Home › NDC Lookup › Ingredients › Fluticasone Propionate And Salmeterol Xi... › 66993-0088-96
Fluticasone Propionate and Salmeterol HFA fluticasone propionate and salmeterol xinafoate 230 ug; 21 ug Aerosol, Metered — NDC 66993-0088-96 package photo
Label image from the product's FDA listing (DailyMed) — may show a different pack size or an older label revision.

Fluticasone Propionate and Salmeterol HFA fluticasone propionate and salmeterol xinafoate 230 ug; 21 ug Aerosol, Metered — NDC 66993-088-96 (Billing 66993-0088-96)

by Prasco Laboratories · 1 INHALER in 1 CARTON / 120 AEROSOL, METERED in 1 INHALER

This is a package of Fluticasone Propionate and Salmeterol HFA fluticasone propionate and salmeterol xinafoate 230 ug; 21 ug Aerosol, Metered from Prasco Laboratories, marketed since Mar 2023 and currently FDA-listed; retail pharmacies pay about $26.75 per g (NADAC). It is this product's only package size.

NDC 66993-0088-96
🏷️ FDA NDC (as labeled) 66993-088-96 billing pads the product segment with a zero
Rx only Brand On market Non-controlled ⇄ Compare with another NDC
🗂️ FDA directory synced Oct 8, 2026 · this listing last changed Oct 1, 2026 · sources: openFDA · FDA label (DailyMed) · FDA Orange & Purple Book · First Databank · CMS NADAC, ASP, Medicare & Medicaid · RxNorm
📋 All sources & update times →

This page is curated, coded, and maintained by

Compiled from public FDA, CMS, DailyMed, NADAC, and related drug data sources. Editorial policy

NDC database record

One package, one record: these facts belong to NDC 66993-088-96 alone.

Record
FDA NDC Directory package listing · Human prescription drug
Code segments
66993 labeler · 088 product · 96 package
Package marketed since
Mar 1, 2023
Sample package
No — commercial package
Listing certified through
Dec 31, 2027
Barcode (UPC-A, from the NDC)
3 6699308896 9
Medicaid fills, this package
18,558 prescriptions in the last four reported quarters
FDA record last changed
Oct 1, 2026

Identity & classification

Regulatory identifiers FDA, NLM and CMS codes for this package

FDA NDC (as labeled) 66993-088-96
Product NDC 66993-088
11-digit billing NDC 66993008896
NCPDP billing unit GM — per gram (weight)
RxCUI 896236, 896244, 896272
UNII O2GMZ0LF5W, 6EW8Q962A5
Application # NDA021254
SPL Set ID 666c5b12-a4f7-4c53-8261-4742b5e5a6df
Established class (EPC) Corticosteroid; beta2-Adrenergic Agonist
Mechanism of action Adrenergic beta2-Agonists; Corticosteroid Hormone Receptor Agonists
DEA schedule Non-controlled
Marketing category NDA AUTHORIZED GENERIC
Marketing status On market
FDA listing status Listed (active directory)
Marketing start 2023-03-01
Route RESPIRATORY (INHALATION)
Dosage form AEROSOL, METERED
Substance FLUTICASONE PROPIONATE; SALMETEROL XINAFOATE

Drug-database identifiers Medi-Span GPI and First Databank GCN / HICL / AHFS classification

GPI-14 44209902703270
GCN Seq No 061345
GCN 97137
HICL code 019963
Ingredient (HICL) Fluticasone Propion/Salmeterol
HIC1 code B
Therapeutic class — broad (HIC1) Respiratory System
HIC2 code B6
Therapeutic class — intermediate (HIC2) Drugs Affecting The Trachea And Bronchi (Cont3)
HIC3 code B63
Therapeutic class — specific (HIC3) Beta-Adrenergic And Glucocorticoid Combo, Inhaled
AHFS code 12:12.08.12
AHFS class Selective Beta-2-Adrenergic Agonists
FDB label name FLUTICASONE-SALMETEROL 230-21
FDB brand name Fluticasone-Salmeterol Hfa
Legend status F — Federal legend — prescription drug or device
Quick answers
  • GSN (GCN sequence number): 061345
  • GCN: 97137
  • GPI-14 (Medi-Span): 44209902703270
  • HICL (First Databank): 019963
  • AHFS class code: 12:12.08.12
  • RxCUI (RxNorm): 896236
Why two NDCs? The FDA registers this code as 66993-088-96 — a 5-3-2 layout, and that's what's printed on the package and shown on DailyMed. For insurance claims, every NDC is standardized to a uniform 11-digit 5-4-2 format by adding a zero to the product segment → 66993-0088-96. Same drug, same package — only the format differs.
Where does this data come from?
Identifiers from the FDA openFDA NDC Directory and Structured Product Labeling; RxCUI from RxNorm (NLM); GPI from Medi-Span; GCN / HIC / AHFS / legend from First Databank.

RxNorm drug class

This medicine belongs to the beta2-Adrenergic Agonist class.

Pharmacologic class beta2-Adrenergic Agonist
Drug family (ATC) Selective beta-2-adrenoreceptor agonists
How it works Adrenergic beta2-Agonists
Where does this data come from?
Therapeutic classes from RxNorm RxClass (U.S. National Library of Medicine) — Established Pharmacologic Class (FDA), ATC drug family (WHO) and mechanism of action, matched by this product’s RxCUI.

Clinical

Label name FLUTICASONE-SALMETEROL 230-21 Ingredient Fluticasone Propion/Salmeterol
📗 Our plain-language guide HelloPharmacist
  • It's a twice-daily controller for asthma in people 4 and older. The inhalation powder is also used for COPD maintenance. It's not for sudden attacks, so keep your rescue inhaler cl...
  • Take one inhalation twice a day, about 12 hours apart, and don't take extra. Rinse your mouth with water afterward and spit it out. That helps prevent a yeast infection in your mou...
  • Use your short-acting rescue inhaler, not extra doses of this one. If you need the rescue inhaler more and more, call your doctor, since that can mean your asthma is getting worse.
  • What if I feel short of breath between doses?
📖 Read our full Fluticasone and Salmeterol Oral Inhalation guide →

Supplement & herbal interactions

🌿 Drug–supplement interaction checker →
Where does this data come from?
Plain-language summary from MedlinePlus (U.S. National Library of Medicine); supplement & herbal interactions and nutrient depletion data from the Natural Medicines database; our full guide is HelloPharmacist editorial content.

Pricing

A drug doesn't have one price. Each row is a different public payment system, and none is what you'd pay at the counter — that depends on your insurance. The ⓘ on each row explains what it measures.

Price systemPer gPer package
Retail pharmacies payNADAC · weekly $26.746 —
Medicaid paysCMS SDUD · 12 mo $32.52 —
Medicare drug plans payPart D · Q2 2026 $38.02 —
NADAC price history (per g) — tap or hover for the price & month
Dec 2023 Feb 2026 May 2026 Sep 2026 $27.443 $26.714
▼ Down 1% over the last 11 months.
Where does this data come from?
NADAC (National Average Drug Acquisition Cost) is the CMS weekly pharmacy-acquisition-cost survey — what pharmacies pay. ASP (Average Sales Price) is the CMS Medicare Part B drug-payment file, published quarterly. Medicaid pays is computed by us from CMS State Drug Utilization Data (total reimbursed ÷ units, trailing 12 months) — gross of rebates and inclusive of dispensing fees, so it reflects what Medicaid paid, not an acquisition cost. Medicare drug plans pay is the median negotiated point-of-sale unit cost across plans listing this NDC in the CMS quarterly Prescription Drug Plan pricing files, before rebates. The VA pays is the federal contract price (FSS, and the statutory Big 4 ceiling where listed) from the VA National Acquisition Center pharmaceutical price file. All are free public government data; each measures a different payer, so the figures are not directly comparable.

Packaging — all sizes for this product

Package NDCDescription Marketing startMarketing endStatus
66993-0088-96 You're viewing this Main listing 1 INHALER in 1 CARTON / 120 AEROSOL, METERED in 1 INHALER 2023-03-01 — Active

Therapeutic equivalents

ProductLabelerPackNADAC/unitTEStatusPrice vs. this
Fluticasone Propionate and Salmeterol HFA 230 ug/1; 21 ugthis 66993-0088-96 Prasco 1 inhaler $26.746 — Availability likely —
Advair Hfa 230 ug/1; 21 ug 00173-0717-20 GlaxoSmithKline 1 inhaler $35.018 — Availability likely +31%
About this product: this is an authorized generic — the brand-name product marketed without its brand name. Other versions are listed above, least expensive first.
Where does this data come from?
Equivalents are other NDCs of the same ingredient, form and route from the openFDA NDC Directory, ranked least-expensive-first by NADAC. Therapeutic-equivalence (AB) ratings come from the FDA Orange Book; biologics use the FDA Purple Book for biosimilar & interchangeable status.

Availability & generic status

🏛️
2023
On the market since
Mar 2023
📍
2026
Currently FDA-listed
3 years listed
🔒
·
No generic listed yet
brand only
ℹ️No FDA-approved generic found

We did not find an FDA-approved generic match for this exact strength, form and route.

Where does this data come from?
Patents and exclusivity from the FDA Orange Book (small-molecule drugs), refreshed from public FDA data. Generic launch timing is an estimate, not a guarantee.

Inactive Ingredients / Excipients

Inactive ingredients, also called excipients, are components of the drug product other than the active ingredient. They may include fillers, dyes, coatings, preservatives, flavors, or other formulation ingredients.

🧪 Avoiding an ingredient? See Fluticasone and Salmeterol Oral Inhalation inactive ingredients by manufacturer: every current product's list side by side, so you can ask your pharmacy for the version that does not list it.

💡 Tap an ingredient (hover on desktop) to see what it is and why it’s used.

  • UNII DH9E53K1Y8
    A synthetic fluorinated hydrocarbon used primarily as a propellant or aerosol dispersant in pressurized inhaler formulations to help deliver medication to the lungs.

1 inactive ingredient listed in the exact product block matched to this NDC.

Where does this data come from?
Data sourced from official FDA Structured Product Labeling (SPL) via DailyMed — ingredient classCode="IACT" elements from the exact product block matched by this NDC. Label-section narrative from DailyMed / the openFDA label index is shown separately when available.

Inactive ingredient FAQ

Are inactive ingredients the same for every manufacturer?
No. Inactive ingredients can differ by manufacturer, dosage form, strength, and package / product version.
Why might an inactive ingredient be missing?
Some SPLs do not provide a complete structured inactive-ingredient list, and older or unusual labels may only include the information in narrative text.
Can inactive ingredients matter?
Yes. They can matter for allergies, intolerances, dyes, gluten / lactose concerns, preservatives, and formulation differences — but confirm with a pharmacist or the manufacturer when it’s clinically important.

Manufacturer & labeler

LabelerPrasco Laboratories
Application holderGLAXO GROUP LTD ENGLAND DBA GLAXOSMITHKLINE
FDA applicationNDA021254 (NDA AUTHORIZED GENERIC)
Labeler code66993
First marketedMar 2023
Product typeHuman Prescription Drug
Portfolio106 products on file

More NDCs from Prasco Laboratories labeler code 66993

The labeler markets the product; the application holder owns the FDA approval. They’re often the same company but can differ (e.g. a repackager or an authorized generic). A mailing address / phone appears here when the manufacturer includes it in the product’s FDA label (not all do).
Where does this data come from?
Labeler, application holder and registered establishment from the FDA openFDA NDC Directory and Drugs@FDA; address/contact from the product’s FDA label.

Full prescribing information FDA SPL

The complete FDA label for this product — the official prescribing information, verbatim, section by section. Very long sections are excerpted here and marked; the full text is on DailyMed (linked in the sources below). Jump with a chip, search within the label, or expand everything.
🎯 Indications and Usage ⏱️ Dosage and Administration 💊 Dosage Forms and Strengths ⛔ Contraindications ⚠️ Warnings and Cautions 🤒 Adverse Reactions 🔄 Drug Interactions 👥 Use in Specific Populations 🤰 Pregnancy 🧒 Pediatric Use 🧓 Geriatric Use 🆘 Overdosage 🧬 Clinical Pharmacology 🧬 Mechanism of Action 📦 How Supplied / Storage and Handling 📋 Description 💬 Information for Patients 🧬 Pharmacokinetics 🧬 Pharmacodynamics 🔬 Clinical Studies 🧪 Nonclinical Toxicology 📄 Carcinogenesis, Mutagenesis, Impairment of Fertility 📄 Patient Package Insert 📖 Instructions for Use 📄 Package Label / Principal Display Panel
🎯 Indications and Usage 139 words ▾

1 INDICATIONS AND USAGE Fluticasone Propionate and Salmeterol HFA is indicated for treatment of asthma in adult and adolescent patients aged 12 years and older. Fluticasone Propionate and Salmeterol HFA should be used for patients not adequately controlled on a long-term asthma control medication such as an inhaled corticosteroid (ICS) or whose disease warrants initiation of treatment with both an ICS and long-acting beta 2 -adrenergic agonist (LABA). Limitations of Use Fluticasone Propionate and Salmeterol HFA is not indicated for the relief of acute bronchospasm.

Fluticasone Propionate and Salmeterol HFA is a combination of fluticasone propionate, an inhaled corticosteroid, and salmeterol, a long-acting beta 2 ‑adrenergic agonist (LABA), indicated for treatment of asthma in adult and adolescent patients aged 12 years and older. ( 1 ) Limitations of use: Not indicated for relief of acute bronchospasm. ( 1 )

⏱️ Dosage and Administration ~2 min read ▾

2 DOSAGE AND ADMINISTRATION • For oral inhalation only. ( 2.1 ) • Adult and adolescent patients aged 12 years and older: 2 inhalations of Fluticasone Propionate and Salmeterol HFA 45 mcg/21 mcg, Fluticasone Propionate and Salmeterol HFA 115 mcg/21 mcg, or Fluticasone Propionate and Salmeterol HFA 230 mcg/21 mcg twice daily. ( 2.2 ) • Starting dosage is based on asthma severity. ( 2.2 )

2.1Administration Information Fluticasone Propionate and Salmeterol HFA should be administered by the orally inhaled route only. After inhalation, rinse mouth with water without swallowing to help reduce the risk of oropharyngeal candidiasis. Priming Prime Fluticasone Propionate and Salmeterol HFA before using for the first time by releasing 4 sprays into the air away from the face, shaking well for 5 seconds before each spray.

In cases where the inhaler has not been used for more than 4 weeks or when it has been dropped, prime the inhaler again by releasing 2 sprays into the air away from the face, shaking well for 5 seconds before each spray. Avoid spraying in eyes.

2.2Recommended Dosage Adult and adolescent patients aged 12 years and older: 2 oral inhalations twice daily, approximately 12 hours apart. The maximum recommended dosage is 2 inhalations of Fluticasone Propionate and Salmeterol HFA 230 mcg/21 mcg twice daily. General Dosing Recommendation When choosing the starting dosage strength of Fluticasone Propionate and Salmeterol HFA, consider the patients’ disease severity, based on their previous asthma therapy, including the ICS dosage, as well as the patients’ current control of asthma symptoms and risk of future exacerbation.

If asthma symptoms arise in the period between doses, an inhaled, short-acting beta 2 -agonist should be used for immediate relief. Improvement in asthma control following inhaled administration of Fluticasone Propionate and Salmeterol HFA can occur within 30 minutes of beginning treatment, although maximum benefit may not be achieved for 1 week or longer after starting treatment. Individual patients will experience a variable time to onset and degree of symptom relief.

For patients who do not respond adequately to the starting dosage after 2 weeks of therapy, replacing the current strength of Fluticasone Propionate and Salmeterol HFA with a higher strength may provide additional improvement in asthma control. If a previously effective dosage regimen fails to provide adequate improvement in asthma control, the therapeutic regimen should be reevaluated and additional therapeutic options (e.g., replacing the current strength of Fluticasone Propionate and Salmeterol HFA with a higher strength, adding additional ICS, initiating oral corticosteroids) should be considered.

More frequent administration or a greater number of inhalations (more than 2 inhalations twice daily) of the prescribed strength of Fluticasone Propionate and Salmeterol HFA is not recommended as some patients are more likely to experience adverse effects with higher doses of salmeterol. Patients using Fluticasone Propionate and Salmeterol HFA should not use additional LABA for any reason. [See Warnings and Precautions ( 5.3 , 5.12 ).]

💊 Dosage Forms and Strengths 98 words ▾

3 DOSAGE FORMS AND STRENGTHS Inhalation aerosol: purple plastic inhaler with a light purple cap containing a pressurized metered-dose aerosol canister containing 120 metered inhalations and fitted with a counter. • 45 mcg fluticasone propionate/21 mcg salmeterol from the mouthpiece per actuation • 115 mcg fluticasone propionate/21 mcg salmeterol from the mouthpiece per actuation • 230 mcg fluticasone propionate/21 mcg salmeterol from the mouthpiece per actuation Inhalation aerosol: • 45 mcg fluticasone propionate/21 mcg salmeterol per actuation (3) • 115 mcg fluticasone propionate/21 mcg salmeterol per actuation (3) • 230 mcg fluticasone propionate/21 mcg salmeterol per actuation (3)

⛔ Contraindications 85 words ▾

4 CONTRAINDICATIONS Fluticasone Propionate and Salmeterol HFA is contraindicated in the following conditions: • Primary treatment of status asthmaticus or other acute episodes of asthma where intensive measures are required [see Warnings and Precautions ( 5.2 )] . • Hypersensitivity to any of the ingredients [see Warnings and Precautions ( 5.11 ), Adverse Reactions ( 6.2 ), Description ( 11 )] . • Primary treatment of status asthmaticus or acute episodes of asthma requiring intensive measures. ( 4 ) • Hypersensitivity to any ingredient.

(4)

⚠️ Warnings and Cautions ~3 min read ▾

5 WARNINGS AND PRECAUTIONS • LABA monotherapy increases the risk of serious asthma-related events. (5.1) • Do not initiate in acutely deteriorating asthma or to treat acute symptoms. (5.2) • Do not use in combination with an additional medicine containing a LABA because of risk of overdose.

(5.3) • Candida albicans infection of the mouth and pharynx may occur. Monitor patients periodically. Advise the patient to rinse his/her mouth with water without swallowing after inhalation to help reduce the risk.

( 5.4 ) • Increased risk of pneumonia in patients with COPD. Monitor patients for signs and symptoms of pneumonia. ( 5.5 ) • Potential worsening of infections (e.g., existing tuberculosis; fungal, bacterial, viral, or parasitic infections; ocular herpes simplex).

Use with caution in patients with these infections. More serious or even fatal course of chickenpox or measles can occur in susceptible patients. ( 5.6 ) • Risk of impaired adrenal function when transferring from systemic corticosteroids.

Taper patients slowly from systemic corticosteroids if transferring to Fluticasone Propionate and Salmeterol HFA. ( 5.7 ) • Hypercorticism and adrenal suppression may occur with very high dosages or at the regular dosage in susceptible individuals. If such changes occur, discontinue Fluticasone Propionate and Salmeterol HFA slowly.

( 5.8 ) • If paradoxical bronchospasm occurs, discontinue Fluticasone Propionate and Salmeterol HFA and institute alternative therapy. ( 5.10 ) • Use with caution in patients with cardiovascular or central nervous system disorders because of beta-adrenergic stimulation. ( 5.12 ) • Assess for decrease in bone mineral density initially and periodically thereafter.

( 5.13 ) • Monitor growth of pediatric patients. ( 5.14 ) • Glaucoma and cataracts may occur with long-term use of inhaled corticosteroids. Consider referral to an ophthalmologist in patients who develop ocular symptoms or use Fluticasone Propionate and Salmeterol HFA long term.

( 5.15 ) • Be alert to eosinophilic conditions, hypokalemia, and hyperglycemia. ( 5.16 , 5.18 ) • Use with caution in patients with convulsive disorders, thyrotoxicosis, diabetes mellitus, and ketoacidosis. ( 5.17 )

5.1Serious Asthma-Related Events – Hospitalizations, Intubations, Death Use of LABA as monotherapy (without ICS) for asthma is associated with an increased risk of asthma-related death [see Salmeterol Multicenter Asthma Research Trial (SMART)] . Available data from controlled clinical trials also suggest that use of LABA as monotherapy increases the risk of asthma-related hospitalization in pediatric and adolescent patients. These findings are considered a class effect of LABA monotherapy.

When LABA are used in fixed-dose combination with ICS, data from large clinical trials do not show a significant increase in the risk of serious asthma-related events (hospitalizations, intubations, death) compared with ICS alone (see Serious Asthma-Related Events with Inhaled Corticosteroid/Long-acting Beta 2 -adrenergic Agonists) . Serious Asthma-Related Events with Inhaled Corticosteroid/Long-acting Beta 2 -adrenergic Agonists Four (4) large, 26-week, randomized, double-blind, active-controlled clinical safety trials were conducted to evaluate the risk of serious asthma-related events when LABA were used in fixed‑dose combination with ICS compared with ICS alone in subjects with asthma.

Three (3) trials included adult and adolescent subjects aged 12 years and older: 1 trial compared fluticasone propionate/salmeterol inhalation powder with fluticasone propionate inhalation powder, 1 trial compared mometasone furoate/formoterol with mometasone furoate, and 1 trial compared budesonide/formoterol with budesonide. The fourth trial included pediatric subjects aged 4 to 11 years and compared fluticasone propionate/salmeterol inhalation powder with fluticasone propionate inhalation powder. The primary safety endpoint for all 4 trials was serious asthma-related events (hospitalizatio… [Excerpted — this section continues on DailyMed.]

🤒 Adverse Reactions ~3 min read ▾

6 ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the labeling: • Serious asthma-related events – hospitalizations, intubations, death [see Warnings and Precautions ( 5.1 )] • Oropharyngeal candidiasis [see Warnings and Precautions ( 5.4 )] • Pneumonia in patients with COPD [see Warnings and Precautions ( 5.5 )] • Immunosuppression and risk of infections [see Warnings and Precautions ( 5.6 )] • Hypercorticism and adrenal suppression [see Warnings and Precautions ( 5.8 )] • Cardiovascular and central nervous system effects [see Warnings and Precautions ( 5.12 )] • Reduction in bone mineral density [see Warnings and Precautions ( 5.13 )] • Growth effects [see Warnings and Precautions ( 5.14 )] • Glaucoma and cataracts [see Warnings and Precautions ( 5.15 )] Most common adverse reactions (incidence ≥3%) include: upper respiratory tract infection or inflammation, throat irritation, dysphonia, headache, dizziness, nausea and vomiting.

( 6.1 ) To report SUSPECTED ADVERSE REACTIONS, contact Prasco Laboratories at 1-866-525-0688 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch .

6.1Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in practice. Adult and Adolescent Subjects Aged 12 Years and Older The incidence of adverse reactions associated with fluticasone propionate and salmeterol HFA in Table 2 is based upon two 12-week, placebo-controlled, U.S. clinical trials (Trials 1 and 3) and 1 active-controlled 12-week U.S. clinical trial (Trial 2).

A total of 1,008 adult and adolescent subjects with asthma (556 females and 452 males) previously treated with albuterol alone, salmeterol, or ICS were treated twice daily with 2 inhalations of fluticasone propionate and salmeterol HFA 45 mcg/21 mcg or fluticasone propionate and salmeterol HFA 115 mcg/21 mcg, fluticasone propionate CFC inhalation aerosol (44- or 110-mcg doses), salmeterol CFC inhalation aerosol 21 mcg, or placebo HFA inhalation aerosol. The average duration of exposure was 71 to 81 days in the active treatment groups compared with 51 days in the placebo group.

Table 2. Adverse Reactions with Fluticasone Propionate and Salmeterol HFA with ≥3% Incidence in Adult and Adolescent Subjects with Asthma Adverse Event Fluticasone Propionate and Salmeterol HFA Fluticasone Propionate CFC Inhalation Aerosol Salmeterol CFC Inhalation Aerosol Placebo HFA Inhalation Aerosol 45 mcg/21 mcg (n = 187) % 115 mcg/21 mcg (n = 94) % 44 mcg (n = 186) % 110 mcg (n = 91) % 21 mcg (n = 274) % (n = 176) % Ear, nose, and throat Upper respiratory tract infection 16 24 13 15 17 13 Throat irritation 9 7 12 13 9 7 Upper respiratory inflammation 4 4 3 7 5 3 Hoarseness/dysphonia 3 1 2 0 1 0 Lower respiratory Viral respiratory infection 3 5 4 5 3 4 Neurology Headache 21 15 24 16 20 11 Dizziness 4 1 1 0 <1 0 Gastrointestinal Nausea and vomiting 5 3 4 2 2 3 Viral gastrointestinal infection 4 2 2 0 1 2 Gastrointestinal signs and symptoms 3 2 2 1 1 1 Musculoskeletal Musculoskeletal pain 5 7 8 2 4 4 Muscle pain 4 1 1 1 3 <1 The incidence of common adverse reactions reported in Trial 4, a 12-week non-U.S. clinical trial in 509 subjects previously treated with ICS who were treated twice daily with 2 inhalations of fluticasone propionate and salmeterol HFA 230 mcg/21 mcg, fluticasone propionate CFC inhalation aerosol 220 mcg, or 1 inhalation of ADVAIR DISKUS 500 mcg/50 mcg was similar to the incidences reported in Table 2.

Additional Adverse Reactions Other adverse reactions not previously listed, whether considered drug-related or not by the investigators, that occurred in the groups receiving fluticasone propionate and salmeterol HFA with an incidence of 1% to 3% and that occurred at a greater incidence than with placebo include the following… [Excerpted — this section continues on DailyMed.]

🔄 Drug Interactions ~2 min read ▾

7 DRUG INTERACTIONS Fluticasone propionate and salmeterol HFA has been used concomitantly with other drugs, including short-acting beta 2 -agonists, methylxanthines, and nasal corticosteroids, commonly used in patients with asthma without adverse drug reactions [see Clinical Pharmacology ( 12.2 )] . No formal drug interaction trials have been performed with fluticasone propionate and salmeterol HFA. • Strong cytochrome P450 3A4 inhibitors (e.g., ritonavir, ketoconazole): Use not recommended. May increase risk of systemic corticosteroid and cardiovascular effects.

( 7.1 ) • Monoamine oxidase inhibitors and tricyclic antidepressants: Use with extreme caution. May potentiate effect of salmeterol on vascular system. ( 7.2 ) • Beta-blockers: Use with caution.

May block bronchodilatory effects of beta-agonists and produce severe bronchospasm. ( 7.3 ) • Diuretics: Use with caution. Electrocardiographic changes and/or hypokalemia associated with non–potassium-sparing diuretics may worsen with concomitant beta-agonists.

( 7.4 )

7.1Inhibitors of Cytochrome P450 3A4 Fluticasone propionate and salmeterol, the individual components of Fluticasone Propionate and Salmeterol HFA, are substrates of CYP3A4. The use of strong CYP3A4 inhibitors (e.g., ritonavir, atazanavir, clarithromycin, indinavir, itraconazole, nefazodone, nelfinavir, saquinavir, ketoconazole, telithromycin) with Fluticasone Propionate and Salmeterol HFA is not recommended because increased systemic corticosteroid and increased cardiovascular adverse effects may occur. Ritonavir Fluticasone Propionate: A drug interaction trial with fluticasone propionate aqueous nasal spray in healthy subjects has shown that ritonavir (a strong CYP3A4 inhibitor) can significantly increase plasma fluticasone propionate exposure, resulting in significantly reduced serum cortisol concentrations [see Clinical Pharmacology ( 12.3 )] .

During postmarketing use, there have been reports of clinically significant drug interactions in patients receiving fluticasone propionate and ritonavir, resulting in systemic corticosteroid effects including Cushing’s syndrome and adrenal suppression. Ketoconazole Fluticasone Propionate: Coadministration of orally inhaled fluticasone propionate (1,000 mcg) and ketoconazole (200 mg once daily) resulted in a 1.9-fold increase in plasma fluticasone propionate exposure and a 45% decrease in plasma cortisol area under the curve (AUC), but had no effect on urinary excretion of cortisol.

Salmeterol: In a drug interaction trial in 20 healthy subjects, coadministration of inhaled salmeterol (50 mcg twice daily) and oral ketoconazole (400 mg once daily) for 7 days resulted in greater systemic exposure to salmeterol (AUC increased 16-fold and C max increased 1.4-fold). Three (3) subjects were withdrawn due to beta 2 -agonist side effects (2 with prolonged QTc and 1 with palpitations and sinus tachycardia). Although there was no statistical effect on the mean QTc, coadministration of salmeterol and ketoconazole was associated with more frequent increases in QTc duration compared with salmeterol and placebo administration.

7.2Monoamine Oxidase Inhibitors and Tricyclic Antidepressants Fluticasone Propionate and Salmeterol HFA should be administered with extreme caution to patients being treated with monoamine oxidase inhibitors or tricyclic antidepressants, or within 2 weeks of discontinuation of such agents, because the action of salmeterol, a component of Fluticasone Propionate and Salmeterol HFA, on the vascular system may be potentiated by these agents.

7.3Beta-adrenergic Receptor Blocking Agents Beta-blockers not only block the pulmonary effect of beta-agonists, such as salmeterol, a component of Fluticasone Propionate and Salmeterol HFA, but may also produce severe bronchospasm in patients with asthma. Therefore, patients with asthma should not normally be treated with beta-blockers. However, under certain circumstances, there may be no acceptable alternatives to the use… [Excerpted — this section continues on DailyMed.]

👥 Use in Specific Populations ~3 min read ▾

8 USE IN SPECIFIC POPULATIONS Hepatic impairment: Monitor patients for signs of increased drug exposure. (8.6)

8.1Pregnancy Risk Summary There are insufficient data on the use of fluticasone propionate and salmeterol HFA or individual monoproducts, fluticasone propionate and salmeterol xinafoate, in pregnant women. There are clinical considerations with the use of fluticasone propionate and salmeterol HFA in pregnant women. (See Clinical Considerations.) In animals, teratogenicity characteristic of corticosteroids, decreased fetal body weight and/or skeletal variations, in rats, mice, and rabbits, was observed with subcutaneously administered maternal toxic doses of fluticasone propionate less than the maximum recommended human daily inhaled dose (MRHDID) on a mcg/m 2 basis.

(See Data.) However, fluticasone propionate administered via inhalation to rats decreased fetal body weight but did not induce teratogenicity at a maternal toxic dose less than the MRHDID on a mcg/m 2 basis. (See Data.) Experience with oral corticosteroids suggests that rodents are more prone to teratogenic effects from corticosteroids than humans. Oral administration of salmeterol to pregnant rabbits caused teratogenicity characteristic of beta-adrenoceptor stimulation at maternal doses approximately 25 times the MRHDID on an AUC basis.

These adverse effects generally occurred at large multiples of the MRHDID when salmeterol was administered by the oral route to achieve high systemic exposures. No such effects occurred at an oral salmeterol dose approximately 10 times the MRHDID. (See Data.) The estimated risk of major birth defects and miscarriage for the indicated population 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 outcomes such as pre-eclampsia in the mother and prematurity, low birth weight, and small for gestational age in the neonate. Pregnant women should be closely monitored and medication adjusted as necessary to maintain optimal control of asthma.

Labor and Delivery: There are no human studies evaluating the effects of fluticasone propionate and salmeterol HFA during labor and delivery. Because of the potential for beta-agonist interference with uterine contractility, use of Fluticasone Propionate and Salmeterol HFA during labor should be restricted to those patients in whom the benefits clearly outweigh the risks. Data Human Data: Fluticasone Propionate: Following inhaled administration, fluticasone propionate was detected in the neonatal cord blood after delivery.

Animal Data: Fluticasone Propionate and Salmeterol: In an embryofetal development study with pregnant rats that received the combination of subcutaneous administration of fluticasone propionate and oral administration of salmeterol at doses of 0/1,000; 30/0; 10/100; 30/1,000; and 100/10,000 mcg/kg/day (as fluticasone propionate/salmeterol) during the period of organogenesis, findings were generally consistent with the individual monoproducts and there was no exacerbation of expected fetal effects. Omphalocele, increased embryofetal deaths, decreased body weight, and skeletal variations were observed in rat fetuses in the presence of maternal toxicity when combining fluticasone propionate at a dose approximately equivalent to the MRHDID (on a mcg/m 2 basis at a maternal subcutaneous dose of 100 mcg/kg/day) and salmeterol at a dose approximately 1,200 times the MRHDID (on a mcg/m 2 basis at a maternal oral dose of 10,000 mcg/kg/day).

The rat no observed adverse effect level (NOAEL) was observed when combining fluticasone propionate at a dose less than the MRHDID (on a mcg/m 2 basis at a maternal subcutaneous dose of 30 mcg/kg/day) and salmeterol at a dose approximately 12… [Excerpted — this section continues on DailyMed.]

🤰 Pregnancy ~3 min read ▾

8.1Pregnancy Risk Summary There are insufficient data on the use of fluticasone propionate and salmeterol HFA or individual monoproducts, fluticasone propionate and salmeterol xinafoate, in pregnant women. There are clinical considerations with the use of fluticasone propionate and salmeterol HFA in pregnant women. (See Clinical Considerations.) In animals, teratogenicity characteristic of corticosteroids, decreased fetal body weight and/or skeletal variations, in rats, mice, and rabbits, was observed with subcutaneously administered maternal toxic doses of fluticasone propionate less than the maximum recommended human daily inhaled dose (MRHDID) on a mcg/m 2 basis.

(See Data.) However, fluticasone propionate administered via inhalation to rats decreased fetal body weight but did not induce teratogenicity at a maternal toxic dose less than the MRHDID on a mcg/m 2 basis. (See Data.) Experience with oral corticosteroids suggests that rodents are more prone to teratogenic effects from corticosteroids than humans. Oral administration of salmeterol to pregnant rabbits caused teratogenicity characteristic of beta-adrenoceptor stimulation at maternal doses approximately 25 times the MRHDID on an AUC basis.

These adverse effects generally occurred at large multiples of the MRHDID when salmeterol was administered by the oral route to achieve high systemic exposures. No such effects occurred at an oral salmeterol dose approximately 10 times the MRHDID. (See Data.) The estimated risk of major birth defects and miscarriage for the indicated population 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 outcomes such as pre-eclampsia in the mother and prematurity, low birth weight, and small for gestational age in the neonate. Pregnant women should be closely monitored and medication adjusted as necessary to maintain optimal control of asthma.

Labor and Delivery: There are no human studies evaluating the effects of fluticasone propionate and salmeterol HFA during labor and delivery. Because of the potential for beta-agonist interference with uterine contractility, use of Fluticasone Propionate and Salmeterol HFA during labor should be restricted to those patients in whom the benefits clearly outweigh the risks. Data Human Data: Fluticasone Propionate: Following inhaled administration, fluticasone propionate was detected in the neonatal cord blood after delivery.

Animal Data: Fluticasone Propionate and Salmeterol: In an embryofetal development study with pregnant rats that received the combination of subcutaneous administration of fluticasone propionate and oral administration of salmeterol at doses of 0/1,000; 30/0; 10/100; 30/1,000; and 100/10,000 mcg/kg/day (as fluticasone propionate/salmeterol) during the period of organogenesis, findings were generally consistent with the individual monoproducts and there was no exacerbation of expected fetal effects. Omphalocele, increased embryofetal deaths, decreased body weight, and skeletal variations were observed in rat fetuses in the presence of maternal toxicity when combining fluticasone propionate at a dose approximately equivalent to the MRHDID (on a mcg/m 2 basis at a maternal subcutaneous dose of 100 mcg/kg/day) and salmeterol at a dose approximately 1,200 times the MRHDID (on a mcg/m 2 basis at a maternal oral dose of 10,000 mcg/kg/day).

The rat no observed adverse effect level (NOAEL) was observed when combining fluticasone propionate at a dose less than the MRHDID (on a mcg/m 2 basis at a maternal subcutaneous dose of 30 mcg/kg/day) and salmeterol at a dose approximately 120 times the MRHDID (on a mcg/m 2 basis at a maternal oral dose of 1,000 mcg/kg/day). In an embryofetal developm… [Excerpted — this section continues on DailyMed.]

🧒 Pediatric Use ~3 min read ▾

8.4Pediatric Use The safety and effectiveness of fluticasone propionate and salmeterol HFA have been established in pediatric patients aged 12 years and older. Use of fluticasone propionate and salmeterol HFA in this age group is supported by evidence from adequate and well-controlled studies in adults with additional data from thirty-eight (38) subjects aged 12 to 17 years were treated with fluticasone propionate and salmeterol HFA in U.S. pivotal clinical trials. Subjects in this age group demonstrated efficacy results similar to those observed in subjects aged 18 years and older.

There were no obvious differences in the type or frequency of adverse events reported in this age group compared with subjects aged 18 years and older. In a 12-week trial, the safety of fluticasone propionate and salmeterol HFA 45 mcg/21 mcg given as 2 inhalations twice daily was compared with that of fluticasone propionate 44 mcg HFA (FLOVENT HFA [fluticasone propionate inhalation aerosol]) 2 inhalations twice daily in 350 subjects aged 4 to 11 years with persistent asthma currently being treated with ICS. No new safety concerns were observed in children aged 4 to 11 years treated for 12 weeks with fluticasone propionate and salmeterol HFA 45 mcg/21 mcg compared with adults and adolescents aged 12 years and older.

Common adverse reactions (≥3%) seen in children aged 4 to 11 years treated with fluticasone propionate and salmeterol HFA 45 mcg/21 mcg but not reported in the adult and adolescent clinical trials of fluticasone propionate and salmeterol HFA include: pyrexia, cough, pharyngolaryngeal pain, rhinitis, and sinusitis [see Adverse Reactions ( 6.1 )] . This trial was not designed to assess the effect of salmeterol, a component of Fluticasone Propionate and Salmeterol HFA, on asthma hospitalizations and death in subjects aged 4 to 11 years.

The pharmacokinetics and pharmacodynamic effect on serum cortisol of 21 days of treatment with fluticasone propionate and salmeterol HFA 45 mcg/21 mcg (2 inhalations twice daily with or without a spacer) or ADVAIR DISKUS 100 mcg/50 mcg (1 inhalation twice daily) was evaluated in a trial of 31 children aged 4 to 11 years with mild asthma. Systemic exposure to salmeterol xinafoate was similar for fluticasone propionate and salmeterol HFA, fluticasone propionate and salmeterol HFA delivered with a spacer, and ADVAIR DISKUS while the systemic exposure to fluticasone propionate was lower with fluticasone propionate and salmeterol HFA compared with that of fluticasone propionate and salmeterol HFA delivered with a spacer or ADVAIR DISKUS.

There were reductions in serum cortisol from baseline in all treatment groups (14%, 22%, and 13% for fluticasone propionate and salmeterol HFA, fluticasone propionate and salmeterol HFA delivered with a spacer, and ADVAIR DISKUS, respectively) [see Clinical Pharmacology ( 12.2 , 12.3 )] . The safety and effectiveness of fluticasone propionate and salmeterol HFA in pediatric patients younger than 12 years have not been established. Effects on Growth ICS, including fluticasone propionate, a component of Fluticasone Propionate and Salmeterol HFA, may cause a reduction in growth velocity in children and adolescents [see Warnings and Precautions ( 5.14 )] .

The growth of pediatric patients receiving orally inhaled corticosteroids, including fluticasone propionate and salmeterol HFA, should be monitored. A 52-week placebo-controlled trial to assess the potential growth effects of fluticasone propionate inhalation powder (FLOVENT ROTADISK) at 50 and 100 mcg twice daily was conducted in the U.S. in 325 prepubescent children (244 males and 81 females) aged 4 to 11 years. The mean growth velocities at 52 weeks observed in the intent-to-treat population were 6.32 cm/year in the placebo group (n = 76), 6.07 cm/year in the 50-mcg group (n = 98), and 5.66 cm/year in the 100-mcg group (n = 89).

An imbalance in the proportion of children entering puberty between groups and a higher dropout rate… [Excerpted — this section continues on DailyMed.]

🧓 Geriatric Use 112 words ▾

8.5Geriatric Use Clinical trials of fluticasone propionate and salmeterol HFA did not include sufficient numbers of subjects aged 65 years and older to determine whether older subjects respond differently than younger subjects. In general, dose selection for an elderly patient should be cautious, usually starting at the low end of the dosing range, reflecting the greater frequency of decreased hepatic, renal, or cardiac function, and of concomitant disease or other drug therapy. In addition, as with other products containing beta 2 -agonists, special caution should be observed when using Fluticasone Propionate and Salmeterol HFA in geriatric patients who have concomitant cardiovascular disease that could be adversely affected by beta 2 -agonists.

🆘 Overdosage 213 words ▾

10 OVERDOSAGE No human overdosage data has been reported for fluticasone propionate and salmeterol HFA. Fluticasone Propionate and Salmeterol HFA contains both fluticasone propionate and salmeterol; therefore, the risks associated with overdosage for the individual components described below apply to Fluticasone Propionate and Salmeterol HFA. Treatment of overdosage consists of discontinuation of Fluticasone Propionate and Salmeterol HFA together with institution of appropriate symptomatic and/or supportive therapy.

The judicious use of a cardioselective beta-receptor blocker may be considered, bearing in mind that such medication can produce bronchospasm. Cardiac monitoring is recommended in cases of overdosage. Fluticasone Propionate Chronic overdosage of fluticasone propionate may result in signs/symptoms of hypercorticism [see Warnings and Precautions ( 5.8 )] .

Salmeterol The expected signs and symptoms with overdosage of salmeterol are those of excessive beta‑adrenergic stimulation and/or occurrence or exaggeration of any of the signs and symptoms of beta-adrenergic stimulation (e.g., seizures, angina, hypertension or hypotension, tachycardia with rates up to 200 beats/min, arrhythmias, nervousness, headache, tremor, muscle cramps, dry mouth, palpitation, nausea, dizziness, fatigue, malaise, insomnia, hyperglycemia, hypokalemia, metabolic acidosis). Overdosage with salmeterol can lead to clinically significant prolongation of the QTc interval, which can produce ventricular arrhythmias.

As with all inhaled sympathomimetic medicines, cardiac arrest and even death may be associated with an overdose of salmeterol.

🧬 Clinical Pharmacology ~3 min read ▾

12 CLINICAL PHARMACOLOGY

12.1Mechanism of Action Fluticasone Propionate and Salmeterol HFA Fluticasone Propionate and Salmeterol HFA contains both fluticasone propionate and salmeterol. The mechanisms of action described below for the individual components apply to Fluticasone Propionate and Salmeterol HFA. These drugs represent 2 different classes of medications (a synthetic corticosteroid and a LABA) that have different effects on clinical, physiologic, and inflammatory indices of asthma.

Fluticasone Propionate Fluticasone propionate is a synthetic trifluorinated corticosteroid with anti-inflammatory activity. Fluticasone propionate has been shown in vitro to exhibit a binding affinity for the human glucocorticoid receptor that is 18 times that of dexamethasone, almost twice that of beclomethasone-17-monopropionate (BMP), the active metabolite of beclomethasone dipropionate, and over 3 times that of budesonide. Data from the McKenzie vasoconstrictor assay in man are consistent with these results.

The clinical significance of these findings is unknown. Inflammation is an important component in the pathogenesis of asthma. Corticosteroids have been shown to have a wide range of actions on multiple cell types (e.g., mast cells, eosinophils, neutrophils, macrophages, lymphocytes) and mediators (e.g., histamine, eicosanoids, leukotrienes, cytokines) involved in inflammation.

These anti-inflammatory actions of corticosteroids contribute to their efficacy in asthma. Salmeterol Xinafoate Salmeterol is a selective LABA. In vitro studies show salmeterol to be at least 50 times more selective for beta 2 ‑adrenoceptors than albuterol.

Although beta 2 -adrenoceptors are the predominant adrenergic receptors in bronchial smooth muscle and beta 1 -adrenoceptors are the predominant receptors in the heart, there are also beta 2 -adrenoceptors in the human heart comprising 10% to 50% of the total beta-adrenoceptors. The precise function of these receptors has not been established, but their presence raises the possibility that even selective beta 2 -agonists may have cardiac effects. The pharmacologic effects of beta 2 -adrenoceptor agonist drugs, including salmeterol, are at least in part attributable to stimulation of intracellular adenyl cyclase, the enzyme that catalyzes the conversion of adenosine triphosphate (ATP) to cyclic-3′,5′-adenosine monophosphate (cyclic AMP).

Increased cyclic AMP levels cause relaxation of bronchial smooth muscle and inhibition of release of mediators of immediate hypersensitivity from cells, especially from mast cells. In vitro tests show that salmeterol is a potent and long-lasting inhibitor of the release of mast cell mediators, such as histamine, leukotrienes, and prostaglandin D 2 , from human lung. Salmeterol inhibits histamine-induced plasma protein extravasation and inhibits platelet-activating factor–induced eosinophil accumulation in the lungs of guinea pigs when administered by the inhaled route.

In humans, single doses of salmeterol administered via inhalation aerosol attenuate allergen-induced bronchial hyper-responsiveness.

12.2Pharmacodynamics Fluticasone Propionate and Salmeterol HFA Healthy Subjects: Cardiovascular Effects: Since systemic pharmacodynamic effects of salmeterol are not normally seen at the therapeutic dose, higher doses were used to produce measurable effects. Four (4) placebo-controlled crossover trials were conducted with healthy subjects: (1) a cumulative-dose trial using 42 to 336 mcg of salmeterol CFC inhalation aerosol given alone or as fluticasone propionate and salmeterol HFA 115 mcg/21 mcg, (2) a single-dose trial using 4 inhalations of fluticasone propionate and salmeterol HFA 230 mcg/21 mcg, salmeterol CFC inhalation aerosol 21 mcg, or fluticasone propionate CFC inhalation aerosol 220 mcg, (3) a single-dose trial using 8 inhalations of fluticasone propionate and salmeterol HFA 45 mcg/21 mcg, fluticasone propionate and salmeterol HFA 115 mcg/21 mcg, or fluticasone propi… [Excerpted — this section continues on DailyMed.]

🧬 Mechanism of Action ~2 min read ▾

12.1Mechanism of Action Fluticasone Propionate and Salmeterol HFA Fluticasone Propionate and Salmeterol HFA contains both fluticasone propionate and salmeterol. The mechanisms of action described below for the individual components apply to Fluticasone Propionate and Salmeterol HFA. These drugs represent 2 different classes of medications (a synthetic corticosteroid and a LABA) that have different effects on clinical, physiologic, and inflammatory indices of asthma.

Fluticasone Propionate Fluticasone propionate is a synthetic trifluorinated corticosteroid with anti-inflammatory activity. Fluticasone propionate has been shown in vitro to exhibit a binding affinity for the human glucocorticoid receptor that is 18 times that of dexamethasone, almost twice that of beclomethasone-17-monopropionate (BMP), the active metabolite of beclomethasone dipropionate, and over 3 times that of budesonide. Data from the McKenzie vasoconstrictor assay in man are consistent with these results.

The clinical significance of these findings is unknown. Inflammation is an important component in the pathogenesis of asthma. Corticosteroids have been shown to have a wide range of actions on multiple cell types (e.g., mast cells, eosinophils, neutrophils, macrophages, lymphocytes) and mediators (e.g., histamine, eicosanoids, leukotrienes, cytokines) involved in inflammation.

These anti-inflammatory actions of corticosteroids contribute to their efficacy in asthma. Salmeterol Xinafoate Salmeterol is a selective LABA. In vitro studies show salmeterol to be at least 50 times more selective for beta 2 ‑adrenoceptors than albuterol.

Although beta 2 -adrenoceptors are the predominant adrenergic receptors in bronchial smooth muscle and beta 1 -adrenoceptors are the predominant receptors in the heart, there are also beta 2 -adrenoceptors in the human heart comprising 10% to 50% of the total beta-adrenoceptors. The precise function of these receptors has not been established, but their presence raises the possibility that even selective beta 2 -agonists may have cardiac effects. The pharmacologic effects of beta 2 -adrenoceptor agonist drugs, including salmeterol, are at least in part attributable to stimulation of intracellular adenyl cyclase, the enzyme that catalyzes the conversion of adenosine triphosphate (ATP) to cyclic-3′,5′-adenosine monophosphate (cyclic AMP).

Increased cyclic AMP levels cause relaxation of bronchial smooth muscle and inhibition of release of mediators of immediate hypersensitivity from cells, especially from mast cells. In vitro tests show that salmeterol is a potent and long-lasting inhibitor of the release of mast cell mediators, such as histamine, leukotrienes, and prostaglandin D 2 , from human lung. Salmeterol inhibits histamine-induced plasma protein extravasation and inhibits platelet-activating factor–induced eosinophil accumulation in the lungs of guinea pigs when administered by the inhaled route.

In humans, single doses of salmeterol administered via inhalation aerosol attenuate allergen-induced bronchial hyper-responsiveness.

📦 How Supplied / Storage and Handling ~1 min read ▾

16 HOW SUPPLIED/STORAGE AND HANDLING Fluticasone Propionate and Salmeterol HFA is supplied in the following boxes of 1 as a pressurized aluminum canister fitted with a counter and supplied with a purple plastic actuator with a light purple cap: • Fluticasone Propionate and Salmeterol HFA 45 mcg/21 mcg: 12-g canister containing 120 actuations (NDC 66993-086-96) • Fluticasone Propionate and Salmeterol HFA 115 mcg/21 mcg: 12-g canister containing 120 actuations (NDC 66993-087-96) • Fluticasone Propionate and Salmeterol HFA 230 mcg/21 mcg: 12-g canister containing 120 actuations (NDC 66993-088-96) Each inhaler is packaged with a Patient Information leaflet.

The purple actuator supplied with Fluticasone Propionate and Salmeterol HFA should not be used with any other product canisters, and actuators from other products should not be used with a Fluticasone Propionate and Salmeterol HFA canister. Counter Fluticasone Propionate and Salmeterol HFA has a counter attached to the canister. The counter starts at 124 and counts down each time a spray is released.

The correct amount of medication in each actuation cannot be assured after the counter reads 000, even though the canister is not completely empty and will continue to operate. The inhaler should be discarded when the counter reads 000. Contents under Pressure Do not puncture.

Do not use or store near heat or open flame. Exposure to temperatures above 120°F may cause bursting. Never throw canister into fire or incinerator.

Storage Store at room temperature between 68°F and 77°F (20°C and 25°C); excursions permitted from 59°F to 86°F (15°C to 30°C) [See USP Controlled Room Temperature]. Store the inhaler with the mouthpiece down. For best results, the inhaler should be at room temperature before use.

📋 Description ~2 min read ▾

11 DESCRIPTION Fluticasone Propionate and Salmeterol HFA 45 mcg/21 mcg inhalation aerosol, Fluticasone Propionate and Salmeterol HFA inhalation aerosol 115 mcg/21 mcg, and Fluticasone Propionate and Salmeterol HFA inhalation aerosol 230 mcg/21 mcg are combinations of fluticasone propionate and salmeterol xinafoate. One active component of Fluticasone Propionate and Salmeterol HFA is fluticasone propionate, a corticosteroid having the chemical name S- (fluoromethyl) 6α,9-difluoro-11β,17-dihydroxy-16α-methyl-3-oxoandrosta-1,4-diene-17β-carbothioate, 17-propionate and the following chemical structure: Fluticasone propionate is a white powder with a molecular weight of 500.6, and the empirical formula is C 25 H 31 F 3 O 5 S.

It is practically insoluble in water, freely soluble in dimethyl sulfoxide and dimethylformamide, and slightly soluble in methanol and 95% ethanol. The other active component of Fluticasone Propionate and Salmeterol HFA is salmeterol xinafoate, a beta 2 -adrenergic bronchodilator. Salmeterol xinafoate is the racemic form of the 1-hydroxy-2-naphthoic acid salt of salmeterol.

It has the chemical name 4-hydroxy-α 1 -[[[6-(4-phenylbutoxy)hexyl]amino]methyl]-1,3-benzenedimethanol, 1-hydroxy-2-naphthalenecarboxylate and the following chemical structure: Salmeterol xinafoate is a white powder with a molecular weight of 603.8, and the empirical formula is C 25 H 37 NO 4 •C 11 H 8 O 3 . It is freely soluble in methanol; slightly soluble in ethanol, chloroform, and isopropanol; and sparingly soluble in water. Fluticasone Propionate and Salmeterol HFA is a purple plastic inhaler with a light purple cap containing a pressurized metered-dose aerosol canister fitted with a counter.

Each canister contains a microcrystalline suspension of micronized fluticasone propionate and micronized salmeterol xinafoate in propellant HFA-134a (1,1,1,2-tetrafluoroethane). It contains no other excipients. After priming, each actuation of the inhaler delivers 50, 125, or 250 mcg of fluticasone propionate and 25 mcg of salmeterol in 75 mg of suspension from the valve.

Each actuation delivers 45, 115, or 230 mcg of fluticasone propionate and 21 mcg of salmeterol from the actuator. Twenty-one micrograms (21 mcg) of salmeterol base is equivalent to 30.45 mcg of salmeterol xinafoate. The actual amount of drug delivered to the lung will depend on patient factors, such as the coordination between the actuation of the inhaler and inspiration through the delivery system.

Prime Fluticasone Propionate and Salmeterol HFA before using for the first time by releasing 4 sprays into the air away from the face, shaking well for 5 seconds before each spray. In cases where the inhaler has not been used for more than 4 weeks or when it has been dropped, prime the inhaler again by releasing 2 sprays into the air away from the face, shaking well for 5 seconds before each spray. Avoid spraying in eyes.

Fluticasone chemical structure Salmeterol chemical structure

💬 Information for Patients ~3 min read ▾

17 PATIENT COUNSELING INFORMATION Advise the patient to read the FDA-approved patient labeling (Patient Information and Instructions for Use). Serious Asthma-Related Events Inform patients with asthma that LABA when used alone increases the risk of asthma-related hospitalization or asthma-related death. Available data show that when ICS and LABA are used together, such as with Fluticasone Propionate and Salmeterol HFA, there is not a significant increase in the risk of these events. [See Warnings and Precautions ( 5.1 ).] Not for Acute Symptoms Inform patients that Fluticasone Propionate and Salmeterol HFA is not meant to relieve acute asthma symptoms and extra doses should not be used for that purpose.

Advise patients to treat acute asthma symptoms with an inhaled, short-acting beta 2 -agonist such as albuterol. Provide patients with such medication and instruct them in how it should be used. Instruct patients to seek medical attention immediately if they experience any of the following: • Decreasing effectiveness of inhaled, short-acting beta 2 -agonists • Need for more inhalations than usual of inhaled, short-acting beta 2 -agonists • Significant decrease in lung function as outlined by the physician Tell patients they should not stop therapy with Fluticasone Propionate and Salmeterol HFA without physician/provider guidance since symptoms may recur after discontinuation. [See Warnings and Precautions ( 5.2 ).] Do Not Use Additional Long-acting Beta 2 -agonists Instruct patients not to use other LABA for asthma. [See Warnings and Precautions ( 5.3 ).] Oropharyngeal Candidiasis Inform patients that localized infections with Candida albicans occurred in the mouth and pharynx in some patients.

If oropharyngeal candidiasis develops, treat it with appropriate local or systemic (i.e., oral) antifungal therapy while still continuing therapy with Fluticasone Propionate and Salmeterol HFA, but at times therapy with Fluticasone Propionate and Salmeterol HFA may need to be temporarily interrupted under close medical supervision. Advise patients to rinse the mouth with water without swallowing after inhalation to help reduce the risk of thrush. [See Warnings and Precautions ( 5.4 ).] Pneumonia Patients with COPD have a higher risk of pneumonia; instruct them to contact their healthcare providers if they develop symptoms of pneumonia. [See Warnings and Precautions ( 5.5 ).] Immunosuppression and Risk of Infections Warn patients who are on immunosuppressant doses of corticosteroids to avoid exposure to chickenpox or measles and, if exposed, to consult their physicians without delay.

Inform patients of potential worsening of existing tuberculosis; fungal, bacterial, viral, or parasitic infections; or ocular herpes simplex. [See Warnings and Precautions ( 5.6 ).] Hypercorticism and Adrenal Suppression Advise patients that Fluticasone Propionate and Salmeterol HFA may cause systemic corticosteroid effects of hypercorticism and adrenal suppression. Additionally, inform patients that deaths due to adrenal insufficiency have occurred during and after transfer from systemic corticosteroids. Patients should taper slowly from systemic corticosteroids if transferring to Fluticasone Propionate and Salmeterol HFA. [See Warnings and Precautions ( 5.8 ).] Hypersensitivity Reactions, including Anaphylaxis Advise patients that immediate hypersensitivity reactions (e.g., urticaria, angioedema, rash, bronchospasm, hypotension), including anaphylaxis, may occur after administration of Fluticasone Propionate and Salmeterol HFA.

Patients should discontinue Fluticasone Propionate and Salmeterol HFA if such reactions occur. [See Warnings and Precautions ( 5.11 ).] Risks Associated with Beta-agonist Therapy Inform patients of adverse effects associated with beta 2 -agonists, such as palpitations, chest pain, rapid heart rate, tremor, or nervousness. [See Warnings and Precautions ( 5.12 ).] Reduction in Bone Mineral Density Advise patients who are at an increased… [Excerpted — this section continues on DailyMed.]

🧬 Pharmacokinetics ~3 min read ▾

12.3Pharmacokinetics Absorption Fluticasone Propionate: Healthy Subjects: Fluticasone propionate acts locally in the lung; therefore, plasma levels do not predict therapeutic effect. Trials using oral dosing of labeled and unlabeled drug have demonstrated that the oral systemic bioavailability of fluticasone propionate is negligible (<1%), primarily due to incomplete absorption and presystemic metabolism in the gut and liver. In contrast, the majority of the fluticasone propionate delivered to the lung is systemically absorbed.

Three (3) single-dose, placebo-controlled, crossover trials were conducted in healthy subjects: (1) a trial using 4 inhalations of fluticasone propionate and salmeterol HFA 230 mcg/21 mcg, salmeterol CFC inhalation aerosol 21 mcg, or fluticasone propionate CFC inhalation aerosol 220 mcg, (2) a trial using 8 inhalations of fluticasone propionate and salmeterol HFA 45 mcg/21 mcg, fluticasone propionate and salmeterol HFA 115 mcg/21 mcg, or fluticasone propionate and salmeterol HFA 230 mcg/21 mcg, and (3) a trial using 4 inhalations of fluticasone propionate and salmeterol HFA 230 mcg/21 mcg; 2 inhalations of ADVAIR DISKUS 500 mcg/50 mcg; 4 inhalations of fluticasone propionate CFC inhalation aerosol 220 mcg; or 1,010 mcg of fluticasone propionate given intravenously.

Peak plasma concentrations of fluticasone propionate were achieved in 0.33 to 1.5 hours and those of salmeterol were achieved in 5 to 10 minutes. Peak plasma concentrations of fluticasone propionate (N = 20 subjects) following 8 inhalations of fluticasone propionate and salmeterol HFA 45 mcg/21 mcg, fluticasone propionate and salmeterol HFA 115 mcg/21 mcg, and fluticasone propionate and salmeterol HFA 230 mcg/21 mcg averaged 41, 108, and 173 pg/mL, respectively. Systemic exposure (N = 20 subjects) from 4 inhalations of fluticasone propionate and salmeterol HFA 230 mcg/21 mcg was 53% of the value from the individual inhaler for fluticasone propionate CFC inhalation aerosol and 42% of the value from the individual inhaler for salmeterol CFC inhalation aerosol.

Peak plasma concentrations from fluticasone propionate and salmeterol HFA for fluticasone propionate (86 versus 120 pg/mL) and salmeterol (170 versus 510 pg/mL) were significantly lower compared with individual inhalers. In 15 healthy subjects, systemic exposure to fluticasone propionate from 4 inhalations of fluticasone propionate and salmeterol HFA 230 mcg/21 mcg (920/84 mcg) and 2 inhalations of ADVAIR DISKUS 500 mcg/50 mcg (1,000/100 mcg) was similar between the 2 inhalers (i.e., 799 versus 832 pg•h/mL, respectively), but approximately half the systemic exposure from 4 inhalations of fluticasone propionate CFC inhalation aerosol 220 mcg (880 mcg, AUC = 1,543 pg•h/mL).

Similar results were observed for peak fluticasone propionate plasma concentrations (186 and 182 pg/mL from fluticasone propionate and salmeterol HFA and ADVAIR DISKUS, respectively, and 307 pg/mL from the fluticasone propionate CFC inhalation aerosol). Absolute bioavailability of fluticasone propionate was 5.3% and 5.5% following administration of fluticasone propionate and salmeterol HFA and ADVAIR DISKUS, respectively. Subjects with Asthma: A double-blind crossover trial was conducted in 13 adult subjects with asthma to evaluate the steady-state pharmacokinetics of fluticasone propionate and salmeterol following administration of 2 inhalations of fluticasone propionate and salmeterol HFA 115 mcg/21 mcg twice daily or 1 inhalation of ADVAIR DISKUS 250 mcg/50 mcg twice daily for 4 weeks.

Systemic exposure (AUC) to fluticasone propionate was similar for fluticasone propionate and salmeterol HFA (274 pg•h/mL [95% CI: 150, 502]) and ADVAIR DISKUS (338 pg•h/mL [95% CI: 197, 581]). The effect of 21 days of treatment with fluticasone propionate and salmeterol HFA 45 mcg/21 mcg (2 inhalations twice daily with or without a spacer) or ADVAIR DISKUS 100 mcg/50 mcg (1 inhalation twice daily) was evaluated in a trial of 31 childre… [Excerpted — this section continues on DailyMed.]

🧬 Pharmacodynamics ~3 min read ▾

12.2Pharmacodynamics Fluticasone Propionate and Salmeterol HFA Healthy Subjects: Cardiovascular Effects: Since systemic pharmacodynamic effects of salmeterol are not normally seen at the therapeutic dose, higher doses were used to produce measurable effects. Four (4) placebo-controlled crossover trials were conducted with healthy subjects: (1) a cumulative-dose trial using 42 to 336 mcg of salmeterol CFC inhalation aerosol given alone or as fluticasone propionate and salmeterol HFA 115 mcg/21 mcg, (2) a single-dose trial using 4 inhalations of fluticasone propionate and salmeterol HFA 230 mcg/21 mcg, salmeterol CFC inhalation aerosol 21 mcg, or fluticasone propionate CFC inhalation aerosol 220 mcg, (3) a single-dose trial using 8 inhalations of fluticasone propionate and salmeterol HFA 45 mcg/21 mcg, fluticasone propionate and salmeterol HFA 115 mcg/21 mcg, or fluticasone propionate and salmeterol HFA 230 mcg/21 mcg, and (4) a single-dose trial using 4 inhalations of fluticasone propionate and salmeterol HFA 230 mcg/21 mcg; 2 inhalations of ADVAIR DISKUS 500 mcg/50 mcg; 4 inhalations of fluticasone propionate CFC inhalation aerosol 220 mcg; or 1,010 mcg of fluticasone propionate given intravenously.

In these trials pulse rate, blood pressure, QTc interval, glucose, and/or potassium were measured. Comparable or lower effects were observed for fluticasone propionate and salmeterol HFA compared with ADVAIR DISKUS or salmeterol alone. The effect of salmeterol on pulse rate and potassium was not altered by the presence of different amounts of fluticasone propionate in fluticasone propionate and salmeterol HFA.

Hypothalamic-Pituitary-Adrenal Axis Effects: The potential effect of salmeterol on the effects of fluticasone propionate on the HPA axis was also evaluated in 3 of these trials. Compared with fluticasone propionate CFC inhalation aerosol, fluticasone propionate and salmeterol HFA had less effect on 24-hour urinary cortisol excretion and less or comparable effect on 24-hour serum cortisol. In these crossover trials in healthy subjects, fluticasone propionate and salmeterol HFA and ADVAIR DISKUS had similar effects on urinary and serum cortisol.

Subjects with Asthma: Cardiovascular Effects: In clinical trials with fluticasone propionate and salmeterol HFA in adult and adolescent subjects aged 12 years and older with asthma, systemic pharmacodynamic effects of salmeterol (pulse rate, blood pressure, QTc interval, potassium, and glucose) were similar to or slightly lower in patients treated with fluticasone propionate and salmeterol HFA compared with patients treated with salmeterol CFC inhalation aerosol 21 mcg. In 61 adult and adolescent subjects with asthma given fluticasone propionate and salmeterol HFA (45 mcg/21 mcg or 115 mcg/21 mcg), continuous 24-hour electrocardiographic monitoring was performed after the first dose and after 12 weeks of twice-daily therapy, and no clinically significant dysrhythmias were noted.

The effect of 21 days of treatment with fluticasone propionate and salmeterol HFA 45 mcg/21 mcg (2 inhalations twice daily with or without a spacer) or ADVAIR DISKUS 100 mcg/50 mcg (1 inhalation twice daily) was evaluated in 31 children aged 4 to 11 years with mild asthma. There were no notable changes from baseline for QTc, heart rate, or systolic and diastolic blood pressure. Hypothalamic-Pituitary-Adrenal Axis Effects: A 4-way crossover trial in 13 subjects with asthma compared pharmacodynamics at steady state following 4 weeks of twice-daily treatment with 2 inhalations of fluticasone propionate and salmeterol HFA 115 mcg/21 mcg, 1 inhalation of ADVAIR DISKUS 250 mcg/50 mcg, 2 inhalations of fluticasone propionate HFA inhalation aerosol 110 mcg, and placebo.

No significant differences in serum cortisol AUC were observed between active treatments and placebo. Mean 12-hour serum cortisol AUC ratios comparing active treatment with placebo ranged from 0.9 to 1.2. No statistically or clinically significant incre… [Excerpted — this section continues on DailyMed.]

🔬 Clinical Studies ~3 min read ▾

14 CLINICAL STUDIES Fluticasone propionate and salmeterol HFA has been studied in subjects with asthma aged 12 years and older. Fluticasone propionate and salmeterol HFA has not been studied in subjects younger than 12 years or in subjects with COPD. In clinical trials comparing fluticasone propionate and salmeterol HFA with its individual components, improvements in most efficacy endpoints were greater with fluticasone propionate and salmeterol HFA than with the use of either fluticasone propionate or salmeterol alone.

In addition, clinical trials showed comparable results between fluticasone propionate and salmeterol HFA and ADVAIR DISKUS.

14.1Trials Comparing Fluticasone Propionate and Salmeterol HFA with Fluticasone Propionate Alone or Salmeterol Alone Four (4) double-blind, parallel-group clinical trials were conducted with fluticasone propionate and salmeterol HFA in 1,517 adult and adolescent subjects (aged 12 years and older, mean baseline FEV 1 65% to 75% of predicted normal) with asthma that was not optimally controlled on their current therapy. All metered-dose inhaler treatments were inhalation aerosols given as 2 inhalations twice daily, and other maintenance therapies were discontinued.

Trial 1: Clinical Trial with Fluticasone Propionate and Salmeterol HFA 45 mcg/21 mcg This placebo-controlled, 12-week, U.S. trial compared fluticasone propionate and salmeterol HFA 45 mcg/21 mcg with fluticasone propionate CFC inhalation aerosol 44 mcg or salmeterol CFC inhalation aerosol 21 mcg, each given as 2 inhalations twice daily. The primary efficacy endpoints were predose FEV 1 and withdrawals due to worsening asthma. This trial was stratified according to baseline asthma therapy: subjects using beta-agonists (albuterol alone [n = 142], salmeterol [n = 84], or ICS [n = 134] [daily doses of beclomethasone dipropionate 252 to 336 mcg; budesonide 400 to 600 mcg; flunisolide 1,000 mcg; fluticasone propionate inhalation aerosol 176 mcg; fluticasone propionate inhalation powder 200 mcg; or triamcinolone acetonide 600 to 800 mcg]).

Baseline FEV 1 measurements were similar across treatments: fluticasone propionate and salmeterol HFA 45 mcg/21 mcg,

2.29 L; fluticasone propionate 44 mcg,

2.20 L; salmeterol,

2.33 L; and placebo,

2.27L. Predefined withdrawal criteria for lack of efficacy, an indicator of worsening asthma, were utilized for this placebo-controlled trial. Worsening asthma was defined as a clinically important decrease in FEV 1 or PEF, increase in use of VENTOLIN (albuterol, USP) Inhalation Aerosol, increase in night awakenings due to asthma, emergency intervention or hospitalization due to asthma, or requirement for asthma medicine not allowed by the protocol.

As shown in Table 3, statistically significantly fewer subjects receiving fluticasone propionate and salmeterol HFA 45 mcg/21 mcg were withdrawn due to worsening asthma compared with salmeterol and placebo. Fewer subjects receiving fluticasone propionate and salmeterol HFA 45 mcg/21 mcg were withdrawn due to worsening asthma compared with fluticasone propionate 44 mcg; however, the difference was not statistically significant. Table 3.

Percent of Subjects Withdrawn due to Worsening Asthma in Subjects Previously Treated with Beta2-agonists (Albuterol or Salmeterol) or Inhaled Corticosteroids (Trial 1) Fluticasone Propionate and Salmeterol HFA 45 mcg/21 mcg (n = 92) Fluticasone Propionate CFC Inhalation Aerosol 44 mcg (n = 89) Salmeterol CFC Inhalation Aerosol 21 mcg (n = 92) Placebo HFA Inhalation Aerosol (n = 87) 2% 8% 25% 28% The FEV 1 results are displayed in Figure 1. Because this trial used predetermined criteria for worsening asthma, which caused more subjects in the placebo group to be withdrawn, FEV 1 results at Endpoint (last available FEV 1 result) are also provided.

Subjects receiving fluticasone propionate and salmeterol HFA 45 mcg/21 mcg had significantly greater improvements in FEV 1 (0.58 L, 27%) compared with fluticasone propionate 44 mcg (0.36 L,… [Excerpted — this section continues on DailyMed.]

🧪 Nonclinical Toxicology ~2 min read ▾

13 NONCLINICAL TOXICOLOGY

13.1Carcinogenesis, Mutagenesis, Impairment of Fertility Fluticasone Propionate Fluticasone propionate demonstrated no tumorigenic potential in mice at oral doses up to 1,000 mcg/kg (approximately 5 times the MRHDID on a mcg/m 2 basis) for 78 weeks or in rats at inhalation doses up to 57 mcg/kg (approximately 0.5 times the MRHDID on a mcg/m 2 basis) for 104 weeks. Fluticasone propionate did not induce gene mutation in prokaryotic or eukaryotic cells in vitro. No significant clastogenic effect was seen in cultured human peripheral lymphocytes in vitro or in the in vivo mouse micronucleus test.

Fertility and reproductive performance were unaffected in male and female rats at subcutaneous doses up to 50 mcg/kg (approximately 0.5 times the MRHDID for adults on a mcg/m 2 basis). Salmeterol In an 18-month carcinogenicity study in CD-mice, salmeterol at oral doses of 1,400 mcg/kg and above (approximately 10 times the MRHDID based on comparison of the plasma AUCs) caused a dose-related increase in the incidence of smooth muscle hyperplasia, cystic glandular hyperplasia, leiomyomas of the uterus, and ovarian cysts.

No tumors were seen at 200 mcg/kg (approximately 2 times the MRHDID for adults based on comparison of the AUCs). In a 24-month oral and inhalation carcinogenicity study in Sprague Dawley rats, salmeterol caused a dose-related increase in the incidence of mesovarian leiomyomas and ovarian cysts at doses of 680 mcg/kg and above (approximately 80 times the MRHDID on a mcg/m 2 basis). No tumors were seen at 210 mcg/kg (approximately 25 times the MRHDID on a mcg/m 2 basis).

These findings in rodents are similar to those reported previously for other beta-adrenergic agonist drugs. The relevance of these findings to human use is unknown. Salmeterol produced no detectable or reproducible increases in microbial and mammalian gene mutation in vitro.

No clastogenic activity occurred in vitro in human lymphocytes or in vivo in a rat micronucleus test. Fertility and reproductive performance were unaffected in male and female rats at oral doses up to 2,000 mcg/kg (approximately 230 times the MRHDID for adults on a mcg/m 2 basis).

13.2Animal Toxicology and/or Pharmacology Studies in laboratory animals (minipigs, rodents, and dogs) have demonstrated the occurrence of cardiac arrhythmias and sudden death (with histologic evidence of myocardial necrosis) when beta-agonists and methylxanthines are administered concurrently. The clinical relevance of these findings is unknown.

📄 Carcinogenesis, Mutagenesis, Impairment of Fertility ~2 min read ▾

13.1Carcinogenesis, Mutagenesis, Impairment of Fertility Fluticasone Propionate Fluticasone propionate demonstrated no tumorigenic potential in mice at oral doses up to 1,000 mcg/kg (approximately 5 times the MRHDID on a mcg/m 2 basis) for 78 weeks or in rats at inhalation doses up to 57 mcg/kg (approximately 0.5 times the MRHDID on a mcg/m 2 basis) for 104 weeks. Fluticasone propionate did not induce gene mutation in prokaryotic or eukaryotic cells in vitro. No significant clastogenic effect was seen in cultured human peripheral lymphocytes in vitro or in the in vivo mouse micronucleus test.

Fertility and reproductive performance were unaffected in male and female rats at subcutaneous doses up to 50 mcg/kg (approximately 0.5 times the MRHDID for adults on a mcg/m 2 basis). Salmeterol In an 18-month carcinogenicity study in CD-mice, salmeterol at oral doses of 1,400 mcg/kg and above (approximately 10 times the MRHDID based on comparison of the plasma AUCs) caused a dose-related increase in the incidence of smooth muscle hyperplasia, cystic glandular hyperplasia, leiomyomas of the uterus, and ovarian cysts.

No tumors were seen at 200 mcg/kg (approximately 2 times the MRHDID for adults based on comparison of the AUCs). In a 24-month oral and inhalation carcinogenicity study in Sprague Dawley rats, salmeterol caused a dose-related increase in the incidence of mesovarian leiomyomas and ovarian cysts at doses of 680 mcg/kg and above (approximately 80 times the MRHDID on a mcg/m 2 basis). No tumors were seen at 210 mcg/kg (approximately 25 times the MRHDID on a mcg/m 2 basis).

These findings in rodents are similar to those reported previously for other beta-adrenergic agonist drugs. The relevance of these findings to human use is unknown. Salmeterol produced no detectable or reproducible increases in microbial and mammalian gene mutation in vitro.

No clastogenic activity occurred in vitro in human lymphocytes or in vivo in a rat micronucleus test. Fertility and reproductive performance were unaffected in male and female rats at oral doses up to 2,000 mcg/kg (approximately 230 times the MRHDID for adults on a mcg/m 2 basis).

📄 Patient Package Insert ~3 min read ▾

PATIENT INFORMATION Fluticasone Propionate and Salmeterol HFA inhalation aerosol for oral inhalation use What is Fluticasone Propionate and Salmeterol HFA? • Fluticasone Propionate and Salmeterol HFA combines the inhaled corticosteroid (ICS) medicine fluticasone propionate and the long-acting beta 2 -adrenergic agonist (LABA) medicine salmeterol. o ICS medicines such as fluticasone propionate help to decrease inflammation in the lungs. Inflammation in the lungs can lead to breathing problems. o LABA medicines such as salmeterol help the muscles around the airways in your lungs stay relaxed to prevent symptoms, such as wheezing, cough, chest tightness, and shortness of breath.

These symptoms can happen when the muscles around the airways tighten. This makes it hard to breathe. • Fluticasone Propionate and Salmeterol HFA is not used to relieve sudden breathing problems and will not replace a rescue inhaler. • It is not known if Fluticasone Propionate and Salmeterol HFA is safe and effective in children younger than 12 years of age. • Fluticasone Propionate and Salmeterol HFA is used for asthma as follows: o Fluticasone Propionate and Salmeterol HFA is a prescription medicine used to control symptoms of asthma and to prevent symptoms such as wheezing in adults and adolescents aged 12 years and older. o Fluticasone Propionate and Salmeterol HFA contains salmeterol, the same medicine found in SEREVENT DISKUS (salmeterol xinafoate inhalation powder).

LABA medicines such as salmeterol when used alone increase the risk of hospitalizations and death from asthma problems. Fluticasone Propionate and Salmeterol HFA contains an ICS and a LABA. When an ICS and LABA are used together, there is not a significant increased risk in hospitalizations and death from asthma problems. o Fluticasone Propionate and Salmeterol HFA is not for adults and adolescents with asthma who are well controlled with an asthma control medicine, such as a low to medium dose of an ICS medicine.

Fluticasone Propionate and Salmeterol HFA is for adults and adolescents with asthma who need both an ICS and LABA medicine. Do not use Fluticasone Propionate and Salmeterol HFA: • to relieve sudden breathing problems. • as a rescue inhaler. • if you are allergic to fluticasone propionate, salmeterol, or any of the ingredients in Fluticasone Propionate and Salmeterol HFA. See the end of this Patient Information for a complete list of ingredients in Fluticasone Propionate and Salmeterol HFA.

Before using Fluticasone Propionate and Salmeterol HFA, tell your healthcare provider about all of your medical conditions, including if you: • have heart problems. • have high blood pressure. • have seizures. • have thyroid problems. • have diabetes. • have liver problems. • have weak bones (osteoporosis). • have an immune system problem. • have or have had eye problems such as glaucoma, increased pressure in your eye, cataracts, or other changes in vision. • have any type of viral, bacterial, or fungal infection. • are exposed to chickenpox or measles. • are pregnant or plan to become pregnant.

It is not known if Fluticasone Propionate and Salmeterol HFA may harm your unborn baby. • are breastfeeding. It is not known if the medicines in Fluticasone Propionate and Salmeterol HFA pass into your milk and if they can harm your baby. Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

Fluticasone Propionate and Salmeterol HFA and certain other medicines may interact with each other. This may cause serious side effects. Especially tell your healthcare provider if you take antifungal or anti-HIV medicines.

Know the medicines you take. Keep a list of them to show your healthcare provider and pharmacist when you get a new medicine. How should I use Fluticasone Propionate and Salmeterol HFA?

Read the step-by-step instructions for using Fluticasone Propionate and Salmeterol HFA at the end of this Pati… [Excerpted — this section continues on DailyMed.]

📖 Instructions for Use ~3 min read ▾

INSTRUCTIONS FOR USE Fluticasone Propionate and Salmeterol HFA inhalation aerosol for oral inhalation use Your Fluticasone Propionate and Salmeterol HFA inhaler Figure A • The metal canister holds the medicine. See Figure A. • The metal canister has a counter to show how many sprays of medicine you have left. The number shows through a window in the back of the purple plastic actuator.

See Figure A. • The counter starts at 124 . The number will count down by 1 each time you spray the inhaler. The counter will stop counting at 000 . • Do not try to change the numbers or take the counter off the metal canister.

The counter cannot be reset, and it is permanently attached to the metal canister. • The purple plastic actuator sprays the medicine from the metal canister. The plastic actuator has a light purple protective cap that covers the mouthpiece. See Figure A.

Keep the protective cap on the mouthpiece when the metal canister is not in use. • Do not use the plastic actuator with a canister of medicine from any other inhaler. • Do not use a Fluticasone Propionate and Salmeterol HFA metal canister with an actuator from any other inhaler. Before using your Fluticasone Propionate and Salmeterol HFA inhaler • The inhaler should be at room temperature before you use it. Priming your Fluticasone Propionate and Salmeterol HFA inhaler Figure B Figure C Figure D Before you use Fluticasone Propionate and Salmeterol HFA for the first time, you must prime the inhaler so that you will get the right amount of medicine when you use it. • To take the cap off the mouthpiece, squeeze the sides of the cap and pull it straight out.

See Figure B. • Shake the inhaler well for 5 seconds. • Spray the inhaler 1 time into the air away from your face. Avoid spraying in eyes. See Figure C. • Shake and spray the inhaler like this 3 more times to finish priming it.

The counter should now read 120 . See Figure D. • You must prime your inhaler again if you have not used it in more than 4 weeks or if you have dropped it. To take the cap off the mouthpiece, squeeze the sides of the cap and pull it straight out.

Shake the inhaler well for 5 seconds. Then spray it 1 time into the air away from your face. Shake and spray the inhaler like this 1 more time to finish priming it.

How to use your Fluticasone Propionate and Salmeterol HFA inhaler Follow these steps every time you use Fluticasone Propionate and Salmeterol HFA. Figure E Figure F Figure G Figure H Step 1. Make sure the metal canister fits firmly in the plastic actuator.

The counter should show through the window in the actuator. To take the cap off the mouthpiece, squeeze the sides of the cap and pull it straight out. Look inside the mouthpiece for foreign objects and take out any you see.

Step 2. Hold the inhaler with the mouthpiece down and shake it well for 5 seconds. See Figure E.

Step 3. Breathe out through your mouth and push as much air from your lungs as you can. See Figure F.

Step 4. Put the mouthpiece in your mouth and close your lips around it. Push the top of the metal canister firmly all the way down while you breathe in deeply and slowly through your mouth.

See Figure G. Step 5. After the spray comes out, take your finger off the metal canister.

After you have breathed in all the way, take the inhaler out of your mouth and close your mouth. Step 6. Hold your breath for about 10 seconds, or for as long as is comfortable.

Breathe out slowly as long as you can. Wait about 30 seconds and shake the inhaler well for 5 seconds. Repeat Step 2 through Step 6.

Step 7. Rinse your mouth with water after breathing in the medicine. Spit out the water.

Do not swallow it. See Figure H. Step 8.

Put the cap back on the mouthpiece after you finish using the inhaler. Make sure it snaps firmly into place. Cleaning your Fluticasone Propionate and Salmeterol HFA inhaler Figure I Figure J Clean your inhaler at least 1 time each week after your evening dose.

You may not see any medicine build-up on the inhaler, but it… [Excerpted — this section continues on DailyMed.]

📄 Package Label / Principal Display Panel ~1 min read ▾

PRINCIPAL DISPLAY PANEL NDC 66993-086-96 Fluticasone Propionate and Salmeterol HFA Inhalation Aerosol 45 mcg/21 mcg PRASCO For oral inhalation with Fluticasone Propionate and Salmeterol HFA actuator only. Contents: Each canister contains a microcrystalline suspension of fluticasone propionate and salmeterol xinafoate in propellant HFA-134a (1,1,1,2-tetrafluoroethane). Each actuation delivers 45 mcg of fluticasone propionate and 30.45 mcg of salmeterol xinafoate equivalent to 21 mcg of salmeterol base from the mouthpiece.

See prescribing information for dosage information. R X Only 120 Metered Actuations Net Wt. 12 g 62000000083185 Rev.

10/22 Fluticasone Propionate and Salmeterol HFA 45 mcg-21 mcg 120 dose carton

PRINCIPAL DISPLAY PANEL NDC 66993-087-96 Fluticasone Propionate and Salmeterol HFA Inhalation Aerosol 115 mcg/21 mcg PRASCO For oral inhalation with Fluticasone Propionate and Salmeterol HFA actuator only. Contents: Each canister contains a microcrystalline suspension of fluticasone propionate and salmeterol xinafoate in propellant HFA-134a (1,1,1,2-tetrafluoroethane). Each actuation delivers 115 mcg of fluticasone propionate and 30.45 mcg of salmeterol xinafoate equivalent to 21 mcg of salmeterol base from the mouthpiece.

See prescribing information for dosage information. R X Only 120 Metered Actuations Net Wt. 12 g 62000000083187 Rev.

10/22 Fluticasone Propionate and Salmeterol HFA 115 mcg-21 mcg 120 dose carton

PRINCIPAL DISPLAY PANEL NDC 66993-088-96 Fluticasone Propionate and Salmeterol HFA Inhalation Aerosol 230 mcg/21 mcg PRASCO For oral inhalation with Fluticasone Propionate and Salmeterol HFA actuator only. Contents: Each canister contains a microcrystalline suspension of fluticasone propionate and salmeterol xinafoate in propellant HFA-134a (1,1,1,2-tetrafluoroethane). Each actuation delivers 230 mcg of fluticasone propionate and 30.45 mcg of salmeterol xinafoate equivalent to 21 mcg of salmeterol base from the mouthpiece.

See prescribing information for dosage information. R X Only 120 Metered Actuations Net Wt. 12 g 6200000083189 Rev.

10/22 Fluticasone Propionate and Salmeterol HFA 230 mcg-21 mcg 120 dose carton

Source: FDA Structured Product Labeling, mirrored from DailyMed / openFDA. Prefer the government’s original formatting? View this label on DailyMed ↗

Medicaid utilization & spend

📍 This exact package only: Medicaid data is reported per full 11-digit NDC — labeler, product and pack size — so every number here is for this package alone, not the drug overall. Other pack sizes report separately.
💊 Pharmacy benefit only: These are Medicaid outpatient pharmacy claims, billed by NDC. They exclude the medical benefit — clinic- or hospital-administered drugs billed under HCPCS J-codes — so drugs used mostly that way (e.g. Avastin, Lucentis, Keytruda) can look low or missing here. That’s expected, not an error.
📅 Q1 2025 – Q1 2026 · 5 quarters of data
ⓘ The newest quarter is usually incomplete when first published; states restate recent quarters in later CMS releases, so the latest figures typically revise upward. State coverage-policy changes can also shift quarter-to-quarter totals.
Prescriptions last 4 qtrs
18.6K
Units reimbursed last 4 qtrs
240.2K
Gross reimbursed last 4 qtrs
$7.81M
Avg / prescription
$420.88
Avg / unit
$32.5200
Latest quarter Q1 2026
4KRx
Medicaid pays / g
$32.5200
gross reimbursed
vs
NADAC / g
$26.7460
acquisition cost
=
Spread
+$5.7740
+22% vs cost
What Medicaid paid per g (before rebates; includes the pharmacy’s dispensing fee) compared with NADAC — the average price pharmacies pay to buy the drug. A positive spread means Medicaid reimbursed more than the purchase price, before manufacturer rebates.
Fee-for-service vs managed care ⓘ
13% FFS 87% MCO
Fee-for-service · 2,387 Rx Managed care · 16,171 Rx
State Medicaid map
Alaska: 1,188 units · 162 per 100k residents AK Maine: no data reported ME Washington: 55,992 units · 717 per 100k residents WA Idaho: no data reported ID Montana: no data reported MT North Dakota: no data reported ND Minnesota: 324 units · 5.6 per 100k residents MN Wisconsin: no data reported WI Michigan: 372 units · 3.7 per 100k residents MI New York: 1,020 units · 5.2 per 100k residents NY Vermont: no data reported VT New Hampshire: 3,864 units · 276 per 100k residents NH Oregon: 3,072 units · 72.6 per 100k residents OR Nevada: 1,032 units · 32.3 per 100k residents NV Wyoming: no data reported WY South Dakota: 3,456 units · 376 per 100k residents SD Iowa: 1,860 units · 58.0 per 100k residents IA Illinois: 2,556 units · 20.4 per 100k residents IL Indiana: 192 units · 2.8 per 100k residents IN Ohio: no data reported OH Pennsylvania: 1,704 units · 13.1 per 100k residents PA New Jersey: 3,456 units · 37.2 per 100k residents NJ Massachusetts: no data reported MA California: 1,680 units · 4.3 per 100k residents CA Utah: 708 units · 20.7 per 100k residents UT Colorado: 156 units · 2.7 per 100k residents CO Nebraska: no data reported NE Missouri: 1,068 units · 17.2 per 100k residents MO Kentucky: no data reported KY West Virginia: no data reported WV Virginia: 2,520 units · 28.9 per 100k residents VA Maryland: 8,352 units · 135 per 100k residents MD Connecticut: no data reported CT Rhode Island: 2,820 units · 258 per 100k residents RI Arizona: 612 units · 8.2 per 100k residents AZ New Mexico: 372 units · 17.6 per 100k residents NM Kansas: 6,132 units · 209 per 100k residents KS Arkansas: no data reported AR Tennessee: 6,408 units · 89.9 per 100k residents TN North Carolina: 3,156 units · 29.1 per 100k residents NC South Carolina: 864 units · 16.1 per 100k residents SC Delaware: no data reported DE Oklahoma: 25,752 units · 635 per 100k residents OK Louisiana: 24,612 units · 538 per 100k residents LA Mississippi: 5,976 units · 203 per 100k residents MS Alabama: 1,476 units · 28.9 per 100k residents AL Georgia: 1,872 units · 17.0 per 100k residents GA D.C.: no data reported DC Hawaii: 5,064 units · 353 per 100k residents HI Texas: 59,628 units · 195 per 100k residents TX Florida: 732 units · 3.2 per 100k residents FL
Units reimbursed · per 100k residents
2.7717
gray = no data reported ⓘ
Colors are per 100,000 residents, so big states don’t automatically dominate. Tap or hover a state for its actual totals.
Tap or hover a state
…for its Medicaid breakdown
🏆 Top states by units · per 100k residents
1 Washington 717 /100k
2 Oklahoma 635 /100k
3 Louisiana 538 /100k
4 South Dakota 376 /100k
5 Hawaii 353 /100k
6 New Hampshire 276 /100k
7 Rhode Island 258 /100k
8 Kansas 209 /100k
National units — by quarter
💵 About the dollar figures: “reimbursed” is what Medicaid paid pharmacies before confidential manufacturer rebates, so the program’s real net cost is lower than these numbers. Fee-for-service and managed-care claims are combined unless split above. Source: CMS State Drug Utilization Data; per-100k rates use 2023 Census population estimates.
← 66993-0087-96 · Prasco 66993-0100-06 · Prasco →
For educational and professional reference only — not medical advice. Pricing reflects published NADAC and CMS ASP (free public data) and may differ from your acquisition cost; always verify before billing or dispensing.