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Guide
Drug Safety-related Labeling Changes (SrLC) Database
| ANDA | Abbreviated New Drug Application |
| BLA | Biologics License Application |
| CDER | Center for Drug Evaluation and Research |
| MG | Medication Guide |
| NDA | New Drug Application |
| PCI | Patient Counseling Information |
| PI | Patient Information |
| PLR | Physician Labeling Rule |
| PLLR | Pregnancy and Lactation Labeling Rule |
| Italics | For the most part, italics indicate an FDA comment such as:
Additions and/or revisions underlined These italics usually appear at the beginning of the section. In some cases, italics may be an inherent part of the label, and will most often appear in the body of the section. |
| Underlines | Any text that is underlined indicates text that has been added or revised. There are exceptions where underlining occurs in a section subtitle or heading. This is the case when there is just one word underlined in the body of the text. |
Sections
| BW | Box Warning |
| WP | Warnings and Precautions all in one section (PLR-format) Warnings as one section (pre-PLR format) Precautions as one section (pre-PLR format) |
| AR | Adverse Reactions (in pre-PLR format, this may be a subheading under precautions). |
| DI | Drug Interactions (in pre-PLR format, this may be a subheading under precautions). |
| USP | Use in Specific Populations (Inclusive on one or more of the following: Pregnancy; Lactation (PLLR- format); Nursing Mothers (pre-PLLR format); Females and Males of Reproductive Potential (PLLR format only); Pediatric Use, Geriatric Use, Renal Impairment, Hepatic Impairment, Sex, Race (these last six may be a subheading of precautions if label in pre-PLLR format. |
| PCI/PI/MG | Patient Counseling Information (PLR format only) - summarizes the information that a health care provider should convey to a patient (or caregiver when applicable) when a counseling discussion is taking place (e.g., a physician prescribing a drug during an office visit, a nurse providing discharge instructions at a hospital, or a pharmacist conveying information at a pharmacy). Patient Information - FDA approved patient labeling. Medication Guide - paper handouts that come with many prescription medicines. The guides address issues that are specific to particular drugs and drug classes, and they contain FDA-approved information that can help patients avoid serious adverse events. |
Only NDAs and CDER regulated BLAs are included in this database. ANDAs are not included.
Applications that remain active, even if the product has been discontinued, undergo safety-related labeling changes.
ARNUITY ELLIPTA (NDA-205625)
(FLUTICASONE FUROATE)
Safety-related Labeling Changes Approved by FDA Center for Drug Evaluation and Research (CDER)
10/18/2023 (SUPPL-11)
5 Warnings and Precautions
5.8 Hypersensitivity Reactions, including AnaphylaxisAdditions and revisions underlined:
Hypersensitivity reactions such as anaphylaxis, angioedema, urticaria, flushing, allergic dermatitis, and bronchospasm may occur after administration of ARNUITY ELLIPTA.
6 Adverse Reactions
6.2 Postmarketing ExperienceNewly added subsection:
In addition to adverse reactions reported from clinical trials, the following adverse reactions have been identified during postapproval use of ARNUITY ELLIPTA. 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. These events have been chosen for inclusion due to either their seriousness, frequency of reporting, or causal connection to ARNUITY ELLIPTA or a combination of these factors
Immune System Disorders
Hypersensitivity reactions including anaphylaxis, angioedema, rash, and urticaria.
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
PATIENT COUNSELING INFORMATIONAdditions and revisions underlined:
Advise patients that hypersensitivity reactions (e.g., anaphylaxis, angioedema, urticaria, flushing, allergic dermatitis, bronchospasm) may occur after administration of ARNUITY ELLIPTA.
03/01/2023 (SUPPL-9)
5 Warnings and Precautions
5.1 Oropharyngeal CandidiasisSubsection title revised
Additions and revisions underlined:
ARNUITY ELLIPTA contains fluticasone furoate, an ICS. Localized infections of the mouth and pharynx with Candida albicans have occurred in subjects treated with orally inhaled drug products containing fluticasone furoate. When such an infection develops, it should be treated with appropriate local or systemic (i.e., oral) antifungal therapy while treatment with ARNUITY ELLIPTA continues. In some cases, therapy with ARNUITY ELLIPTA may need to be interrupted. Advise the patient to rinse his/her mouth with water without swallowing following administration of ARNUITY ELLIPTA to help reduce the risk of oropharyngeal candidiasis.
Additions and revisions underlined:
Orally inhaled corticosteroids, including ARNUITY ELLIPTA, may cause a reduction in growth velocity when administered to pediatric patients. The safety and effectiveness of ARNUITY ELLIPTA have not been established in pediatric patients less than 5 years of age. Monitor the growth of pediatric patients receiving ARNUITY ELLIPTA routinely (e.g., via stadiometry). To minimize the systemic effects of orally inhaled corticosteroids, including ARNUITY ELLIPTA, titrate each patient’s dose to the lowest dosage that effectively controls his/her symptoms [see Dosage and Administration (2.2), Use in Specific Populations (8.4)].
Subsection title revised
Additions and revisions underlined:
Persons who are using drugs that suppress the immune system, such as corticosteroids, including ARNUITY ELLIPTA, are more susceptible to infections than healthy individuals. Chickenpox and measles can have a more serious or even fatal course in susceptible children or adults using corticosteroids. In such children or adults who have not had these diseases or been properly immunized, particular care should be taken to avoid exposure. How the dose, route, and duration of corticosteroid administration affect the risk of developing a disseminated infection is not known. The safety and effectiveness of ARNUITY ELLIPTA have not been established in pediatric patients less than 5 years of age and ARNUITY ELLIPTA is not indicated for use in this population. The contribution of the underlying disease and/or prior corticosteroid treatment to the risk is also not known. If a patient is exposed to chickenpox, prophylaxis with varicella zoster immune globulin (VZIG) or pooled intravenous immunoglobulin (IVIG) may be indicated. If a patient is exposed to measles, prophylaxis with pooled intramuscular immunoglobulin (IG) may be indicated. (See the Prescribing Information for VZIG, IVIG, and IG.) If chickenpox develops, treatment with antiviral agents may be considered.
ICS should be used with caution, if at all, in patients with active or quiescent tuberculosis infections of the respiratory tract; systemic fungal, bacterial, viral, or parasitic infections; or ocular herpes simplex.
6 Adverse Reactions
Additions and revisions underlined:
Systemic and local corticosteroid use may result in the following:
Oropharyngeal Candidiasis [see Warnings and Precautions (5.1)]
Immunosuppression and Risk of Infections [see Warnings and Precautions (5.3)]
Hypercorticism and Adrenal Suppression [see Warnings and Precautions (5.5)]
Reduction in BMD [see Warnings and Precautions (5.9)]
Growth Effects in Pediatrics [see Warnings and Precautions (5.10)]
Glaucoma and Cataracts [see Warnings and Precautions (5.11)]
8 Use in Specific Populations
8.4 Pediatric UseAdditions and revisions underlined:
The safety and effectiveness of ARNUITY ELLIPTA for maintenance treatment of asthma have been established in pediatric patients aged 5 years and older. Use of ARNUITY ELLIPTA for this indication in patients 12 years of age and older is supported by evidence from 4 adequate and well-controlled trials in adult and pediatric patients 12 years of age and older. Use of ARNUITY ELLIPTA for this indication in patients 5 to 11 years of age is supported by evidence from an adequate and well-controlled trial in patients 5 to 11 years of age [see Dosage and Administration (2.2), Adverse Reactions (6.1), and Clinical Studies (14.2)].
The safety and effectiveness of ARNUITY ELLIPTA have not been established in pediatric patients less than 5 years of age.
Effects on Growth
Orally inhaled corticosteroids may cause a reduction in growth velocity when administered to pediatric patients. A reduction of growth velocity in these patients may occur as a result of poorly controlled asthma or from use of corticosteroids, including ICS. The effects of long-term treatment of pediatric patients with ICS, including fluticasone furoate, on final adult height are not known.
. . .
A randomized, double blind, parallel-group, multicenter, 1-year, placebo-controlled trial evaluated the effect of once-daily treatment with ARNUITY ELLIPTA 50 mcg on growth velocity assessed by stadiometry. The subjects were 457 prepubertal children (girls aged 5 to younger than 8 years and boys aged 5 to younger than 9 years). Mean growth velocity over the 52-week treatment period was lower in the subjects receiving ARNUITY ELLIPTA (5.90 cm/year) compared with placebo (6.06 cm/year). The mean difference in growth velocity was - 0.16 cm/year (95% CI: -0.46, 0.14) [see Warnings and Precautions (5.10)].17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
Patient Counseling InformationAdditions and revisions underlined:
If they miss a dose, instruct patients to take it as soon as they remember, not to exceed 1 inhalation per day. Advise patients to take their next dose at the same time they normally do and to not take 2 doses at 1 time.
. . .
There have been reports of anaphylactic reactions in patients with severe milk protein allergy after inhalation of other powder medications containing lactose; therefore, patients with severe milk protein allergy should not use ARNUITY ELLIPTA. [See Warnings and Precautions (5.8).]
Additions and revisions underlined:
What is ARNUITY ELLIPTA?
ARNUITY ELLIPTA is an inhaled corticosteroid (ICS) medicine (fluticasone furoate).
ICS medicines such as fluticasone furoate help to decrease inflammation in the lungs. Inflammation in the lungs can lead to breathing problems.
ARNUITY ELLIPTA is not used to relieve sudden breathing problems and will not replace a rescue inhaler.
ARNUITY ELLIPTA is a prescription medicine used to prevent and control symptoms of asthma for better breathing.
01/07/2019 (SUPPL-7)
5 Warnings and Precautions
5.11 Glaucoma and Cataracts(additions underlined)
Glaucoma, increased intraocular pressure, and cataracts have been reported in patients with asthma following the long-term administration of ICS, including fluticasone furoate. Consider referral to an ophthalmologist in patients who develop ocular symptoms or ARNUITY ELLIPTA long term.
(additions underlined)
…
During periods of stress or a severe asthma attack, patients who have been withdrawn from systemic corticosteroids should be instructed to resume oral corticosteroids (in large doses) immediately and to contact their physicians for further instruction. These patients should also be instructed to carry a warning card indicating that they may need supplementary systemic corticosteroids during periods of stress or a severe asthma attack.
Patients requiring oral corticosteroids should be weaned slowly from systemic corticosteroid use after transferring to ARNUITY ELLIPTA. Prednisone reduction can be accomplished by reducing the daily prednisone dose by 2.5 mg on a weekly basis during therapy with ARNUITY ELLIPTA.
…
(additions underlined)
As with other inhaled medicines, ARNUITY ELLIPTA can produce paradoxical bronchospasm, which may be life threatening. If paradoxical bronchospasm occurs following dosing with ARNUITY ELLIPTA, it should be treated immediately with an inhaled, short-acting bronchodilator; ARNUITY ELLIPTA should be discontinued immediately; and alternative therapy should be instituted
(additions underlined)
Decreases in bone mineral density (BMD) have been observed with long-term administration of products containing ICS. The clinical significance of small changes in BMD with regard to long- term consequences such as fracture is unknown. Patients with major risk factors for decreased bone mineral content, such as prolonged immobilization, family history of osteoporosis, postmenopausal status, tobacco use, advanced age, poor nutrition, or chronic use of drugs that can reduce bone mass (e.g., anticonvulsants, oral corticosteroids) should be monitored and treated with established standards of care.
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
PATIENT COUNSELING INFORMATION(additions underlined)
…
Glaucoma and Cataracts
Advise patients that long-term use of ICS may increase the risk of some eye problems (cataracts or glaucoma); consider regular eye examinations.
...
(additions underlined)
…
Before using ARNUITY ELLIPTA, tell your healthcare provider about all of your medical conditions, including if you:
…
have eye problems such as glaucoma, increased pressure in your eye, cataracts, or other changes in vision.
…
Before using ARNUITY ELLIPTA, tell your healthcare provider about all of your medical conditions, including if you:
…
have eye problems such as glaucoma, increased pressure in your eye, cataracts, or other changes in vision.
05/17/2018 (SUPPL-5)
5 Warnings and Precautions
5.2 Acute Asthma Episodes(additions underlined)
ARNUITY ELLIPTA is not indicated for the relief of acute symptoms, i.e., as rescue therapy for treatment of acute episodes of bronchospasm. ARNUITY ELLIPTA has not been studied in the relief of acute symptoms and extra doses should not be used for that purpose. Acute symptoms should be treated with an inhaled, short-acting beta2-agonist. Instruct patients to contact their physicians immediately if episodes of asthma not responsive to bronchodilators occur during the course of treatment with ARNUITY ELLIPTA. During such episodes, patients may require therapy with oral corticosteroids.
6 Adverse Reactions
6.1 Clinical Trials Experience(additions underlined)
…
Adult and Adolescent Subjects Aged 12 Years and Older
The safety of ARNUITY ELLIPTA was evaluated in 10 double-blind, parallel-group, controlled trials (7 with placebo) of 8 to 76 weeks’ duration that enrolled 6,219 subjects with asthma. Doses of fluticasone furoate studied ranged from 25 to 800 mcg.
…
Pediatric Subjects Aged 5 to 11 Years
The safety data for pediatric subjects is based upon one 12-week clinical trial that enrolled 593 subjects with asthma aged 5 to 11 years. Dosages of fluticasone furoate studied were 25, 50, or 100 mcg administered once daily. ARNUITY ELLIPTA 50 mcg was studied in 120 subjects (46 females and 74 males). Adverse reactions (greater than or equal to 3% and greater than placebo) seen in pediatric subjects were similar to those reported in adult and adolescent subjects. Adverse reactions occurring in greater than or equal to 3% of subjects treated with ARNUITY ELLIPTA 50 mcg and greater than placebo were pharyngitis, bronchitis, and viral infection.
8 Use in Specific Populations
8.1 Pregnancy(PLLR conversion)
Risk Summary
There are insufficient data on the use of ARNUITY ELLIPTA in pregnant women. There are clinical considerations with use of ARNUITY ELLIPTA in pregnant women [see Clinical Considerations]. In animal reproduction studies, fluticasone furoate administered by inhalation to rats and rabbits during the period of organogenesis produced no fetal structural abnormalities. The highest fluticasone furoate doses in the rat and rabbit studies were 4 times and 1 times the maximum recommended human daily inhalation dose (MRHDID), respectively.The estimated risk of major birth defects and miscarriage for the indicated populations is unknown. In the U.S. general population, the estimated risk of major birth defects and miscarriage in clinically recognized pregnancies is 2% to 4% and 15% to 20%, respectively.
Clinical Considerations
Disease-Associated Maternal and/or Embryofetal Risk: In women with poorly or moderately controlled asthma, there is an increased risk of several perinatal adverse outcomes such as pre-eclampsia in the mother and prematurity, low birth weight, and small for gestational age in the neonate.
Pregnant women with asthma should be closely monitored and medication adjusted as necessary to maintain optimal asthma control.
Data
Animal Data: Fluticasone Furoate: In 2 separate embryofetal developmental studies, pregnant rats and rabbits received fluticasone furoate during the period of organogenesis at doses up to approximately 4 and 1 times the MRHDID, respectively (on a mcg/m2 basis at maternal inhalation doses up to 91 and 8 mcg/kg/day). No evidence of structural abnormalities in fetuses was observed in either species. In a perinatal and postnatal developmental study in rats, dams received fluticasone furoate during late gestation and lactation periods at doses up to approximately 1 time the MRHDID (on a mcg/m2 basis at maternal inhalation doses up to 27 mcg/kg/day). No evidence of effects on offspring development was observed.
(PLLR conversion)
Risk Summary
There is no information available on the presence of fluticasone furoate in human milk, the effects on the breastfed child, or the effects on milk production. Low concentrations of other inhaled corticosteroids have been detected in human milk. The developmental and health benefits of breastfeeding should be considered along with the mother’s clinical need for ARNUITY ELLIPTA and any potential adverse effects on the breastfed child from fluticasone furoate or from the underlying maternal condition.
(additions underlined)
The safety and efficacy of ARNUITY ELLIPTA in pediatric patients with asthma aged 5 to 11 years have been established in 3 clinical trials. In those trials, 234 subjects were administered ARNUITY ELLIPTA 50 mcg once daily. Subjects aged 5 to 11 years demonstrated safety and efficacy results similar to those observed in subjects aged 12 years and older. The safety and efficacy of ARNUITY ELLIPTA have not been established in pediatric patients aged younger than 5 years.
…
A randomized, double-blind, parallel-group, multicenter, 1-year, placebo-controlled trial evaluated the effect of once-daily treatment with 110 mcg of fluticasone furoate in the nasal spray formulation on growth velocity assessed by stadiometry. The systemic exposure of fluticasone furoate in this trial is lower than that of ARNUITY ELLIPTA 50 mcg. The subjects were 474 prepubescent children (girls aged 5 to 7.5 years and boys aged 5 to 8.5 years). Mean growth velocity over the 52-week treatment period was lower in the subjects receiving fluticasone furoate nasal spray (5.19 cm/year) compared with placebo (5.46 cm/year). The mean reduction in growth velocity was 0.27 cm/year (95% CI: 0.06, 0.48).
(additions underlined)
Fluticasone furoate systemic exposure increased by up to 3-fold in adult subjects with hepatic impairment compared with healthy subjects. Use ARNUITY ELLIPTA with caution in patients with moderate or severe hepatic impairment. Monitor patients for corticosteroid-related side effects. The effect of hepatic impairment on fluticasone furoate systemic exposure in subjects aged younger than 18 years has not been evaluated.
17 PCI/PI/MG (Patient Counseling Information/Patient Information/Medication Guide)
Patient Information(additions and revisions, please refer to label)