvement was achieved by week 2 for those treated with PROTOPIC
Ointment 0.03%.In adult patients who had achieved greater than or equal to 90% improvement at the end of treatment,
35% of those treated with PROTOPIC Ointment 0.03% and 41% of those treated with
PROTOPIC Ointment 0.1%, regressed from this state of improvement at 2 weeks
after end-of-treatment. In pediatric patients who had achieved greater than or equal to 90%
improvement, 54% of those treated with PROTOPIC Ointment 0.03% regressed from
this state of improvement at 2 weeks after end-of-treatment. Because patients
were not followed for longer than 2 weeks after end-of-treatment, it is not
known how many additional patients regressed at periods longer than 2 weeks
after cessation of therapy. In both PROTOPIC Ointment treatment groups in adults and in the PROTOPIC
Ointment 0.03% treatment group in pediatric patients, a significantly greater
improvement compared to vehicle (p less than 0.001) was observed in the secondary
efficacy endpoints of percent body surface area involved, patient evaluation of
pruritus, erythema, edema, excoriation, oozing, scaling, and lichenification.
The following two graphs depict the time course of improvement in the percent
body surface area affected in adult and in pediatric patients as a result of
treatment.Figure 1 - Adult Patients Body Surface Area Over TimeFigure 2 – Pediatric Patients Body Surface Area Over
TimeThe following two graphs depict the time course of improvement in erythema in
adult and in pediatric patients as a result of treatment.Figure 3 - Adult Patients Mean Erythema Over TimeFigure 4 - Pediatric Patients Mean Erythema Over
TimeThe time course of improvement in the remaining secondary efficacy variables
was similar to that of erythema, with improvement in lichenification slightly
slower.

Indications And Usage

PROTOPIC Ointment, both 0.03% and 0.1% for adults, and only 0.03%
for children aged 2 to 15 years, is indicated as second-line
therapy  for the short-term and non-continuous chronic treatment of
moderate to severe atopic dermatitis in non-immunocompromised adults and
children who have failed to respond adequately to other topical prescription
treatments for atopic dermatitis, or when those treatments are not
advisable.PROTOPIC Ointment is not indicated for children younger than
2 years of age (see boxed WARNING, WARNINGS and PRECAUTIONS:
Pediatric
Use).

Contraindications

PROTOPIC (tacrolimus) Ointment is contraindicated in patients with a history of
hypersensitivity to tacrolimus or any other component of the ointment.

Warnings

  • WARNINGLong-term Safety of Topical Calcineurin Inhibitors Has Not
  • Been EstablishedAlthough a causal relationship has not been established, rare cases of
  • Malignancy (e.g., skin and lymphoma) have been reported in patients treated with
  • Topical calcineurin inhibitors, including PROTOPIC Ointment. Therefore:Continuous long-term use of topical calcineurin inhibitors, including
  • PROTOPIC Ointment, in any age group should be avoided, and application limited
  • To areas of involvement with atopic dermatitis.PROTOPIC Ointment is not indicated for use in children less than 2 years of
  • Age. Only 0.03% PROTOPIC Ointment is indicated for use in children 2-15 years of
  • Age. Prolonged systemic use of calcineurin inhibitors for sustained
  • Immunosuppression in animal studies and transplant patients following systemic
  • Administration has been associated with an increased risk of infections,
  • Lymphomas, and skin malignancies. These risks are associated with the intensity
  • And duration of immunosuppression.Based on the information above and the mechanism of action, there is a
  • Concern about potential risk with the use of topical calcineurin inhibitors,
  • Including PROTOPIC Ointment. While a causal relationship has not been
  • Established, rare cases of skin malignancy and lymphoma have been reported in
  • Patients treated with topical calcineurin inhibitors, including PROTOPIC
  • Ointment. Therefore: PROTOPIC Ointment should not be used in immunocompromised adults and
  • Children.If signs and symptoms of atopic dermatitis do not improve within 6 weeks,
  • Patients should be re-examined by their healthcare provider and their diagnosis
  • Be confirmed (see PRECAUTIONS: General).The safety of PROTOPIC Ointment has not been established beyond one year of
  • Non-continuous use.(See CLINICAL
  • PHARMACOLOGY, boxed WARNINGS,
  • INDICATIONS AND
  • USAGE, and DOSAGE AND
  • ADMINISTRATION).

Precautions

  • GeneralThe use of PROTOPIC Ointment should be avoided on pre-malignant
  • And malignant skin conditions. Some malignant skin conditions, such as cutaneous
  • T-cell lymphoma (CTCL), may mimic atopic dermatitis. The use of PROTOPIC Ointment in patients with Netherton’s Syndrome or other
  • Skin diseases where there is the potential for increased systemic absorption of
  • Tacrolimus is not recommended. The safety of PROTOPIC Ointment has not been
  • Established in patients with generalized erythroderma.The use of PROTOPIC Ointment may cause local symptoms such as skin burning
  • (burning sensation, stinging, soreness) or pruritus. Localized symptoms are most
  • Common during the first few days of PROTOPIC Ointment application and typically
  • Improve as the lesions of atopic dermatitis resolve. With PROTOPIC Ointment
  • 0.1%, 90% of the skin burning events had a duration between 2 minutes and 3
  • Hours (median 15 minutes). 90% of the pruritus events had a duration between 3
  • Minutes and 10 hours (median 20 minutes). (see ADVERSE
  • REACTIONS). Bacterial and Viral Skin InfectionsBefore commencing treatment with PROTOPIC Ointment, cutaneous
  • Bacterial or viral infections at treatment sites should be resolved. Studies
  • Have not evaluated the safety and efficacy of PROTOPIC Ointment in the treatment
  • Of clinically infected atopic dermatitis. While patients with atopic dermatitis are predisposed to superficial skin
  • Infections including eczema herpeticum (Kaposi’s varicelliform eruption),
  • Treatment with PROTOPIC Ointment may be independently associated with an
  • Increased risk of varicella zoster virus infection (chicken pox or shingles),
  • Herpes simplex virus infection, or eczema herpeticum. Patients with LymphadenopathyIn clinical studies, 112/13494 (0.8%) cases of lymphadenopathy
  • Were reported and were usually related to infections (particularly of the skin)
  • And noted to resolve upon appropriate antibiotic therapy. Of these 112 cases,
  • The majority had either a clear etiology or were known to resolve. Transplant
  • Patients receiving immunosuppressive regimens (e.g., systemic tacrolimus) are at
  • Increased risk for developing lymphoma; therefore, patients who receive PROTOPIC
  • Ointment and who develop lymphadenopathy should have the etiology of their
  • Lymphadenopathy investigated. In the absence of a clear etiology for the
  • Lymphadenopathy, or in the presence of acute infectious mononucleosis, PROTOPIC
  • Ointment should be discontinued. Patients who develop lymphadenopathy should be
  • Monitored to ensure that the lymphadenopathy resolves. Sun ExposureDuring the course of treatment, patients should minimize or avoid
  • Natural or artificial sunlight exposure, even while PROTOPIC is not on the skin.
  • It is not known whether PROTOPIC Ointment interferes with skin response to
  • Ultraviolet damage. Immunocompromised PatientsThe safety and efficacy of PROTOPIC Ointment in immunocompromised
  • Patients have not been studied.Renal Insufficiency Rare post-marketing cases of acute renal failure have been
  • Reported in patients treated with PROTOPIC Ointment. Systemic absorption is more
  • Likely to occur in patients with epidermal barrier defects especially when
  • PROTOPIC is applied to large body surface areas. Caution should also be
  • Exercised in patients predisposed to renal impairment.Information for Patients(See Medication
  • Guide) Patients using PROTOPIC Ointment should receive and understand the
  • Information in the Medication Guide. Please refer to the Medication Guide for
  • Providing instruction and information to the patient.What is the most important information patients should know
  • About PROTOPIC Ointment? The safety of using PROTOPIC Ointment for a long period of time is not known.
  • A very small number of people who have used PROTOPIC Ointment have had cancer
  • (for example, skin or lymphoma). However, a link with PROTOPIC Ointment has not
  • Been shown. Because of this concern, instruct patients:Do not use PROTOPIC Ointment continuously for a long time.Use PROTOPIC Ointment only on areas of skin that have eczema.Do not use PROTOPIC Ointment on a child under 2 years old.PROTOPIC Ointment comes in two strengths:Only PROTOPIC Ointment 0.03% is for use on children aged 2 to 15 years.Either PROTOPIC Ointment 0.03% or 0.1% can be used by adults and children 16
  • Years and older.Advise patients to talk to their prescriber for more information.How should PROTOPIC Ointment be used?Advise patients to:Use PROTOPIC Ointment exactly as prescribed. Use PROTOPIC Ointment only on areas of skin that have eczema.Use PROTOPIC Ointment for short periods, and if needed, treatment may be
  • Repeated with breaks in between.Stop PROTOPIC Ointment when the signs and symptoms of eczema, such as
  • Itching, rash, and redness go away, or as directed.Follow their doctor’s advice if symptoms of eczema return after treatment
  • With PROTOPIC Ointment.Call their doctor if:
  • Their symptoms get worse with PROTOPIC Ointment.They get an infection on their skin.Their symptoms do not improve after 6 weeks of treatment. Sometimes other
  • Skin diseases can look like eczema.To apply PROTOPIC Ointment:Advise patients:Wash their hands before applying PROTOPIC.Apply a thin layer of PROTOPIC Ointment twice daily to the areas of skin
  • Affected by eczema.Use the smallest amount of PROTOPIC Ointment needed to control the signs and
  • Symptoms of eczema.If they are a caregiver applying PROTOPIC Ointment to a patient, or if they
  • Are a patient who is not treating their hands, wash their hands with soap and
  • Water after applying PROTOPIC. This should remove any ointment left on the
  • Hands.Do not bathe, shower, or swim right after applying PROTOPIC. This could wash
  • Off the ointment.Moisturizers can be used with PROTOPIC Ointment. Make sure they check with
  • Their doctor first about the products that are right for them. Because the skin
  • Of patients with eczema can be very dry, it is important to keep up good skin
  • Care practices. If they use moisturizers, apply them after PROTOPIC
  • Ointment.What should patients avoid while using PROTOPIC
  • Ointment?Advise patients:Do not use ultraviolet light therapy, sun lamps, or tanning beds during
  • Treatment with PROTOPIC Ointment.Limit sun exposure during treatment with PROTOPIC Ointment even when the
  • Medicine is not on their skin. If patients need to be outdoors after applying
  • PROTOPIC Ointment, wear loose fitting clothing that protects the treated area
  • From the sun. Doctors should advise what other types of protection from the sun
  • Patients should use.Do not cover the skin being treated with bandages, dressings or wraps.
  • Patients can wear normal clothing.Avoid getting PROTOPIC Ointment in the eyes or mouth. Do not swallow
  • PROTOPIC Ointment. Patients should call their doctor if they swallow PROTOPIC
  • Ointment.Drug InteractionsFormal 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 (see CLINICAL
  • PHARMACOLOGY). 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.Carcinogenesis, Mutagenesis, Impairment of
  • FertilityNo evidence of genotoxicity was seen in bacterial (Salmonella and E. coli) or
  • Mammalian (Chinese hamster lung-derived cells) in
  • Vitro assays of mutagenicity, the in vitro
  • CHO/HGPRT assay of mutagenicity, or in vivo
  • Clastogenicity assays performed in mice. Tacrolimus did not cause unscheduled
  • DNA synthesis in rodent hepatocytes.Oral (feed) carcinogenicity studies have been carried out with systemically
  • Administered tacrolimus in male and female rats and mice. In the 80-week mouse
  • Study and in the 104-week rat study no relationship of tumor incidence to
  • Tacrolimus dosage was found at daily doses up to 3 mg/kg [9X the Maximum
  • Recommended Human Dose (MRHD) based on AUC comparisons] and 5 mg/kg (3X the MRHD
  • Based on AUC comparisons), respectively. A 104-week dermal carcinogenicity study was performed in mice with tacrolimus
  • Ointment (0.03% - 3%), equivalent to tacrolimus doses of 1.1-118 mg/kg/day or
  • 3.3-354 mg/m2/day. In the study, the incidence of skin
  • Tumors was minimal and the topical application of tacrolimus was not associated
  • With skin tumor formation under ambient room lighting. However, a statistically
  • Significant elevation in the incidence of pleomorphic lymphoma in high dose male
  • (25/50) and female animals (27/50) and in the incidence of undifferentiated
  • Lymphoma in high dose female animals (13/50) was noted in the mouse dermal
  • Carcinogenicity study. Lymphomas were noted in the mouse dermal carcinogenicity
  • Study at a daily dose of 3.5 mg/kg (0.1% tacrolimus ointment) (26X MRHD based on
  • AUC comparisons). No drug-related tumors were noted in the mouse dermal
  • Carcinogenicity study at a daily dose of 1.1 mg/kg (0.03% tacrolimus ointment)
  • (10X MRHD based on AUC comparisons). In a 52-week photocarcinogenicity study, the median time to onset of skin
  • Tumor formation was decreased in hairless mice following chronic topical dosing
  • With concurrent exposure to UV radiation (40 weeks of treatment followed by 12
  • Weeks of observation) with tacrolimus ointment at ≥0.1% tacrolimus. Reproductive toxicology studies were not performed with topical tacrolimus.
  • In studies of oral tacrolimus no impairment of fertility was seen in male and
  • Female rats. Tacrolimus, given orally at 1.0 mg/kg (0.12X MRHD based on body
  • Surface area [BSA]) to male and female rats, prior to and during mating, as well
  • As to dams during gestation and lactation, was associated with embryolethality
  • And with adverse effects on female reproduction. Effects on female reproductive
  • Function (parturition) and embryolethal effects were indicated by a higher rate
  • Of pre-implantation loss and increased numbers of undelivered and nonviable
  • Pups. When given at 3.2 mg/kg (0.43X MRHD based on BSA), tacrolimus was
  • Associated with maternal and paternal toxicity as well as reproductive toxicity
  • Including marked adverse effects on estrus cycles, parturition, pup viability,
  • And pup malformations. Pregnancy Teratogenic Effects: Pregnancy
  • Category CThere are no adequate and well-controlled studies of topically
  • Administered tacrolimus in pregnant women. The experience with PROTOPIC Ointment
  • When used by pregnant women is too limited to permit assessment of the safety of
  • Its use during pregnancy.Reproduction studies were carried out with systemically administered
  • Tacrolimus in rats and rabbits. Adverse effects on the fetus were observed
  • Mainly at oral dose levels that were toxic to dams. Tacrolimus at oral doses of
  • 0.32 and 1.0 mg/kg (0.04X-0.12X MRHD based on BSA) during organogenesis in
  • Rabbits was associated with maternal toxicity as well as an increase in
  • Incidence of abortions. At the higher dose only, an increased incidence of
  • Malformations and developmental variations was also seen. Tacrolimus, at oral
  • Doses of 3.2 mg/kg during organogenesis in rats, was associated with maternal
  • Toxicity and caused an increase in late resorptions, decreased numbers of live
  • Births, and decreased pup weight and viability. Tacrolimus, given orally at 1.0
  • And 3.2 mg/kg (0.04X-0.12X MRHD based on BSA) to pregnant rats after
  • Organogenesis and during lactation, was associated with reduced pup weights.No reduction in male or female fertility was evident. There are no adequate and well-controlled studies of systemically
  • Administered tacrolimus in pregnant women. Tacrolimus is transferred across the
  • Placenta. The use of systemically administered tacrolimus during pregnancy has
  • Been associated with neonatal hyperkalemia and renal dysfunction. PROTOPIC
  • Ointment should be used during pregnancy only if the potential benefit to the
  • Mother justifies a potential risk to the fetus.Nursing MothersAlthough systemic absorption of tacrolimus following topical
  • Applications of PROTOPIC Ointment is minimal relative to systemic
  • Administration, it is known that tacrolimus is excreted in human milk. Because
  • Of the potential for serious adverse reactions in nursing infants from
  • Tacrolimus, a decision should be made whether to discontinue nursing or to
  • Discontinue the drug, taking into account the importance of the drug to the
  • Mother. Pediatric UsePROTOPIC Ointment is not indicated for children
  • Less than 2 years of age. Only the lower concentration, 0.03%, of PROTOPIC Ointment is recommended for
  • Use as a second-line therapy for short-term and
  • Non-continuous chronic treatment of moderate to severe atopic dermatitis in
  • Non-immunocompromised children 2 to 15 years of age who have failed to respond
  • Adequately to other topical prescription treatments for atopic dermatitis, or
  • When those treatments are not advisable. The long-term safety and effects of PROTOPIC Ointment on the developing
  • Immune system are unknown (see boxed WARNING, WARNINGS
  • And INDICATIONS and
  • USAGE).Four studies were conducted involving a total of about 4,400 patients 2-15
  • Years of age: one 12-week randomized vehicle-controlled study and three
  • Open-label safety studies of one to three years duration. About 2,500 of these
  • Patients were 2 to 6 years of age. The most common adverse events from these studies associated with PROTOPIC
  • Ointment application in pediatric patients were skin burning and pruritus (see
  • ADVERSE
  • REACTIONS). In addition to skin burning and pruritus, the less common
  • Events (less than 5%) of varicella zoster (mostly chicken pox), and vesiculobullous
  • Rash were more frequent in patients treated with PROTOPIC Ointment 0.03%
  • Compared to vehicle. In the open-label safety studies, the incidence of adverse
  • Events, including infections, did not increase with increased duration of study
  • Drug exposure or amount of ointment used. In about 4,400 pediatric patients
  • Treated with PROTOPIC Ointment, 24 (0.5%) were reported with eczema herpeticum.
  • Since the safety and efficacy of PROTOPIC Ointment have not been established in
  • Pediatric patients below 2 years of age, its use in this age group is not
  • Recommended. In an open-label study, immune response to a 23-valent pneumococcal
  • Polysaccharide vaccine was assessed in 23 children 2 to 12 years old with
  • Moderate to severe atopic dermatitis treated with tacrolimus ointment 0.03%.
  • Protective antibody titers developed in all patients. Similarly, in a
  • Seven-month, double-blind trial, the vaccination response to meningococcal
  • Serogroup C was equivalent in children 2 to 11 years old with moderate to severe
  • Atopic dermatitis treated with tacrolimus ointment 0.03% (n=121), a
  • Hydrocortisone ointment regimen (n=111), or normal children (n=44). Geriatric UseFour hundred and four (404) patients ≥ 65 years old received
  • PROTOPIC Ointment in phase 3 studies. The adverse event profile for these
  • Patients was consistent with that for other adult patients.

Adverse Reactions

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 StudiesTime
on StudyAdultPediatricsTotalless than 1 year468244819163greater than or equal to 1 year118513492534greater than or equal to 2 years200275475greater than or equal to 3 years118182300The 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-Blink, Phase 3 Studies                                  Open-Label Studies (up to 3 years)                                                                                                                                0.1% and 0.03% Tacrolimus         12-Week Adjusted Incidence Rate (%)                                                        Ointment Incidence Rate (%)                                                                   Adult Pediatric Adult Pediatric TotalVehicle(n=212)%0.03%TacrolimusOintment(n=210)%0.1%TacrolimusOintment(n=209)%Vehicle(n=116)%0.03%TacrolimusOintment(n=118)%(n-4682)%(n=4481)%(n=9163)%Skin Burning*2646582943282024Pruritus*3746462741251922Flue-likesymptoms*1923312528223428Allergic Reaction81268491311Skin Erythema20252813121279Headache*1120198513911Skin Infection11125141091612Fever44113212148Infection112976108Cough Increased21114183106Asthma464664138Herpes Simplex44420433EczemaHerpeticum01102000Pharyngitis3341164128Accidental Injury43636687Pustular Rash23432275Folliculitis*16402423Rhinitis43226243Otis Media4016122116Sinusitis*14283676Diarrhea33425243Urticaria33611344Lack of DrugEffect11011666Bronchitis02233444Vomiting01176143MaculopapularRash22230211Rash*15242233Abdominal Pain31123132Fungal Dermatitis02130243Gastroentesritis12230243AlcoholIntolerance*03700402Acne*24710323Sunburn12100211Skin Disorder22114222Conjunctivitis02221333Pain12101212VesiculobullousRash*33204211Lymphadenopathy22103121Nausea43201212Skin Tingling*23812211Face Edema22121111Dyspepsia*11400222Dry Skin73301111Hypersthesia*13700201Skin NeoplasmBenign†11100122Back Pain*02211302Peripheral Edema24300201Varicella Zoster/HerpesZoster*‡01005122Contact Dermatitis13334222Asthena12300101Pneumonia01120132Eczema22200101Insomnia34311201Exfoliative Dermatitis33100010Dysmenorrhea24400211PeriodontalAbscess10100111Myalgia*03200211Cyst*01300101Cellulitis11100111Exacerbation ofUntreated Area10110111ProceduralComplication10010111Hypertension00100201Tooth Disorder01110211Arthralgia11320212Depression12100101Paresthesia13300212Alopecia01100111Urinary Tract Infection00100212Ear Pain10101011*   May be reasonably associated with the use of this drug product†    Generally "warts".‡    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.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.CNSSeizuresNeoplasmsLymphomas, basal cell carcinoma, squamous cell carcinoma, malignant
melanomaInfectionsBullous impetigo, osteomyelitis, septicemiaRenalAcute renal failure in patients with or without Netherton’s syndrome, renal
impairmentSkinRosacea

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.

Dosage And Administration

  • AdultPROTOPIC Ointment 0.03% and 0.1%Apply a thin layer of PROTOPIC (tacrolimus) Ointment to the affected skin
  • Twice daily. The minimum amount should be rubbed in gently and completely to
  • Control signs and symptoms of atopic dermatitis. Stop using when signs and
  • Symptoms of atopic dermatitis resolve. If signs and symptoms (e.g. itch, rash, and redness) do not improve within 6
  • Weeks, patients should be re-examined by their healthcare provider to confirm
  • The diagnosis of atopic dermatitis. Continuous long-term use of topical calcineurin inhibitors, including
  • PROTOPIC Ointment should be avoided, and application should be limited to areas
  • Of involvement with atopic dermatitis. The safety of PROTOPIC Ointment under occlusion, which may promote systemic
  • Exposure, has not been evaluated. PROTOPIC Ointment should not be used with
  • Occlusive dressings.PEDIATRIC – FOR CHILDREN 2-15 YEARS PROTOPIC Ointment 0.03%Apply a thin layer of PROTOPIC (tacrolimus) Ointment, 0.03% to the affected
  • Skin twice daily. The minimum amount should be rubbed in gently and completely
  • To control signs and symptoms of atopic dermatitis. Stop using when signs and
  • Symptoms of atopic dermatitis resolve. If signs and symptoms (e.g. itch, rash, and redness) do not improve within 6
  • Weeks, patients should be re-examined by their healthcare provider to confirm
  • The diagnosis of atopic dermatitis. Continuous long-term use of topical calcineurin inhibitors, including
  • PROTOPIC Ointment should be avoided, and application should be limited to areas
  • Of involvement with atopic dermatitis. The safety of PROTOPIC Ointment under occlusion, which may promote systemic
  • Exposure, has not been evaluated. PROTOPIC Ointment should not be used with
  • Occlusive dressings.

How Supplied

PROTOPIC® (tacrolimus) Ointment
0.1%NDC54868-5233-1        30 gram laminate tubeNDC 54868-5233-0     100 gram laminate tubeStore at room temperature 25°C (77°F); excursions permitted to 15°-30°C
(59°-86°F).Marketed by:Astellas Pharma US, Inc.Deerfield, IL 60015-2548Manufactured by:Astellas Toyama Co., Ltd.  Toyama Plant, 2-178 Kojin-machi, Toyama 930-0809,
JapanRelabeling of "Additional Barcode" by:Physicians Total Care, Inc.Tulsa, OK      74146

Medication Guide

  • PROTOPIC®  [pro-TOP-ik](tacrolimus)Ointment 0.03%Ointment 0.1%Read the Medication Guide every time you or a family member gets PROTOPIC
  • Ointment. There may be new information. This Medication Guide does not take the
  • Place of talking to your doctor about your medical condition or treatment. If
  • You have questions about PROTOPIC Ointment, ask your doctor or
  • Pharmacist.What is the most important information I should know about
  • PROTOPIC Ointment? The safety of using PROTOPIC Ointment for a long period of time is not known.
  • A very small number of people who have used PROTOPIC Ointment have had cancer
  • (for example, skin or lymphoma). However, a link with PROTOPIC Ointment has not
  • Been shown. Because of this concern:Do not use PROTOPIC Ointment continuously for a long time.Use PROTOPIC Ointment only on areas of your skin that have eczema.Do not use PROTOPIC Ointment on a child under 2 years old.PROTOPIC Ointment comes in two strengths:Only PROTOPIC Ointment 0.03% is for use on children aged 2 to 15 years.Either PROTOPIC Ointment 0.03% or 0.1% can be used by adults and children 16
  • Years and older.Talk to your doctor for more information.What is PROTOPIC Ointment?PROTOPIC Ointment is a prescription medicine used on the skin (topical) to
  • Treat eczema (atopic dermatitis). PROTOPIC Ointment is in a class of medicines
  • Called topical calcineurin inhibitors. It is for adults and children 2 years of
  • Age and older who do not have a weakened immune system. PROTOPIC Ointment is
  • Used on the skin for short periods, and if needed, treatment may be repeated
  • With breaks in between.PROTOPIC Ointment is for use after other prescription medicines have not
  • Worked for you, or if your doctor recommends that other prescription medicines
  • Should not be used.Who should not use PROTOPIC Ointment?PROTOPIC Ointment should not be used:on children younger than 2 years of age.if you are allergic to PROTOPIC Ointment or anything in it. See the end of
  • This Medication Guide for a complete list of ingredients.What should I tell my doctor before starting PROTOPIC
  • Ointment?Before you start using PROTOPIC, you and your doctor should talk about all of
  • Your medical conditions, including if you:have a skin disease called Netherton’s syndrome (a rare inherited
  • Condition).have any infection on your skin including chicken pox or herpes.have been told you have a weakened immune system.are pregnant, breastfeeding, or planning to become pregnant.Tell your doctor about all the medicines you take and skin products you use
  • Including prescription and nonprescription medicines, vitamins, and herbal
  • Supplements.Know the medicines you take. Keep a list of them with you to show your doctor
  • And pharmacist each time you get a new medicine.How should I use PROTOPIC Ointment?Use PROTOPIC Ointment exactly as prescribed. Use PROTOPIC Ointment only on areas of your skin that have eczema.Use PROTOPIC Ointment for short periods, and if needed, treatment may be
  • Repeated with breaks in between.Stop PROTOPIC Ointment when the signs and symptoms of eczema, such as
  • Itching, rash, and redness go away, or as directed by your doctor.Follow your doctor’s advice if symptoms of eczema return after treatment
  • With PROTOPIC Ointment.Call your doctor if :
  • Your symptoms get worse with PROTOPIC Ointment.you get an infection on your skin.your symptoms do not improve after 6 weeks of treatment. Sometimes other
  • Skin diseases can look like eczema.To apply PROTOPIC Ointment:Wash your hands before applying PROTOPIC.Apply a thin layer of PROTOPIC Ointment twice daily to the areas of skin
  • Affected by eczema.Use the smallest amount of PROTOPIC Ointment needed to control the signs and
  • Symptoms of eczema.If you are a caregiver applying PROTOPIC Ointment to a
  • Patient, or if you are a patient who is not treating your hands, wash your hands
  • With soap and water after applying PROTOPIC. This should remove any ointment
  • Left on the hands.Do not bathe, shower, or swim right after applying PROTOPIC. This could wash
  • Off the ointment.You can use moisturizers with PROTOPIC Ointment. Make sure you check with
  • Your doctor first about the products that are right for you. Because the skin of
  • Patients with eczema can be very dry, it is important to keep up good skin care
  • Practices. If you use moisturizers, apply them after PROTOPIC
  • Ointment.What should I avoid while using PROTOPIC Ointment?Do not use ultraviolet light therapy, sun lamps, or tanning beds during
  • Treatment with PROTOPIC Ointment.Limit sun exposure during treatment with PROTOPIC Ointment even when the
  • Medicine is not on your skin. If you need to be outdoors after applying PROTOPIC
  • Ointment, wear loose fitting clothing that protects the treated area from the
  • Sun. Ask your doctor what other types of protection from the sun you should
  • Use.Do not cover the skin being treated with bandages, dressings or wraps. You
  • Can wear normal clothing.Avoid getting PROTOPIC Ointment in the eyes or mouth. Do not swallow
  • PROTOPIC Ointment. If you do, call your doctor.What are the possible side effects of PROTOPIC
  • Ointment?Please read the first section of this Medication
  • Guide.The most common side effects of PROTOPIC Ointment at
  • The skin application site are stinging, burning, or itching of the skin treated
  • With PROTOPIC. These side effects are usually mild to moderate, are most common
  • During the first few days of treatment, and usually go away as your skin
  • Heals.Other side effects include acne, swollen or infected
  • Hair follicles, headache, increased sensitivity of the skin to hot or cold
  • Temperatures, or flu-like symptoms such as the common cold and stuffy nose, skin
  • Tingling, upset stomach, muscle pain, swollen glands (enlarged lymph nodes), or
  • Skin infections including cold sores, chicken pox or shingles.Talk to your doctor if you have a skin infection or if side effects (for
  • Example, swollen glands) continue or bother you.While you are using PROTOPIC, drinking alcohol may cause the skin or face to
  • Become flushed or red and feel hot. These are not all the side effects with PROTOPIC Ointment. Ask your doctor or
  • Pharmacist for more information.Call your doctor for medical advice about side effects. You may report side
  • Effects to FDA at 1-800-FDA-1088How should I store PROTOPIC Ointment?Store PROTOPIC Ointment at room temperature (59° to 86°F). Do not leave
  • PROTOPIC Ointment in your car in cold or hot weather. Make sure the cap on the
  • Tube is tightly closed.Keep PROTOPIC Ointment and all medicines out of the reach
  • Of children.General advice about PROTOPIC OintmentMedicines are sometimes prescribed for purposes other than those listed in a
  • Medication Guide. Do not use PROTOPIC Ointment for a condition for which it was
  • Not prescribed. Do not give PROTOPIC Ointment to other people, even if they have
  • The same symptoms you have. It may not be right for them.This Medication Guide summarizes the most important information about
  • PROTOPIC Ointment. If you would like more information, talk with your
  • Doctor.Your doctor or pharmacist can give you information about PROTOPIC Ointment
  • That is written for health care professionals. For more information, you can
  • Also visit the PROTOPIC website at www.protopic.com or call
  • 1-800-727-7003.What are the ingredients in PROTOPIC Ointment?Active Ingredient: tacrolimus, either 0.03% or
  • 0.1%Inactive Ingredients: mineral oil, paraffin,
  • Propylene carbonate, white petrolatum and white wax.Marketed by:Astellas Pharma US, Inc.Deerfield, IL 60015-2548Manufactured by:Astellas Toyama Co., Ltd.  Toyama Plant, 2-178 Kojin-machi, Toyama 930-0809,
  • JapanThis Medication Guide has been approved by the U.S. Food and Drug
  • AdministrationRevised: June 200909F001-PRT-CPI

* Please review the disclaimer below.