Fluticasone Propionate

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The following indications for FLUTICASONE PROPIONATE (fluticasone propionate) have been approved by the FDA:

Indications:
Allergic conjunctivitis
Allergic dermatitis
Allergic rhinitis
Atopic dermatitis
Chronic non-allergic rhinitis
Contact dermatitis
Cutaneous T-cell lymphoma
Discoid lupus erythematosus
Genital organ pruritus
Granuloma annulare
Lichen simplex chronicus
Maintenance therapy for asthma
Plaque psoriasis
Pruritus ani
Pruritus of skin
Pyoderma gangrenosum
Scalp psoriasis
Seborrheic dermatitis
Skin inflammation

Professional Synonyms:
Allergy eye itch
Atopic conjunctivitis
Atopic eczema
Chronic nonallergic rhinitis
Circumscribed neurodermatitis
Dermatitis seborrheica
Dermatitis venenata
Dermatitis
Disseminated neurodermatitis
Dyssebacea
Dyssebacia
Genital pruritus
Itchy eyes due to allergies
Itchy skin eruption
Lichen annularis
Ocular itching due to allergies
Primary cutaneous T-cell lymphoma
Pruritic dermatitis
Seborrhea corporis
Seborrheic eczema
Small cerebriform cell lymphoma
Therapy to achieve long-term asthma control
Unna's disease
Vidal's disease

The following dosing information is available for FLUTICASONE PROPIONATE (fluticasone propionate):

Dosing
Administration
FLUTICASONE PROPIONATE
FLUTICASONE PROPIONATE

The nasal inhaler delivers about 50 mcg of fluticasone propionate per metered spray. The commercially available preparation delivers about 120 metered sprays per 16-g bottle; the container should be discarded after the labeled number of actuations have been used since the correct dose per inhalation cannot be assured if used for additional doses. Dosage of intranasal fluticasone propionate should be adjusted according to individual requirements and response; the lowest effective dosage should be used in order to minimize potential systemic effects of the drug.

(See Cautions: Hypothalamic-Pituitary-Adrenal (HPA) Axis Suppression.) The maximum daily dosage of intranasal fluticasone propionate should not exceed 100 mcg in each nostril (total of 200 mcg daily).

Unless otherwise stated, the dose of fluticasone propionate administered as an aerosol via metered-dose inhaler with a hydrofluoroalkane (HFA) propellant is expressed as the amount of drug delivered from the actuator of the inhaler per metered spray; the dose of fluticasone propionate (and of salmeterol in the combination preparation Advair(R)) administered as an oral inhalation powder is expressed as the nominal (labeled) dose contained in each foil-wrapped blister. The manufacturer states that spacer devices should not be used with Advair(R) or Flovent(R) Diskus(R).

Each actuation of the commercially available fluticasone propionate HFA oral inhalation aerosol labeled as containing 44, 110, or 220 mcg of fluticasone propionate per metered spray delivers 50, 125, or 250 mcg from the valve, respectively, and 44, 110, or 220 mcg from the actuator, respectively. The 10.6-g (labeled as containing 44 mcg of fluticasone propionate) or 12-g canister (labeled as containing 110 or 220 mcg of fluticasone propionate) delivers 120 metered sprays of fluticasone propionate.

Each actuation of the oral aerosol inhaler containing the fixed combination of fluticasone propionate and salmeterol xinafoate delivers 50, 125, or 250 mcg of fluticasone propionate and 25 mcg of salmeterol from the valve. Dosages of fluticasone propionate and salmeterol in the fixed-combination inhalation aerosol are expressed in terms of drug delivered from the mouthpiece; each actuation of the inhaler delivers 45, 115, or 230 mcg of fluticasone propionate and 21 mcg of salmeterol from the mouthpiece. The commercially available inhalation aerosol of fluticasone propionate in fixed combination with salmeterol delivers 60 or 120 metered sprays per 8- or 12-g canister, respectively.

With commercially available fluticasone propionate inhalation powder (Flovent(R) Diskus(R), Advair(R) Diskus(R)) delivered via the Diskus(R) device, the amount of drug delivered to the lungs depends on factors such as the patient's inspiratory flow. Using standardized in vitro testing at a flow rate of 60 L per minute for 2 seconds, the Flovent(R) Diskus(R) labeled as containing 50, 100, or 250 mcg of fluticasone propionate delivers 46, 94, or 235 mcg of fluticasone propionate, respectively. In adults with obstructive lung disease and severely compromised lung function (FEV1 20-30% of predicted), mean peak inspiratory flow through the Diskus(R) device was 82.4

L/minute. In children 4 and 8 years of age with asthma, mean peak inspiratory flow through the Diskus(R) device was 70 and 104 L/minute, respectively. Using standardized in vitro testing at a flow rate of 60 L per minute for 2 seconds, the Advair(R) Diskus(R) device delivered 93, 233, and 465 mcg of fluticasone propionate and 45 mcg of salmeterol per activation from a Diskus(R) labeled as containing 100, 250, or 500 mcg of fluticasone propionate and 50 mcg of salmeterol, respectively.

In adults with obstructive lung disease and severely compromised lung function (FEV1 20-30% of predicted), mean peak inspiratory flow through the Diskus(R) device was 82.4 L/minute for Advair(R). In adults and adolescents with asthma, mean peak inspiratory flow through the Diskus(R) device was 122.2

L/minute. In a group of children 4 years of age, mean peak inspiratory flow through the Advair(R) Diskus(R) device averaged 75.5 L/minute; in children 8 years of age, mean peak inspiratory flow averaged 107.3 L/minute.

Fluticasone propionate is administered by nasal inhalation using a metered-dose nasal spray pump. Patients should be instructed carefully in the use of the nasal spray pump, including the need to prime the pump prior to first use or after a period of nonuse (i.e., 1 week or more). To obtain optimum results, patients also should be given a copy of the patient instructions provided by the manufacturer.

Prior to administration of fluticasone propionate nasal spray, patients should clear their nasal passages; administration of a topical nasal decongestant about 5-15 minutes before intranasal corticosteroid administration may be useful during the first 2 or 3 days of therapy in patients with blocked nasal passages to ensure adequate penetration of the drug. Prior to initial use, the nasal inhaler must be primed. Patients should tilt the head slightly forward, insert the nasal adapter into one nostril, and point the tip of the adapter toward the inflamed nasal turbinates and away from the nasal septum.

For maximum therapeutic effect and to ensure adequate penetration of the drug, patients should pump the drug into one nostril while holding the other nostril closed and should concurrently inspire through the nose. This procedure is then repeated for the other nostril. If sneezing occurs during drug administration, patients should wait until sneezing has stopped, then clear the nasal passages and repeat administration of the dose.

The manufacturer recommends cleaning of the nasal spray adapter and/or pump at least once weekly. After removing the nasal adapter and dust cap, these pieces should be rinsed in warm water and dried thoroughly. If the nasal adapter becomes clogged, the piece should be soaked in warm water; cleaning by inserting a sharp object into the piece is not recommended.

Fluticasone propionate alone and in fixed combination with salmeterol is administered as a microcrystalline suspension by oral inhalation using an oral aerosol inhaler with hydrofluoroalkane (HFA; non-chlorofluorocarbon) propellant or as the inhalation powder using the Diskus(R) device that delivers the drug from foil-wrapped blisters. Fluticasone propionate in fixed combination with salmeterol xinafoate is also administered as an inhalation powder using the Diskus(R) device that delivers the drugs from foil-wrapped blisters.

Dosing information for FLUTICASONE PROPIONATE
DRUG LABEL	DOSING TYPE	DOSING INSTRUCTIONS
FLUTICASONE PROP 50 MCG SPRAY	Maintenance	Adults spray 1 - 2 sprays (50 - 100 mcg) in each nostril by intranasal route once daily as needed
FLUTICASONE PROP 0.05% CREAM	Maintenance	Adults apply a thin layer to the affected area(s) by topical route once daily ; rub in gently and completely
FLUTICASONE PROP 50 MCG DISKUS	Maintenance	Adults inhale 2 puffs (100 mcg) by inhalation route 2 times per day

Generic dosing information for FLUTICASONE PROPIONATE
DRUG LABEL	DOSING TYPE	DOSING INSTRUCTIONS
FLUTICASONE PROP 50 MCG SPRAY	Maintenance	Adults spray 1 - 2 sprays (50 - 100 mcg) in each nostril by intranasal routeonce daily as needed
FLUTICASONE PROP 0.05% CREAM	Maintenance	Adults apply a thin layer to the affected area(s) by topical route once daily ; rub in gently and completely
EQL FLUTICASONE PROP 50 MCG SP	Maintenance	Adults spray 1 - 2 sprays (50 - 100 mcg) in each nostril by intranasal routeonce daily as needed
GNP FLUTICASONE PROP 50 MCG SP	Maintenance	Adults spray 1 - 2 sprays (50 - 100 mcg) in each nostril by intranasal routeonce daily as needed
FLUTICASONE PROP 50 MCG DISKUS	Maintenance	Adults inhale 2 puffs (100 mcg) by inhalation route 2 times per day
CVS FLUTICASONE PROP 50 MCG SP	Maintenance	Adults spray 1 - 2 sprays (50 - 100 mcg) in each nostril by intranasal routeonce daily as needed

The following drug interaction information is available for FLUTICASONE PROPIONATE (fluticasone propionate):

Contraindicated
Severe
Moderate

There are 1 contraindications. These drug combinations generally should not be dispensed or administered to the same patient. A manufacturer label warning that indicates the contraindication warrants inclusion of a drug combination in this category, regardless of clinical evidence or lack of clinical evidence to support the contraindication.

Drug Interaction	Drug Names
Desmopressin/Glucocorticoids SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient. MECHANISM OF ACTION: Glucocorticoids increase the risk of hyponatremia.(1-4) CLINICAL EFFECTS: Concurrent use of glucocorticoids may increase the risk of hyponatremia with desmopressin.(1-4) PREDISPOSING FACTORS: Predisposing factors for hyponatremia include: polydipsia, renal impairment (eGFR < 50 ml/min/1.73m2), illnesses that can cause fluid/electrolyte imbalances, age >=65, medications that cause water retention and/or increase the risk of hyponatremia (carbamazepine, chlorpromazine, lamotrigine, loop diuretics, NSAIDs, opioids, SSRIs, thiazide diuretics, and/or tricyclic antidepressants). PATIENT MANAGEMENT: The concurrent use of systemic or inhaled glucocorticoids with desmopressin is contraindicated.(1-4) Desmopressin may be initiated 3 days or 5 half-lives after glucocorticoid discontinuation, whichever is longer. If concurrent use is deemed medically necessary, make sure serum sodium levels are normal before beginning therapy and consider using the desmopressin nasal 0.83 mcg dose. Consider measuring serum sodium levels more frequently than the recommended intervals of: within 7 days of concurrent therapy initiation, one month after concurrent therapy initiation and periodically during treatment. Counsel patients to report symptoms of hyponatremia, which may include: headache, nausea/vomiting, feeling restless, fatigue, drowsiness, dizziness, muscle cramps, changes in mental state (confusion, decreased awareness/alertness), seizures, coma, and trouble breathing. Counsel patients to limit the amount of fluids they drink in the evening and night-time and to stop taking desmopressin if they develop a stomach/intestinal virus with nausea/vomiting or any nose problems (blockage, stuffy/runny nose, drainage).(1) DISCUSSION: In clinical trials of desmopressin for the treatment of nocturia, 4 of 5 patients who developed severe hyponatremia (serum sodium <= 125 mmol/L) were taking systemic or inhaled glucocorticoids. Three of these patients were also taking NSAIDs and one was receiving a thiazide diuretic.(2) Drugs associated with hyponatremia may increase the risk, including loop diuretics, carbamazepine, chlorpromazine, glucocorticoids, lamotrigine, NSAIDs, opioids, SSRIs, thiazide diuretics, and/or tricyclic antidepressants.(1,3-4)	DDAVP, DESMOPRESSIN ACETATE, NOCDURNA

Drug Interaction

Drug Names

Desmopressin/Glucocorticoids

SEVERITY LEVEL: 1-Contraindicated Drug Combination: This drug combination is contraindicated and generally should not be dispensed or administered to the same patient.

MECHANISM OF ACTION: Glucocorticoids increase the risk of hyponatremia.(1-4)

CLINICAL EFFECTS: Concurrent use of glucocorticoids may increase the risk of hyponatremia with desmopressin.(1-4)

PREDISPOSING FACTORS: Predisposing factors for hyponatremia include: polydipsia, renal impairment (eGFR < 50 ml/min/1.73m2), illnesses that can cause fluid/electrolyte imbalances, age >=65, medications that cause water retention and/or increase the risk of hyponatremia (carbamazepine, chlorpromazine, lamotrigine, loop diuretics, NSAIDs, opioids, SSRIs, thiazide diuretics, and/or tricyclic antidepressants).

PATIENT MANAGEMENT: The concurrent use of systemic or inhaled glucocorticoids with desmopressin is contraindicated.(1-4) Desmopressin may be initiated 3 days or 5 half-lives after glucocorticoid discontinuation, whichever is longer. If concurrent use is deemed medically necessary, make sure serum sodium levels are normal before beginning therapy and consider using the desmopressin nasal 0.83

mcg dose. Consider measuring serum sodium levels more frequently than the recommended intervals of: within 7 days of concurrent therapy initiation, one month after concurrent therapy initiation and periodically during treatment. Counsel patients to report symptoms of hyponatremia, which may include: headache, nausea/vomiting, feeling restless, fatigue, drowsiness, dizziness, muscle cramps, changes in mental state (confusion, decreased awareness/alertness), seizures, coma, and trouble breathing. Counsel patients to limit the amount of fluids they drink in the evening and night-time and to stop taking desmopressin if they develop a stomach/intestinal virus with nausea/vomiting or any nose problems (blockage, stuffy/runny nose, drainage).(1)

DISCUSSION: In clinical trials of desmopressin for the treatment of nocturia, 4 of 5 patients who developed severe hyponatremia (serum sodium <= 125 mmol/L) were taking systemic or inhaled glucocorticoids. Three of these patients were also taking NSAIDs and one was receiving a thiazide diuretic.(2) Drugs associated with hyponatremia may increase the risk, including loop diuretics, carbamazepine, chlorpromazine, glucocorticoids, lamotrigine, NSAIDs, opioids, SSRIs, thiazide diuretics, and/or tricyclic antidepressants.(1,3-4)

DDAVP, DESMOPRESSIN ACETATE, NOCDURNA

There are 5 severe interactions. These drug interactions can produce serious consequences in most patients. Actions required for severe interactions include, but are not limited to, discontinuing one or both agents, adjusting dosage, altering administration scheduling, and providing additional patient monitoring. Review the full interaction monograph for more information.

Drug Interaction	Drug Names
Selected Steroids/Antiretroviral CYP3A4 Inhibitors SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Antiretroviral CYP3A4 inhibitors may inhibit the metabolism of corticosteroids metabolized by CYP3A4. Dexamethasone may induce metabolism of agents that are substrates of CYP3A4.(1-13,50) CLINICAL EFFECTS: Concurrent use of antiretroviral CYP3A4 inhibitors may result in increased systemic exposure to and effects from corticosteroids metabolized by CYP3A4, including Cushing's syndrome and adrenal suppression. Concurrent dexamethasone may result in decreased levels and effectiveness of CYP3A4 substrates. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: If possible, avoid concurrent therapy of betamethasone, budesonide, ciclesonide, fluticasone, dexamethasone, methylprednisolone, or triamcinolone with antiretroviral CYP3A4 inhibitors. Alternative corticosteroids that are less affected by CYP3A4 inhibitors should be considered, like beclomethasone, prednisone, and prednisolone. If concurrent therapy is warranted, patients should be closely monitored for systemic effects. The corticosteroid may need to be discontinued. Patients receiving concurrent therapy with dexamethasone and substrates of CYP3A4 should also be monitored for decreased effectiveness of the CYP3A4 substrate. The manufacturers of nasal fluticasone(14-16) and fluticasone for inhalation(17) state that concurrent use of fluticasone and atazanavir, indinavir, nelfinavir, ritonavir or saquinavir is not recommended. The US manufacturers of atazanavir,(1) fosamprenavir,(5) indinavir(6) and nelfinavir(8) recommend caution with concurrent use of inhaled or nasal fluticasone. Consider alternatives to fluticasone if long-term use is required. DISCUSSION: In a study, boceprevir (800 mg TID for 7 days) increased the area-under-curve (AUC) of a single dose of prednisone (40 mg) by 22%. The maximum concentration (Cmax) and AUC of prednisolone increased by 16% and 37%, respectively.(2) A study of 14 healthy adults found that concurrent use of ketoconazole with ciclesonide increased the AUC of ciclesonide's active metabolite, des-ciclesonide, by approximately 3.6-fold at steady state, while levels of ciclesonide remained unchanged. However, the study concluded that no dosage adjustments were required because ciclesonide has a very low potential to cause side effects.(18) A study in 18 healthy subjects examined the effects of ritonavir (100 mg twice daily) on fluticasone nasal spray (200 mcg daily). In most subjects, fluticasone was undetectable (<10 pg/ml) when administered alone. In subjects in whom fluticasone was detectable when given alone, Cmax and area-under-curve AUC averaged 11.9 pg/ml and 8.43 pg x hr/ml, respectively. With concurrent ritonavir, fluticasone Cmax and AUC increased to 318 pg/ml and 3102.6 pg x hr/ml, respectively.(7,11,14) This reflects increases in Cmax and AUC by 25-fold and 350-fold, respectively.(3) The cortisol AUC decreased by 86%.(6,14-16) In a study in 10 healthy subjects, ritonavir (200 mg twice daily for 4 and 14 days) increased the AUC of a single dose of prednisolone by 1.41-fold and 1.30-fold, respectively, after 4 days and 14 days of ritonavir.(19) There have been several case reports of Cushing's syndrome in patients treated concurrently with ritonavir and inhaled budesonide,(19-20) dexamethasone,(22) injectable triamcinolone,(23-26) nasal fluticasone.(28-46) Hepatitis has also been reported with concurrent budesonide and ritonavir.(47) In a study in 9 healthy subjects, mibefradil (50 mg once daily for 3 days) increased the AUC, Cmax, and elimination half-life of methylprednisolone by 3.8-fold, 1.8-fold, and 2.7-fold, respectively.(48) In a study in 8 healthy subjects, following nefazodone administration the following changes were seen with methylprednisolone: mean (+/-SD) area under the concentration-time curve was significantly higher (1393 +/- 343 vs. 2966 +/- 928 ug*h/L; P < 0.005), apparent clearance was lower (28.7 +/- 7.2 vs. 14.6 +/- 7.8 L/h; P < 0.02) and the terminal elimination half-life was longer (2.28 +/- 0.49 vs. 3.32 +/- 0.95 hours; P < 0.02).(49) Selected steroids linked to this monograph include: betamethasone, budesonide, ciclesonide, dexamethasone, fluticasone, methylprednisolone, and triamcinolone.(50) Selected CYP3A4 inhibitors and substrates linked to this monograph include: atazanavir, cobicistat, darunavir, fosamprenavir, indinavir, lenacapavir, lopinavir, nelfinavir, saquinavir, and tipranavir.(50)	APTIVUS, ATAZANAVIR SULFATE, DARUNAVIR, EVOTAZ, FOSAMPRENAVIR CALCIUM, GENVOYA, KALETRA, LOPINAVIR-RITONAVIR, PREZCOBIX, PREZISTA, REYATAZ, STRIBILD, SUNLENCA, SYMTUZA, TYBOST, VIRACEPT
Radioactive Iodide/Agents that Affect Iodide SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Many compounds can affect iodide protein binding and alter iodide pharmacokinetics and pharmacodynamics.(1) CLINICAL EFFECTS: Compounds that affect iodide pharmacokinetics and pharmacodynamics may impact the effectiveness of radioactive iodide.(1) PREDISPOSING FACTORS: Compounds that affect iodide pharmacokinetics and pharmacodynamics are expected to have the most impact during therapy using radioactive iodide. Diagnostic procedures would be expected to be impacted less. PATIENT MANAGEMENT: Discuss the use of agents that affect iodide pharmacokinetics and pharmacodynamics with the patient's oncologist.(1) Because indocyanine green contains sodium iodide, the iodine-binding capacity of thyroid tissue may be reduced for at least one week following administration. Do not perform radioactive iodine uptake studies for at least one week following administration of indocyanine green.(2) The manufacturer of iopamidol states administration may interfere with thyroid uptake of radioactive iodine and decrease therapeutic and diagnostic efficacy. Avoid thyroid therapy or testing for up to 6 weeks post administration of iopamidol.(3) DISCUSSION: Many agents interact with radioactive iodine. The average duration of effect is: anticoagulants - 1 week antihistamines - 1 week anti-thyroid drugs, e.g: carbimazole, methimazole, propylthiouracil - 3-5 days corticosteroids - 1 week iodide-containing medications, e.g: amiodarone - 1-6 months expectorants - 2 weeks Lugol solution - 3 weeks saturated solution of potassium iodine - 3 weeks vitamins - 10-14 days iodide-containing X-ray contrast agents - up to 1 year lithium - 4 weeks phenylbutazone - 1-2 weeks sulfonamides - 1 week thyroid hormones (natural or synthetic), e.g.: thyroxine - 4 weeks tri-iodothyronine - 2 weeks tolbutamide - 1 week topical iodide - 1-9 months (1)	ADREVIEW, JEANATOPE, MEGATOPE, SODIUM IODIDE I-123
Cosyntropin/Agents Affecting Plasma Cortisol Levels SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Agents affecting plasma cortisol levels may impact the accuracy of the cosyntropin diagnostic test.(1) CLINICAL EFFECTS: Concurrent use of agents affecting plasma cortisol levels may impact the accuracy of the cosyntropin diagnostic test.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: The US manufacturer of cosyntropin states accuracy of diagnosis using the cosyntropin diagnostic test may be complicated by concomitant medications affecting plasma cortisol levels.(1) Agents affecting plasma cortisol levels and recommendation to stop prior to cosyntropin diagnostic test include: - Glucocorticoids: May elevate plasma cortisol levels. Stop these drugs on the day of testing. Long-acting glucocorticoids may need to be stopped for a longer period before testing. - Spironolactone: May elevate plasma cortisol levels. Stop spironolactone on the day of testing. - Estrogen: May elevate plasma total cortisol levels. Discontinue estrogen containing drugs 4 to 6 weeks prior to testing to allow cortisol binding globulin levels to return to levels within the reference range. Alternatively, concomitant measurement of cortisol binding globulin at the time of testing can be done; if cortisol binding globulin levels are elevated, plasma total cortisol levels are considered inaccurate.(1) DISCUSSION: Concurrent use of agents affecting plasma cortisol levels may impact the accuracy of the cosyntropin diagnostic test.(1)	CORTROSYN, COSYNTROPIN
Selected Steroids/Selected Strong CYP3A4 Inhibitors SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Strong CYP3A4 inhibitors may inhibit the metabolism of corticosteroids metabolized by CYP3A4. CLINICAL EFFECTS: Concurrent use of strong CYP3A4 inhibitors may result in increased systemic exposure to and effects from corticosteroids metabolized by CYP3A4, including Cushing's syndrome and adrenal suppression. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: If possible, avoid concurrent therapy between betamethasone, budesonide, ciclesonide, fluticasone, dexamethasone, methylprednisolone, or triamcinolone and strong CYP3A4 inhibitors. Alternative corticosteroids that are less affected by CYP3A4 inhibitors should be considered, like beclomethasone, prednisone, and prednisolone. If concurrent therapy is warranted, patients should be closely monitored for systemic effects. The corticosteroid may need to be discontinued. DISCUSSION: In a study, boceprevir (800 mg TID for 7 days) increased the area-under-curve (AUC) of a single dose of prednisone (40 mg) by 22%. The maximum concentration (Cmax) and AUC of prednisolone increased by 16% and 37%, respectively.(3) A study of 14 healthy adults found that concurrent use of ketoconazole with ciclesonide increased the AUC of ciclesonide's active metabolite, des-ciclesonide, by approximately 3.6-fold at steady state, while levels of ciclesonide remained unchanged. However, the study concluded that no dosage adjustments were required because ciclesonide has a very low potential to cause side effects.(4) A study in 18 healthy subjects examined the effects of ritonavir (100 mg twice daily) on fluticasone nasal spray (200 mcg daily). In most subjects, fluticasone was undetectable (<10 pg/ml) when administered alone. In subjects in whom fluticasone was detectable when given alone, Cmax and area-under-curve AUC averaged 11.9 pg/ml and 8.43 pg x hr/ml, respectively. With concurrent ritonavir, fluticasone Cmax and AUC increased to 318 pg/ml and 3102.6 pg x hr/ml, respectively.(6-8) This reflects increases in Cmax and AUC by 25-fold and 350-fold, respectively.(6) The cortisol AUC decreased by 86%.(10-13) In a study in 10 healthy subjects, ritonavir (200 mg twice daily for 4 and 14 days) increased the AUC of a single dose of prednisolone by 1.41-fold and 1.30-fold, respectively, after 4 days and 14 days of ritonavir.(14) There have been several case reports of Cushing's syndrome in patients treated concurrently with ritonavir and inhaled budesonide,(15-16) dexamethasone,(17) injectable triamcinolone,(18-21) nasal fluticasone.(23-41) Hepatitis has also been reported with concurrent budesonide and ritonavir.(42) In a study in 9 healthy subjects, mibefradil (50 mg once daily for 3 days) increased the AUC, Cmax, and elimination half-life of methylprednisolone by 3.8-fold, 1.8-fold, and 2.7-fold, respectively.(43) In a study in 8 healthy subjects, following nefazodone administration the following changes were seen with methylprednisolone: mean (+/-SD) area under the concentration-time curve was significantly higher (1393 +/- 343 vs. 2966 +/- 928 ug*h/L; P < 0.005), apparent clearance was lower (28.7 +/- 7.2 vs. 14.6 +/- 7.8 L/h; P < 0.02) and the terminal elimination half-life was longer (2.28 +/- 0.49 vs. 3.32 +/- 0.95 hours; P < 0.02).(44) Selected steroids linked to this monograph include: betamethasone, budesonide, ciclesonide, dexamethasone, fluticasone, methylprednisolone, and triamcinolone.(45) Selected CYP3A4 inhibitors linked to this monograph include: adagrasib, boceprevir, ceritinib, lonafarnib, mibefradil, nefazodone, ribociclib, paritaprevir, telaprevir, and tucatinib.(1-2,45)	KISQALI, KRAZATI, NEFAZODONE HCL, TUKYSA, ZOKINVY, ZYKADIA
Sodium Iodide I 131/Agents that Affect Iodide SEVERITY LEVEL: 2-Severe Interaction: Action is required to reduce the risk of severe adverse interaction. MECHANISM OF ACTION: Many compounds can affect iodide protein binding and alter iodide pharmacokinetics and pharmacodynamics.(1,2) CLINICAL EFFECTS: Compounds that affect iodide pharmacokinetics and pharmacodynamics may impact the effectiveness of radioactive iodide.(1,2) PREDISPOSING FACTORS: Compounds that affect iodide pharmacokinetics and pharmacodynamics are expected to have the most impact during therapy using radioactive iodide. Diagnostic procedures would be expected to be impacted less. PATIENT MANAGEMENT: Discuss the use of agents that affect iodide pharmacokinetics and pharmacodynamics with the patient's oncologist.(1,2) Because indocyanine green contains sodium iodide, the iodine-binding capacity of thyroid tissue may be reduced for at least one week following administration. Do not perform radioactive iodine uptake studies for at least one week following administration of indocyanine green.(3) The manufacturer of iopamidol states administration may interfere with thyroid uptake of radioactive iodine and decrease therapeutic and diagnostic efficacy. Avoid thyroid therapy or testing for up to 6 weeks post administration of iopamidol.(4) DISCUSSION: Many agents interact with radioactive iodine. The average duration of effect is: anticoagulants - 1 week antihistamines - 1 week anti-thyroid drugs, e.g: carbimazole, methimazole, propylthiouracil - 3-5 days corticosteroids - 1 week iodide-containing medications, e.g: amiodarone - 1-6 months expectorants - 2 weeks Lugol solution - 3 weeks saturated solution of potassium iodine - 3 weeks vitamins - 10-14 days iodide-containing X-ray contrast agents - up to 1 year lithium - 4 weeks phenylbutazone - 1-2 weeks sulfonamides - 1 week thyroid hormones (natural or synthetic), e.g.: thyroxine - 4 weeks tri-iodothyronine - 2 weeks tolbutamide - 1 week topical iodide - 1-9 months (1,2)	HICON, SODIUM IODIDE I-131

There are 5 moderate interactions. The clinician should assess the patient’s characteristics and take action as needed. Actions required for moderate interactions include, but are not limited to, discontinuing one or both agents, adjusting dosage, altering administration.

Drug Interaction	Drug Names
Corticosteroids/Selected Macrolide Antibiotics SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Some macrolide antibiotics may inhibit the metabolism of corticosteroids. CLINICAL EFFECTS: Concurrent use of some macrolide antibiotics may result in elevated levels and clinical effects of corticosteroids. Immunosuppression and Cushing's syndrome have been reported during concurrent therapy, including therapy with inhaled corticosteroids. PREDISPOSING FACTORS: Concurrent administration of enzyme inducing drugs. PATIENT MANAGEMENT: Patients receiving concurrent therapy with corticosteroids and macrolide antibiotics should be monitored for increased corticosteroid affects. The dosage of the corticosteroid may need to be adjusted or the macrolide antibiotic may need to be discontinued. One US manufacturer of inhaled fluticasone states that the concurrent use of macrolide antibiotics is not recommended.(1) DISCUSSION: In a study in 10 steroid-dependent asthmatics, concurrent troleandomycin (1 gram/day) decreased methylprednisolone clearance by 60%. All subjects developed adverse effects typical of excessive corticosteroid use such as weight gain, fluid retention, and cushingoid features.(2) Other studies and reports have shown increased methylprednisolone levels with concurrent troleandomycin,(3-10) in some of these reports, the interaction was used to lower steroid dosages.(6-10) There is one report of fatal varicella infection in a patient receiving concurrent therapy with methylprednisolone and troleandomycin.(11) Cushing's syndrome has been reported with concurrent inhaled budesonide and clarithromycin.(12) Psychosis(13) and mania(14) have been reported with concurrent prednisone and clarithromycin. Erythromycin(3-9) and troleandomycin(9) have also been reported to interact with methylprednisolone.	CLARITHROMYCIN, CLARITHROMYCIN ER, E.E.S. 200, E.E.S. 400, ERY-TAB, ERYPED 200, ERYPED 400, ERYTHROCIN LACTOBIONATE, ERYTHROCIN STEARATE, ERYTHROMYCIN, ERYTHROMYCIN ESTOLATE, ERYTHROMYCIN ETHYLSUCCINATE, ERYTHROMYCIN LACTOBIONATE, LANSOPRAZOL-AMOXICIL-CLARITHRO, OMECLAMOX-PAK, VOQUEZNA TRIPLE PAK
Quinolones/Corticosteroids SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Quinolone-induced arthropathy is a class effect of the quinolones.(1) Exactly how corticosteroid use increases the risk of tendon rupture is unknown. CLINICAL EFFECTS: Concurrent use of quinolones and corticosteroids may increase the risk of tendonitis and/or tendon rupture. This affect is most common in the Achilles tendon, but has been reported in the rotator cuff (shoulder), hand, biceps, thumb, and other tendons.(2-9) PREDISPOSING FACTORS: Risk factors for tendinitis and tendon rupture include age greater than 60; a history of kidney, heart, or lung transplantation, strenuous physical activity, renal failure, and previous tendon disorders such as rheumatoid arthritis. PATIENT MANAGEMENT: Quinolone use should be discontinued if the patient experiences pain, inflammation, or rupture of a tendon. Patients should be instructed to rest and refrain from exercise until the diagnosis of tendonitis tendon rupture has been excluded.(2-9) DISCUSSION: Ruptures of the shoulder, hand, Achilles tendon, or other tendons that required surgical repair or resulted in prolonged disability have been reported in patients receiving ciprofloxacin,(2) gatifloxacin,(3) levofloxacin,(4) lomefloxacin,(5) moxifloxacin,(6) nalidixic acid,(7) norfloxacin,(8) and ofloxacin.(9) A retrospective review of the IMS Health database examined quinolone use use from July 1, 1992 to June 30, 1998. The adjusted relative risk of tendon disorder with concurrent quinolone use was 1.9. Relative risk increased to 3.2 in patients aged 60 or older compared to 0.9 in patients aged less than 60. In patients aged 60 or older who used corticosteroids and quinolones concurrently, relative risk increased to 6.2.(10) In contrast, another retrospective review examined patients from a health insurance claims database and found no apparent effect from concurrent quinolone and corticosteroid use.(11) In a review of the follow-up to 42 spontaneously reported case of quinolone-associated tendon disorders in the Netherlands between January, 1988 and January, 1998, risk factors for tendon disorders included age older than 60, oral corticosteroid use, and existing joint problems.(12) In a review of the Swiss Drug Monitoring system, four of seven cases of levofloxacin-associated tendon problems also involved concurrent oral or inhaled corticosteroids.(13) In a review of the Medline database from 1966-2001, 98 case reports of tendinopathy associated with quinolones were located. Thirty-two (32.7%) of the patients had received systemic or inhaled corticosteroids before and during quinolone therapy. Of the 40 patients who suffered a tendon rupture, 21 (52.5%) were receiving corticosteroids.(14) Other authors have reported cases of tendon disorders in patients receiving concurrent corticosteroids and ciprofloxacin,(15) levofloxacin, (16-20) and ofloxacin.(21)	AVELOX IV, BAXDELA, CIPRO, CIPROFLOXACIN, CIPROFLOXACIN HCL, CIPROFLOXACIN-D5W, GATIFLOXACIN SESQUIHYDRATE, LEVOFLOXACIN, LEVOFLOXACIN HEMIHYDRATE, LEVOFLOXACIN-D5W, MOXIFLOXACIN, MOXIFLOXACIN HCL, NALIDIXIC ACID, OFLOXACIN
Selected Corticosteroids/Selected Azole Antifungal Agents SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Itraconazole, ketoconazole, posaconazole, and voriconazole may inhibit the CYP3A4 mediated metabolism of some corticosteroids, resulting in increased systemic exposure. Itraconazole and ketoconazole may also suppress endogenous cortisol output. CLINICAL EFFECTS: Concurrent use of itraconazole, ketoconazole, posaconazole, or voriconazole may result in elevated levels of and effects from the corticosteroid, including Cushing syndrome. These effects have been seen with systemic as well as inhaled corticosteroids. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Patients should be carefully monitored with concurrent administration of these agents, or when itraconazole, ketoconazole, posaconazole, or voriconazole is added to corticosteroid therapy. The dose of the corticosteroid may need to be adjusted or alternative therapy considered. DISCUSSION: In a randomized, double-blind, cross-over study in 10 healthy subjects, pretreatment with itraconazole (200 mg daily for 5 days) increased the area-under-curve (AUC) and maximum concentration (Cmax) of a single inhaled dose of budesonide (1000 mcg) by 4.2-fold and 1.6-fold, respectively. Suppression of cortisol production was increased 43%.(1) A study examined adrenal insufficiency in 25 cystic fibrosis patients treated with itraconazole and inhaled budesonide and in 12 patients receiving itraconazole alone. Eleven of the 25 patients receiving concurrent itraconazole and budesonide and none of the patients receiving only itraconazole had adrenal insufficiency.(2) There are case reports of Cushing syndrome in patients receiving concurrent itraconazole (range 200 mg to 800 mg daily) and inhaled budesonide (range 400 mcg to 1400 mcg daily).(3-5) The concurrent use of ketoconazole has been shown to increase budesonide area-under-curve (AUC) by eight-fold.(6) In a study in eight healthy subjects, the simultaneous administration of ketoconazole increased budesonide AUC by 6.5-fold. Administering the two agents 12 hours apart increased budesonide AUC by 3.8-fold.(7) There are case reports of Cushing syndrome in patients receiving concurrent itraconazole (range 100 mg to 400 mg daily) and inhaled fluticasone (range 250 mcg to 1.5 mg daily).(8,9) In a randomized, placebo-controlled, crossover, four phase study in 8 healthy subjects, itraconazole decreased the systemic clearance of intravenous dexamethasone by 68%, increased the area-under-curve (AUC) of dexamethasone by 3.3-fold, and prolonged its half-life by 3.2-fold. The AUC of oral dexamethasone was increased 3.7-fold, maximum concentration (Cmax) was increased by 1.7-fold, and the elimination half-life was prolonged 2.8-fold by itraconazole.(10) In a randomized, cross-over study in 14 healthy subjects, pretreatment with itraconazole (400 mg Day 1, 200 mg Days 2-4) increased the AUC of a single oral dose of methylprednisolone by 1.5-fold. Cortisol levels were significantly lower after concurrent therapy than with methylprednisolone alone.(11) There is a case report of Cushing syndrome following the addition of itraconazole (400 mg daily) to methylprednisolone (12 mg/day).(12) In a study in 6 healthy subjects, pretreatment with ketoconazole (200 mg daily) increased the AUC of a single intravenous dose of methylprednisolone (20 mg) by 135% and decreased its clearance by 60%. Concurrent ketoconazole also increased the reduction in 24-hour cortisol AUC and suppressed morning cortisol concentrations.(13) In a study in 8 healthy subjects, ketoconazole decreased the clearance of methylprednisolone by 46% and increased mean residence time by 37%.(14) In a randomized, cross-over study in 14 healthy subjects, pretreatment with itraconazole (400 mg Day 1, 200 mg Days 2-4) had no effect on the pharmacokinetics of a single oral dose of prednisone (60 mg).(11) In a randomized, cross-over study in 6 healthy subjects, pretreatment with ketoconazole (200 mg daily for 6 days) had no effect on the pharmacokinetics of a single intravenous dose of prednisolone (14.8 mg).(15) In a randomized, double-blind, cross-over study in 10 healthy subjects, pretreatment with itraconazole (200 mg daily for 4 days) increased the AUC and half-life of a single oral dose of prednisolone (20 mg) by 24% and 29%, respectively.(16) In a study, concurrent oral ketoconazole increased the AUC of des-ciclesonide from orally inhaled ciclesonide by 3.6-fold. There were no changes in ciclesonide levels.(17) In a study in 24 healthy subjects, subjects were randomized to receive either ketoconazole (200 mg BID) or placebo on Days 4-9 of a a 9 day course of mometasone (400 mcg BID). No subject had mometasone levels greater than 150 pcg/ml on Day 3. Four of 12 subjects who received ketoconazole had mometasone Cmax levels greater than 200 mcg/ml on Day 9. Plasma cortisol levels appeared to decrease as well.(18) In a cross-over study in 15 healthy subjects, subjects were randomized to receive fluticasone furoate and vilanterol on days 5-11 with either ketoconazole (200mg once daily) or placebo for days 1-11 with a washout period of 7-14 days. Fluticasone furoate AUC was increased by 36%, Cmax was increased by 33%, and decreased systemic cortisol levels by 27%. There were no effects on heart rate and blood potassium levels. There was a small increase in QTc which was 7.6ms greater when compared to placebo; however, ketoconazole has been reported to increase QTc by 5-6ms. Vilanterol AUC was increased by 65% and Cmax was increased by 22%. There were no effects on heart rate and blood potassium levels. No serious adverse events occurred and no subjects withdrew from the study due to adverse events. The most common adverse event reported was headache. (19) Coadministration of orally inhaled fluticasone (1000 mcg) and ketoconazole (200 mg once daily) resulted in a 1.9-fold increase in plasma fluticasone exposure and a 45% decrease in plasma cortisol AUC.(20) There is a case report of Cushing syndrome following the addition of voriconazole (200 mg twice daily for 21 days for 2 courses) to budesonide,(21) as well as voriconazole added to intranasal mometasone(22) and inhaled fluticasone.(22) There is a case report of Cushing syndrome following the addition of posaconazole (200 mg three times daily) to inhaled fluticasone.(23)	ITRACONAZOLE, ITRACONAZOLE MICRONIZED, KETOCONAZOLE, NOXAFIL, POSACONAZOLE, SPORANOX, TOLSURA, VFEND, VFEND IV, VORICONAZOLE
Selected Corticosteroids/Levoketoconazole SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Levoketoconazole may inhibit the CYP3A4 mediated metabolism of some corticosteroids, resulting in increased systemic exposure. Levoketoconazole may also suppress endogenous cortisol output. Levoketoconazole is the enantiomer of ketoconazole. CLINICAL EFFECTS: Concurrent use of levoketoconazole may result in elevated levels of and effects from the corticosteroid, including Cushing syndrome. These effects have been seen with systemic as well as inhaled corticosteroids. PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Patients should be carefully monitored with concurrent administration of these agents, or when levoketoconazole is added to corticosteroid therapy. The dose of the corticosteroid may need to be adjusted or alternative therapy considered. DISCUSSION: The concurrent use of ketoconazole has been shown to increase budesonide area-under-curve (AUC) by eight-fold. In a study in eight healthy subjects, the simultaneous administration of ketoconazole increased budesonide AUC by 6.5-fold. Administering the two agents 12 hours apart increased budesonide AUC by 3.8-fold. In a study in 6 healthy subjects, pretreatment with ketoconazole (200 mg daily) increased the AUC of a single intravenous dose of methylprednisolone (20 mg) by 135% and decreased its clearance by 60%. Concurrent ketoconazole also increased the reduction in 24-hour cortisol AUC and suppressed morning cortisol concentrations. In a study in 8 healthy subjects, ketoconazole decreased the clearance of methylprednisolone by 46% and increased mean residence time by 37%. In a randomized, cross-over study in 6 healthy subjects, pretreatment with ketoconazole (200 mg daily for 6 days) had no effect on the pharmacokinetics of a single intravenous dose of prednisolone (14.8 mg). In a study, concurrent oral ketoconazole increased the AUC of des-ciclesonide from orally inhaled ciclesonide by 3.6-fold. There were no changes in ciclesonide levels. In a study in 24 healthy subjects, subjects were randomized to receive either ketoconazole (200 mg BID) or placebo on Days 4-9 of a a 9 day course of mometasone (400 mcg BID). No subject had mometasone levels greater than 150 pcg/ml on Day 3. Four of 12 subjects who received ketoconazole had mometasone Cmax levels greater than 200 mcg/ml on Day 9. Plasma cortisol levels appeared to decrease as well. In a cross-over study in 15 healthy subjects, subjects were randomized to receive fluticasone furoate and vilanterol on days 5-11 with either ketoconazole (200mg once daily) or placebo for days 1-11 with a washout period of 7-14 days. Fluticasone furoate AUC was increased by 36%, Cmax was increased by 33%, and decreased systemic cortisol levels by 27%. There were no effects on heart rate and blood potassium levels. There was a small increase in QTc which was 7.6ms greater when compared to placebo; however, ketoconazole has been reported to increase QTc by 5-6ms. Vilanterol AUC was increased by 65% and Cmax was increased by 22%. There were no effects on heart rate and blood potassium levels. No serious adverse events occurred and no subjects withdrew from the study due to adverse events. The most common adverse event reported was headache. Coadministration of orally inhaled fluticasone (1000 mcg) and ketoconazole (200 mg once daily) resulted in a 1.9-fold increase in plasma fluticasone exposure and a 45% decrease in plasma cortisol AUC.	RECORLEV
Selected Steroids/Nirmatrelvir-Ritonavir SEVERITY LEVEL: 3-Moderate Interaction: Assess the risk to the patient and take action as needed. MECHANISM OF ACTION: Nirmatrelvir/ritonavir may inhibit the metabolism of corticosteroids metabolized by CYP3A4.(1) CLINICAL EFFECTS: Nirmatrelvir/ritonavir may result in increased systemic exposure to and effects from corticosteroids metabolized by CYP3A4.(1) PREDISPOSING FACTORS: None determined. PATIENT MANAGEMENT: Coadministration with corticosteroids of all routes of administration of which exposures are significantly increased by strong CYP3A4 inhibitors can increase the risk of Cushing's syndrome and adrenal suppression. However, the risk of Cushing's syndrome and adrenal suppression associated with short-term use of a strong CYP3A4 inhibitor is low.(1) The manufacturer of nirmatrelvir/ritonavir recommends considering alternative corticosteroids including beclomethasone, prednisone, and prednisolone.(1) DISCUSSION: Concurrent use of a single dose of midazolam 2 mg, a CYP3A4 substrate, with nirmatrelvir-ritonavir (300 mg/100 mg twice daily for nine doses) increased the maximum concentration (Cmax) and area-under-curve (AUC) of midazolam by 37% and 143%, respectively.(1) A study in 18 healthy subjects examined the effects of ritonavir (100 mg twice daily) on fluticasone nasal spray (200 mcg daily). In most subjects, fluticasone was undetectable (<10 pg/ml) when administered alone. In subjects in whom fluticasone was detectable when given alone, Cmax and area-under-curve AUC averaged 11.9 pg/ml and 8.43 pg x hr/ml, respectively. With concurrent ritonavir, fluticasone Cmax and AUC increased to 318 pg/ml and 3102.6 pg x hr/ml, respectively.(7,11,13) This reflects increases in Cmax and AUC by 25-fold and 350-fold, respectively.(3) The cortisol AUC decreased by 86%.(3-6) In a study in 10 healthy subjects, ritonavir (200 mg twice daily for 4 and 14 days) increased the AUC of a single dose of prednisolone by 1.41-fold and 1.30-fold, respectively, after 4 days and 14 days of ritonavir.(7) Selected steroids linked to this monograph include: budesonide, ciclesonide, dexamethasone, fluticasone, methylprednisolone, and triamcinolone.(8)	PAXLOVID

The following contraindication information is available for FLUTICASONE PROPIONATE (fluticasone propionate):

Overview
Contraindicated
Severe
Moderate

Drug contraindication overview.

Primary treatment of severe acute asthmatic attacks or status asthmaticus when intensive measures (e.g., oxygen, parenteral bronchodilators, IV corticosteroids) are required. Fluticasone propionate in fixed combination with salmeterol is contraindicated as primary treatment of status asthmaticus or other acute episodes of asthma or chronic obstructive pulmonary disease (COPD) when intensive measures are required. Known hypersensitivity to fluticasone propionate or any ingredient (e.g., milk protein) in the formulation. When fluticasone propionate is used in fixed combination with salmeterol, contraindications associated with salmeterol should be considered.

There are 0 contraindications.

There are 10 severe contraindications. Adequate patient monitoring is recommended for safer drug use.

Severe List
Active tuberculosis
Nasal septal perforation
Nasal septal ulcers
Nasal trauma
Ocular herpes simplex
Ocular hypertension
Open angle glaucoma
Operation on nose
Parasitic infection
Severe infection

There are 10 moderate contraindications. Clinically significant contraindication, where the condition can be managed or treated before the drug may be given safely.

Moderate List
Adrenocortical insufficiency
Cataracts
Epistaxis
Hypothalamic-pituitary insufficiency
Inactive tuberculosis
Open angle glaucoma
Oral candidiasis
Osteopenia
Osteoporosis
Parasitic infection

The following adverse reaction information is available for FLUTICASONE PROPIONATE (fluticasone propionate):

Overview
Severe
Less Severe

Adverse reaction overview.

Adverse effects occurring in more than 3% of patients older than 12 years of age receiving fluticasone propionate HFA oral inhalation aerosol in controlled clinical trials include upper respiratory tract infection, headache, throat irritation, upper respiratory inflammation, sinusitis/sinus infection, candidiasis (including oral candidiasis), cough, hoarseness/dysphonia, and bronchitis. Adverse effects reported in clinical trials with fluticasone propionate HFA inhalation aerosol in pediatric patients (4-11 years of age) generally were similar to those observed in adolescents and adults. Adverse effects occurring in more than 3% of patients receiving fluticasone propionate oral inhalation powder in controlled clinical trials include upper respiratory tract infection, throat irritation, sinusitis/sinus infection, upper respiratory inflammation, rhinitis, viral respiratory infection, cough, bronchitis, oral candidiasis, nausea and vomiting, GI discomfort and pain, viral GI infection, musculoskeletal pain, muscle injury, headache, fever, and viral infection.

There are 38 severe adverse reactions.

More Frequent	Less Frequent
None.	Bronchitis Folliculitis Lesion of nasal mucosa Purpura Skin and skin structure infection Skin atrophy Urticaria

Rare/Very Rare
Adrenocortical insufficiency Anaphylaxis Angioedema Bullous dermatitis Cataracts Central serous chorioretinopathy Contact dermatitis Esophageal candidiasis Glaucoma Hypercortisolism Hyperglycemia Hypersensitivity angiitis Hypothalamic-pituitary insufficiency Immunosuppression Impaired wound healing Influenza Nasal candidiasis Nasal septal perforation Ocular hypertension Ocular pain Osteopenia Osteoporosis Paradoxical bronchospasm Pharyngeal candidiasis Pneumonia Skin and skin structure infection Skin hypopigmentation Skin rash Skin striae Skin ulcer Urticaria

Rare/Very Rare

Adrenocortical insufficiency
Anaphylaxis
Angioedema
Bullous dermatitis
Cataracts
Central serous chorioretinopathy
Contact dermatitis
Esophageal candidiasis
Glaucoma
Hypercortisolism
Hyperglycemia
Hypersensitivity angiitis
Hypothalamic-pituitary insufficiency
Immunosuppression
Impaired wound healing
Influenza
Nasal candidiasis
Nasal septal perforation
Ocular hypertension
Ocular pain
Osteopenia
Osteoporosis
Paradoxical bronchospasm
Pharyngeal candidiasis
Pneumonia
Skin and skin structure infection
Skin hypopigmentation
Skin rash
Skin striae
Skin ulcer
Urticaria

There are 94 less severe adverse reactions.

More Frequent	Less Frequent
Bronchitis Cough Dry nose Epistaxis Erythema Headache disorder Myalgia Nasal passage irritation Oral candidiasis Pharyngeal candidiasis Pharyngitis Sinusitis Stinging of skin Upper respiratory infection	Acute abdominal pain Acute pain at drug application site Back pain Blurred vision Cough Crusted nasal mucosa Dizziness Dysgeusia Erythema of nasal mucosa Fever Headache disorder Nasal congestion Nasal pain Pain in oropharynx Paresthesia Pruritus of skin Rhinorrhea Sinusitis Skin rash Sore throat Telangiectasia Treatment site sequelae Voice change Xerostomia

Rare/Very Rare
Acneiform eruption Aggressive behavior Agitation Alopecia Arthralgia Blistering skin Blurred vision Bruising Contact dermatitis Dental caries Dental discoloration Depression Diarrhea Dizziness Drowsy Dry skin Dyschromia Dyspepsia Dyspnea Ecchymosis Eosinophilia Facial edema Fatigue Fever Flu-like symptoms Glycosuria Hirsutism Hypercortisolism Hyperesthesia Hyperglycemia Hyperkinesis Hypertension Insomnia Irritability Laryngitis Miliaria Muscle rigidity Musculoskeletal pain Nausea Pain in oropharynx Perioral dermatitis Pruritus of skin Rhinitis Rhinorrhea Skin irritation Sleep disorder Sore throat Symptoms of anxiety Thrombophlebitis Toothache Urinary tract infection Viral infection Voice change Vomiting Weight gain Xerostomia

Rare/Very Rare

Acneiform eruption
Aggressive behavior
Agitation
Alopecia
Arthralgia
Blistering skin
Blurred vision
Bruising
Contact dermatitis
Dental caries
Dental discoloration
Depression
Diarrhea
Dizziness
Drowsy
Dry skin
Dyschromia
Dyspepsia
Dyspnea
Ecchymosis
Eosinophilia
Facial edema
Fatigue
Fever
Flu-like symptoms
Glycosuria
Hirsutism
Hypercortisolism
Hyperesthesia
Hyperglycemia
Hyperkinesis
Hypertension
Insomnia
Irritability
Laryngitis
Miliaria
Muscle rigidity
Musculoskeletal pain
Nausea
Pain in oropharynx
Perioral dermatitis
Pruritus of skin
Rhinitis
Rhinorrhea
Skin irritation
Sleep disorder
Sore throat
Symptoms of anxiety
Thrombophlebitis
Toothache
Urinary tract infection
Viral infection
Voice change
Vomiting
Weight gain
Xerostomia

The following precautions are available for FLUTICASONE PROPIONATE (fluticasone propionate):

Pediatric
Pregnant
Lactation
Geriatric

Safety and efficacy of fluticasone propionate inhalation aerosol or powder alone in children younger than 4 years of age have not been established. Safety and efficacy of the inhalation powder containing fluticasone propionate in fixed combination with salmeterol (Advair(R) Diskus(R)) in children younger than 4 years of age have not been established. Safety and efficacy of the inhalation aerosol containing fluticasone propionate in fixed combination with salmeterol (Advair(R) HFA) in children younger than 12 years of age have not been established.

Use of the inhalation powder containing fluticasone propionate in children 4-11 years of age is supported by data from several clinical trials. Use of fluticasone propionate inhalation aerosol or the inhalation powder containing fluticasone propionate in fixed combination with salmeterol (Advair(R) Diskus(R)) in children 4-11 years of age is supported by data from several clinical trials and by extrapolation of efficacy data from older patients. The adverse effect profile of Flovent(R) HFA in pediatric patients (4-11 years of age) generally is similar to that observed in adolescents and adults.

Use of corticosteroids or inadequate control of chronic diseases (e.g., asthma) may lead to suppression of growth in children and adolescents. Therefore, children receiving prolonged therapy with orally inhaled fluticasone propionate should be monitored periodically (e.g., via stadiometry) for possible adverse effects on growth and development. The benefits of corticosteroid therapy should be weighed against the possibility of growth suppression and the risks associated with alternative therapies. Children should be maintained on the lowest possible dosage of fluticasone propionate that controls asthma symptoms.

Contraindicated

None

Severe Precaution

None

Management or Monitoring Precaution

None

Fluticasone propionate nasal spray should be used during pregnancy only when the potential benefits justify the possible risks to the fetus. Since adrenal insufficiency may occur in neonates born to women who received corticosteroids during pregnancy, these neonates should be monitored carefully for manifestations of this condition. Although there are no adequate and well-controlled studies to date using fluticasone propionate in pregnant women, fluticasone propionate has been shown to be teratogenic and embryotoxic in mice or rats when administered subcutaneously at daily dosages of 45 or 100 mcg/kg, respectively (approximately equivalent to 4 times the maximum recommended daily intranasal dosage in adults based on surface area).

Observed fetal toxicity was characteristic of potent glucocorticoid compounds and included embryonic growth retardation, omphalocele, cleft palate, and retarded cranial ossification. Fetal weight reduction and cleft palate were observed in offspring of rabbits given fluticasone propionate 4 mcg/kg subcutaneously (less than the maximum recommended daily intranasal dosage in adults). Following oral administration of up to 300 mcg/kg (approximately 25 times the maximum recommended daily intranasal dosage in adults on a mcg/m2 basis) daily of fluticasone propionate in rabbits, the drug was not detected in plasma, and no maternal effects nor increased incidence of external, visceral, or skeletal fetal defects was detected.

The low bioavailability and small distribution of fluticasone propionate across the placenta may account for the lack of teratogenicity; in rats and rabbits receiving oral fluticasone propionate dosages of 100 mcg/kg (590 mcg/m2) or 300 mcg/kg (3.6 mg/m2), respectively, less than 0.008% of the dose crossed the placenta. Long-term experience with the use of oral glucocorticoids suggests that rodents are more prone to teratogenic effects of glucocorticoids than humans.

In addition, because there is a natural increase in glucocorticoid production during pregnancy, most women will require a lower exogenous glucocorticoid dose and many will not need glucocorticoid treatment during pregnancy. Category C.

Fluticasone propionate should be used with caution in nursing women, since it is not known whether the drug is distributed into milk in humans. Subcutaneous administration of tritiated fluticasone propionate to lactating rats (10 mcg/kg, less than the maximum recommended daily intranasal dosage in adults on a mcg/m2 basis) resulted in measurable radioactivity in both plasma and milk. Other corticosteroids are distributed into milk and in systemic amounts may cause adverse effects, such as growth suppression, in nursing infants.

While it is not known whether fluticasone propionate is distributed into milk in humans, the drug is distributed into milk in rats. In addition, other corticosteroids are distributed into milk. Data also are not available on the effects of the drug on the breast-fed child or on milk production.

Since data are not available on the use of fluticasone propionate oral inhalation aerosol in nursing women, caution is advised if the drug is administered in nursing women. The benefits of breast-feeding should be considered along with the woman's clinical need for fluticasone propionate oral inhalation and any potential adverse effects on the breast-fed child from the drug or underlying maternal condition.

Although no overall differences in safety and efficacy of orally inhaled fluticasone propionate alone or fluticasone propionate in fixed combination with salmeterol as the inhalation aerosol (Advair(R) HFA) were observed relative to younger adults, the possibility that some older patients may exhibit increased sensitivity to the drug cannot be ruled out. Experience with the inhalation powder containing fluticasone propionate in fixed combination with salmeterol (Advair(R) Diskus(R)) in those 65 years of age or older with asthma is insufficient to determine whether geriatric patients respond differently than younger patients. In clinical studies evaluating the inhalation powder containing fluticasone propionate in fixed combination with salmeterol for COPD, patients 65 years of age or older experienced a higher incidence of serious adverse effects compared with those younger than 65 years of age, although the distribution of adverse effects was similar in the two groups.

Dosage of fluticasone propionate HFA inhalation aerosol in geriatric patients should be selected with caution, reflecting the greater frequency of decreased hepatic function, presence of coexisting conditions, or other drug therapies in such patients. Dosage adjustments based solely on age are not recommended in geriatric patients receiving fluticasone propionate inhalation powder alone or fluticasone propionate inhalation powder or aerosol in fixed combination with salmeterol.

The following icd codes are available for FLUTICASONE PROPIONATE (fluticasone propionate)'s list of indications:

Allergic conjunctivitis
H10.1	Acute atopic conjunctivitis
H10.10	Acute atopic conjunctivitis, unspecified eye
H10.11	Acute atopic conjunctivitis, right eye
H10.12	Acute atopic conjunctivitis, left eye
H10.13	Acute atopic conjunctivitis, bilateral
H10.44	Vernal conjunctivitis
H10.45	Other chronic allergic conjunctivitis
H16.26	Vernal keratoconjunctivitis, with limbar and corneal involvement
H16.261	Vernal keratoconjunctivitis, with limbar and corneal involvement, right eye
H16.262	Vernal keratoconjunctivitis, with limbar and corneal involvement, left eye
H16.263	Vernal keratoconjunctivitis, with limbar and corneal involvement, bilateral
H16.269	Vernal keratoconjunctivitis, with limbar and corneal involvement, unspecified eye
Allergic dermatitis
L20	Atopic dermatitis
L20.0	Besnier's prurigo
L20.8	Other atopic dermatitis
L20.81	Atopic neurodermatitis
L20.82	Flexural eczema
L20.83	Infantile (acute) (chronic) eczema
L20.84	Intrinsic (allergic) eczema
L20.89	Other atopic dermatitis
L20.9	Atopic dermatitis, unspecified
L23	Allergic contact dermatitis
L23.0	Allergic contact dermatitis due to metals
L23.1	Allergic contact dermatitis due to adhesives
L23.2	Allergic contact dermatitis due to cosmetics
L23.3	Allergic contact dermatitis due to drugs in contact with skin
L23.4	Allergic contact dermatitis due to dyes
L23.5	Allergic contact dermatitis due to other chemical products
L23.6	Allergic contact dermatitis due to food in contact with the skin
L23.7	Allergic contact dermatitis due to plants, except food
L23.8	Allergic contact dermatitis due to other agents
L23.81	Allergic contact dermatitis due to animal (cat) (dog) dander
L23.89	Allergic contact dermatitis due to other agents
L23.9	Allergic contact dermatitis, unspecified cause
Allergic rhinitis
J30.1	Allergic rhinitis due to pollen
J30.2	Other seasonal allergic rhinitis
J30.5	Allergic rhinitis due to food
J30.8	Other allergic rhinitis
J30.81	Allergic rhinitis due to animal (cat) (dog) hair and dander
J30.89	Other allergic rhinitis
J30.9	Allergic rhinitis, unspecified
Atopic dermatitis
L20	Atopic dermatitis
L20.0	Besnier's prurigo
L20.8	Other atopic dermatitis
L20.81	Atopic neurodermatitis
L20.82	Flexural eczema
L20.84	Intrinsic (allergic) eczema
L20.89	Other atopic dermatitis
L20.9	Atopic dermatitis, unspecified
Chronic non-allergic rhinitis
J31.0	Chronic rhinitis
Contact dermatitis
L23	Allergic contact dermatitis
L23.0	Allergic contact dermatitis due to metals
L23.1	Allergic contact dermatitis due to adhesives
L23.2	Allergic contact dermatitis due to cosmetics
L23.3	Allergic contact dermatitis due to drugs in contact with skin
L23.4	Allergic contact dermatitis due to dyes
L23.5	Allergic contact dermatitis due to other chemical products
L23.6	Allergic contact dermatitis due to food in contact with the skin
L23.7	Allergic contact dermatitis due to plants, except food
L23.8	Allergic contact dermatitis due to other agents
L23.81	Allergic contact dermatitis due to animal (cat) (dog) dander
L23.89	Allergic contact dermatitis due to other agents
L23.9	Allergic contact dermatitis, unspecified cause
L24	Irritant contact dermatitis
L24.0	Irritant contact dermatitis due to detergents
L24.1	Irritant contact dermatitis due to oils and greases
L24.2	Irritant contact dermatitis due to solvents
L24.3	Irritant contact dermatitis due to cosmetics
L24.4	Irritant contact dermatitis due to drugs in contact with skin
L24.5	Irritant contact dermatitis due to other chemical products
L24.6	Irritant contact dermatitis due to food in contact with skin
L24.7	Irritant contact dermatitis due to plants, except food
L24.8	Irritant contact dermatitis due to other agents
L24.81	Irritant contact dermatitis due to metals
L24.89	Irritant contact dermatitis due to other agents
L24.9	Irritant contact dermatitis, unspecified cause
L24.A0	Irritant contact dermatitis due to friction or contact with body fluids, unspecified
L24.A1	Irritant contact dermatitis due to saliva
L24.A2	Irritant contact dermatitis due to fecal, urinary or dual incontinence
L24.A9	Irritant contact dermatitis due friction or contact with other specified body fluids
L24.B	Irritant contact dermatitis related to stoma or fistula
L24.B0	Irritant contact dermatitis related to unspecified stoma or fistula
L24.B1	Irritant contact dermatitis related to digestive stoma or fistula
L24.B2	Irritant contact dermatitis related to respiratory stoma or fistula
L24.B3	Irritant contact dermatitis related to fecal or urinary stoma or fistula
L25	Unspecified contact dermatitis
L25.0	Unspecified contact dermatitis due to cosmetics
L25.1	Unspecified contact dermatitis due to drugs in contact with skin
L25.2	Unspecified contact dermatitis due to dyes
L25.3	Unspecified contact dermatitis due to other chemical products
L25.4	Unspecified contact dermatitis due to food in contact with skin
L25.5	Unspecified contact dermatitis due to plants, except food
L25.8	Unspecified contact dermatitis due to other agents
L25.9	Unspecified contact dermatitis, unspecified cause
Cutaneous t-cell lymphoma
C84.0	Mycosis fungoides
C84.A	Cutaneous t-cell lymphoma, unspecified
C84.A0	Cutaneous t-cell lymphoma, unspecified, unspecified site
C84.A1	Cutaneous t-cell lymphoma, unspecified lymph nodes of head, face, and neck
C84.A2	Cutaneous t-cell lymphoma, unspecified, intrathoracic lymph nodes
C84.A3	Cutaneous t-cell lymphoma, unspecified, intra-abdominal lymph nodes
C84.A4	Cutaneous t-cell lymphoma, unspecified, lymph nodes of axilla and upper limb
C84.A5	Cutaneous t-cell lymphoma, unspecified, lymph nodes of inguinal region and lower limb
C84.A6	Cutaneous t-cell lymphoma, unspecified, intrapelvic lymph nodes
C84.A7	Cutaneous t-cell lymphoma, unspecified, spleen
C84.A8	Cutaneous t-cell lymphoma, unspecified, lymph nodes of multiple sites
C84.A9	Cutaneous t-cell lymphoma, unspecified, extranodal and solid organ sites
Discoid lupus erythematosus
H01.12	Discoid lupus erythematosus of eyelid
H01.121	Discoid lupus erythematosus of right upper eyelid
H01.122	Discoid lupus erythematosus of right lower eyelid
H01.123	Discoid lupus erythematosus of right eye, unspecified eyelid
H01.124	Discoid lupus erythematosus of left upper eyelid
H01.125	Discoid lupus erythematosus of left lower eyelid
H01.126	Discoid lupus erythematosus of left eye, unspecified eyelid
H01.129	Discoid lupus erythematosus of unspecified eye, unspecified eyelid
L93.0	Discoid lupus erythematosus
Genital organ pruritus
L29.2	Pruritus vulvae
L29.3	Anogenital pruritus, unspecified
Granuloma annulare
L92.0	Granuloma annulare
Lichen simplex chronicus
L28.0	Lichen simplex chronicus
Maintenance therapy for asthma
J45	Asthma
J45.2	Mild intermittent asthma
J45.20	Mild intermittent asthma, uncomplicated
J45.3	Mild persistent asthma
J45.30	Mild persistent asthma, uncomplicated
J45.4	Moderate persistent asthma
J45.40	Moderate persistent asthma, uncomplicated
J45.5	Severe persistent asthma
J45.50	Severe persistent asthma, uncomplicated
J45.9	Other and unspecified asthma
J45.90	Unspecified asthma
J45.909	Unspecified asthma, uncomplicated
Plaque psoriasis
L40.0	Psoriasis vulgaris
L40.9	Psoriasis, unspecified
Pruritus ani
L29.0	Pruritus ani
L29.3	Anogenital pruritus, unspecified
Pruritus of skin
L29.8	Other pruritus
L29.81	Cholestatic pruritus
L29.89	Other pruritus
L29.9	Pruritus, unspecified
Pyoderma gangrenosum
L88	Pyoderma gangrenosum
Scalp psoriasis
L40.0	Psoriasis vulgaris
L40.1	Generalized pustular psoriasis
L40.4	Guttate psoriasis
L40.8	Other psoriasis
L40.9	Psoriasis, unspecified
Seborrheic dermatitis
L21	Seborrheic dermatitis
L21.0	Seborrhea capitis
L21.1	Seborrheic infantile dermatitis
L21.8	Other seborrheic dermatitis
L21.9	Seborrheic dermatitis, unspecified
Skin inflammation
L20	Atopic dermatitis
L20.8	Other atopic dermatitis
L20.89	Other atopic dermatitis
L20.9	Atopic dermatitis, unspecified
L21	Seborrheic dermatitis
L21.8	Other seborrheic dermatitis
L21.9	Seborrheic dermatitis, unspecified
L25	Unspecified contact dermatitis
L30.8	Other specified dermatitis
L30.9	Dermatitis, unspecified
L40	Psoriasis
L40.1	Generalized pustular psoriasis
L40.8	Other psoriasis
L40.9	Psoriasis, unspecified
R21	Rash and other nonspecific skin eruption