PIMECROLIMUS cream

Country: United States

Language: English

Source: NLM (National Library of Medicine)

Active ingredient:

PIMECROLIMUS (UNII: 7KYV510875) (PIMECROLIMUS - UNII:7KYV510875)

Available from:

Bryant Ranch Prepack

Administration route:

TOPICAL

Prescription type:

PRESCRIPTION DRUG

Therapeutic indications:

Pimecrolimus Cream, 1% is indicated as second-line therapy for the short-term and non-continuous chronic treatment of mild to moderate atopic dermatitis in non-immunocompromised adults and children 2 years of age and older, who have failed to respond adequately to other topical prescription treatments, or when those treatments are not advisable. Pimecrolimus Cream, 1% is not indicated for use in children less than 2 years of age [see Warnings and Precautions (5.1), Use in Specific Populations (8.4)] . Pimecrolimus Cream, 1% is contraindicated in individuals with a history of hypersensitivity to pimecrolimus or any of the components of the cream. There are no adequate and well-controlled studies with Pimecrolimus Cream, 1% in pregnant women. Therefore, Pimecrolimus Cream, 1% should be used during pregnancy only if the potential benefit justifies the potential risk to the fetus. In dermal embryofetal developmental studies, no maternal or fetal toxicity was observed up to the highest practicable doses tested, 10 mg/kg/day (1% pimecrolimus cream) in rats (0.14X MRHD based on body surface area) and 10 mg/kg/day (1% pimecrolimus cream) in rabbits (0.65X MRHD based on AUC comparisons). The 1% pimecrolimus cream was administered topically for 6 hours/day during the period of organogenesis in rats and rabbits (gestational days 6-21 in rats and gestational days 6-20 in rabbits). A second dermal embryofetal development study was conducted in rats using pimecrolimus cream applied dermally to pregnant rats (1 g cream/kg body weight of 0.2%, 0.6% and 1.0% pimecrolimus cream) from gestation day 6 to 17 at doses of 2, 6, and 10 mg/kg/day with daily exposure of approximately 22 hours. No maternal, reproductive, or embryofetal toxicity attributable to pimecrolimus was noted at 10 mg/kg/day (0.66X MRHD based on AUC comparisons), the highest dose evaluated in this study. No teratogenicity was noted in this study at any dose. A combined oral fertility and embryofetal developmental study was conducted in rats and an oral embryofetal developmental study was conducted in rabbits. Pimecrolimus was administered during the period of organogenesis (2 weeks prior to mating until gestational day 16 in rats, gestational days 6-18 in rabbits) up to dose levels of 45 mg/kg/day in rats and 20 mg/kg/day in rabbits. In the absence of maternal toxicity, indicators of embryofetal toxicity (post-implantation loss and reduction in litter size) were noted at 45 mg/kg/day (38X MRHD based on AUC comparisons) in the oral fertility and embryofetal developmental study conducted in rats. No malformations in the fetuses were noted at 45 mg/kg/day (38X MRHD based on AUC comparisons) in this study. No maternal toxicity, embryotoxicity or teratogenicity were noted in the oral rabbit embryofetal developmental toxicity study at 20 mg/kg/day (3.9X MRHD based on AUC comparisons), which was the highest dose tested in this study. A second oral embryofetal development study was conducted in rats. Pimecrolimus was administered during the period of organogenesis (gestational days 6 – 17) at doses of 2, 10 and 45 mg/kg/day. Maternal toxicity, embryolethality and fetotoxicity were noted at 45 mg/kg/day (271X MRHD based on AUC comparisons). A slight increase in skeletal variations that were indicative of delayed skeletal ossification was also noted at this dose. No maternal toxicity, embryolethality or fetotoxicity were noted at 10 mg/kg/day (16X MRHD based on AUC comparisons). No teratogenicity was noted in this study at any dose. A second oral embryofetal development study was conducted in rabbits. Pimecrolimus was administered during the period of organogenesis (gestational days 7 – 20) at doses of 2, 6 and 20 mg/kg/day. Maternal toxicity, embryotoxicity and fetotoxicity were noted at 20 mg/kg/day (12X MRHD based on AUC comparisons). A slight increase in skeletal variations that were indicative of delayed skeletal ossification was also noted at this dose. No maternal toxicity, embryotoxicity or fetotoxicity were noted at 6 mg/kg/day (5X MRHD based on AUC comparisons). No teratogenicity was noted in this study at any dose. An oral peri- and postnatal developmental study was conducted in rats. Pimecrolimus was administered from gestational day 6 through lactational day 21 up to a dose level of 40 mg/kg/day. Only 2 of 22 females delivered live pups at the highest dose of 40 mg/kg/day. Postnatal survival, development of the F1 generation, their subsequent maturation and fertility were not affected at 10 mg/kg/day (12X MRHD based on AUC comparisons), the highest dose evaluated in this study. Pimecrolimus was transferred across the placenta in oral rat and rabbit embryofetal developmental studies. It is not known whether this drug is excreted in human milk. Because of the potential for serious adverse reactions in nursing infants from pimecrolimus, 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. Pimecrolimus Cream, 1% is not indicated for use in children less than 2 years of age. The long-term safety and effects of Pimecrolimus Cream, 1% on the developing immune system are unknown. Three Phase 3 pediatric trials were conducted involving 1114 subjects 2-17 years of age. Two trials were 6-week randomized vehicle-controlled trials with a 20-week open-label phase and one was a vehicle-controlled (up to 1 year) safety trial with the option for sequential topical corticosteroid use. Of these subjects, 542 (49%) were 2-6 years of age. In the short-term trials, 11% of Pimecrolimus subjects did not complete these trials and 1.5% of Pimecrolimus subjects discontinued due to adverse events. In the 1-year trial, 32% of Pimecrolimus subjects did not complete this trial and 3% of Pimecrolimus subjects discontinued due to adverse events. Most discontinuations were due to unsatisfactory therapeutic effect. The most common local adverse event in the short-term trials of Pimecrolimus Cream, 1% in pediatric subjects ages 2-17 was application site burning (10% vs. 13% vehicle); the incidence in the long-term trial was 9% Pimecrolimus vs. 7% vehicle [see Adverse Reactions (6.1)] . Adverse events that were more frequent (>5%) in subjects treated with Pimecrolimus Cream, 1% compared to vehicle were headache (14% vs. 9%) in the short-term trial. Nasopharyngitis (26% vs. 21%), influenza (13% vs. 4%), pharyngitis (8% vs. 3%), viral infection (7% vs. 1%), pyrexia (13% vs. 5%), cough (16% vs. 11%), and headache (25% vs. 16%) were increased over vehicle in the 1-year safety trial [see Adverse Reactions (6.1)] . In 843 subjects ages 2-17 years treated with Pimecrolimus Cream, 1%, 9 (0.8%) developed eczema herpeticum (5 on Pimecrolimus Cream, 1% alone and 4 on Pimecrolimus Cream, 1% used in sequence with corticosteroids). In 211 subjects on vehicle alone, there were no cases of eczema herpeticum. The majority of adverse events were mild to moderate in severity. Two Phase 3 trials were conducted involving 436 infants age 3 months-23 months. One 6-week randomized vehicle-controlled trial with a 20-week open-label phase and one safety trial, up to one year, were conducted. In the 6-week trial, 11% of Pimecrolimus and 48% of vehicle subjects did not complete this trial; no subject in either group discontinued due to adverse events. Infants on Pimecrolimus Cream, 1% had an increased incidence of some adverse events compared to vehicle. In the 6-week vehicle-controlled trial, these adverse events included pyrexia (32% vs. 13% vehicle), URI (24% vs. 14%), nasopharyngitis (15% vs. 8%), gastroenteritis (7% vs. 3%), otitis media (4% vs. 0%), and diarrhea (8% vs. 0%). In the open-label phase of the trial, for infants who switched to Pimecrolimus Cream, 1% from vehicle, the incidence of the above-cited adverse events approached or equaled the incidence of those subjects who remained on Pimecrolimus Cream, 1%. In the 6-month safety data, 16% of Pimecrolimus and 35% of vehicle subjects discontinued early and 1.5% of Pimecrolimus and 0% of vehicle subjects discontinued due to adverse events. Infants on Pimecrolimus Cream, 1% had a greater incidence of some adverse events as compared to vehicle. These included pyrexia (30% vs. 20%), URI (21% vs. 17%), cough (15% vs. 9%), hypersensitivity (8% vs. 2%), teething (27% vs. 22%), vomiting (9% vs. 4%), rhinitis (13% vs. 9%), viral rash (4% vs. 0%), rhinorrhea (4% vs. 0%), and wheezing (4% vs. 0%). The systemic exposure to pimecrolimus from Pimecrolimus Cream, 1% was investigated in 28 pediatric subjects with atopic dermatitis (20%-80% BSA involvement) between the ages of 8 months-14 years. Following twice daily application for 3 weeks, blood concentrations of pimecrolimus were <2 ng/mL with 60% (96/161) of the blood samples having blood concentration below the limit of quantification (0.5 ng/mL). However, more children (23 children out of the total 28 children investigated) had at least one detectable blood level as compared to the adults (12 adults out of the total 52 adults investigated) over a 3-week treatment period. Due to the erratic nature of the blood levels observed, no correlation could be made between amount of cream, degree of BSA involvement, and blood concentrations. In general, the blood concentrations measured in adult atopic dermatitis subjects were comparable to those seen in the pediatric population. In a second group of 30 pediatric subjects aged 3-23 months with 10%-92% BSA involvement, following twice daily application for 3 weeks, blood concentrations of pimecrolimus were <2.6 ng/mL with 65% (75/116) of the blood samples having blood concentration below 0.5 ng/mL, and 27% (31/116) below the limit of quantification (0.1 ng/mL) for these trials. Overall, a higher proportion of detectable blood levels was seen in the pediatric subject population as compared to adult population. This increase in the absolute number of positive blood levels may be due to the larger surface area to body mass ratio seen in these younger subjects. In addition, a higher incidence of upper respiratory symptoms/infections was also seen relative to the older age group in the PK trials. At this time, a causal relationship between these findings and Pimecrolimus use cannot be ruled out. Nine (9) subjects ≥65 years old received Pimecrolimus Cream, 1% in Phase 3 trials. Clinical trials of Pimecrolimus Cream, 1% did not include sufficient numbers of subjects aged 65 and over to assess efficacy and safety.

Product summary:

Pimecrolimus Cream, 1% is a whitish cream NDC: 72162-1889-3: 30 g Creams in a TUBE Store at 25°C (77°F); excursions permitted to 15° to 30°C (59° to 86°F) [see USP Controlled Room Temperature]. Do not freeze. Repackaged/Relabeled by: Bryant Ranch Prepack, Inc. Burbank, CA 91504

Authorization status:

New Drug Application Authorized Generic

Patient Information leaflet

Bryant Ranch Prepack
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MEDICATION GUIDE
Pimecrolimus Cream, 1%
Important: Pimecrolimus Cream, 1% is for use on the skin only
(topical). Do not get Pimecrolimus
Cream, 1% in your eyes, nose, mouth, vagina, or rectum.
What is the most important information I should know about
Pimecrolimus Cream, 1%?
It is not known if Pimecrolimus Cream, 1% is safe to use for a long
period of time. A very small number
of people who have used Pimecrolimus Cream, 1% have developed cancer
(for example, skin cancer or
lymphoma). But a link that Pimecrolimus Cream, 1% use caused these
cancers has not been shown.
Because of this concern:
•
Do not use Pimecrolimus Cream, 1% continuously for a long time.
•
Use Pimecrolimus Cream, 1% only on areas of your skin that have
eczema.
•
Do not use Pimecrolimus Cream, 1% on a child under 2 years of age.
What is Pimecrolimus Cream, 1%?
Pimecrolimus Cream, 1% is a prescription medicine used on the skin
(topical) to treat mild to moderate
eczema (atopic dermatitis). Pimecrolimus Cream, 1% is for adults and
children age 2 years and older who
do not have a weakened immune system. Pimecrolimus Cream, 1% is used
on the skin for short periods,
and if needed, treatment may be repeated with breaks in between.
Pimecrolimus Cream, 1% 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.
It is not known if Pimecrolimus Cream, 1% is safe and effective in
people who have a weakened immune
system.
Pimecrolimus Cream, 1% is not for use in children under 2 years of
age.
Who should not use Pimecrolimus Cream, 1%?
Do not use Pimecrolimus Cream, 1% if you are allergic to pimecrolimus
or any of the ingredients in
Pimecrolimus Cream, 1%. See the end of this Medication Guide for a
complete list of ingredients in
Pimecrolimus Cream, 1%.
What should I tell my doctor before using Pimecrolimus Cream, 1%?
Before using Pimecrolimus Cream, 1%, tell your doctor about all of
your medical conditions, including if
you:
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Summary of Product characteristics

PIMECROLIMUS- PIMECROLIMUS CREAM
BRYANT RANCH PREPACK
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HIGHLIGHTS OF PRESCRIBING INFORMATION
THESE HIGHLIGHTS DO NOT INCLUDE ALL THE INFORMATION NEEDED TO USE
PIMECROLIMUS SAFELY
AND EFFECTIVELY. SEE FULL PRESCRIBING INFORMATION FOR PIMECROLIMUS.
PIMECROLIMUS CREAM, FOR TOPICAL USE
INITIAL U.S. APPROVAL: 2001
WARNING: LONG-TERM SAFETY OF TOPICAL CALCINEURIN INHIBITORS HAS NOT
BEEN
ESTABLISHED
_SEE FULL PRESCRIBING INFORMATION FOR COMPLETE BOXED WARNING._
ALTHOUGH 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 PIMECROLIMUS CREAM, 1%. (5.1)
THEREFORE:
•
•
INDICATIONS AND USAGE
Pimecrolimus Cream, 1% is a calcineurin inhibitor immunosuppressant
indicated as second-line therapy
for the short-term and non-continuous chronic treatment of mild to
moderate atopic dermatitis in non-
immunocompromised adults and children 2 years of age and older, who
have failed to respond adequately
to other topical prescription treatments, or when those treatments are
not advisable. (1)
DOSAGE AND ADMINISTRATION
•
•
•
•
DOSAGE FORMS AND STRENGTHS
Cream, 1%. (3)
CONTRAINDICATIONS
Pimecrolimus Cream, 1% is contraindicated in individuals with a
history of hypersensitivity to pimecrolimus
or any of the components of the cream. (4, 6.2)
WARNINGS AND PRECAUTIONS
•
•
•
ADVERSE REACTIONS
The most commonly reported adverse reactions (≥1%) were application
site burning, headache,
nasopharyngitis, cough, influenza, pyrexia and viral infection. (6.1)
TO REPORT SUSPECTED ADVERSE REACTIONS, CONTACT OCEANSIDE
PHARMACEUTICALS AT 1-800-
321-4576 OR FDA AT 1-800-FDA-1088 OR WWW.FDA.GOV/MEDWATCH.
SEE 17 FOR PATIENT COUNSELING INFORMATION AND MEDICATION GUIDE.
REVISED: 3/2024
CONTINUOUS LONG-TERM USE OF TOPICAL CALCINEURIN INHIBITORS, INCLUDING
PIMECROLIMUS
CREAM, 1%, IN ANY AGE GROUP SHOULD BE AVOIDED AND APPLICATION LIMITED
TO AREAS
OF INVOLVEMENT WITH ATOPIC DERMATITIS. (2, 5.1)
PIMECROLIM