Fluticasone

Dosage for Fluticasone must be individualized based on the condition being treated and the patient's response to therapy.

• Allergic Rhinitis (Nasal Spray): The standard starting dose for adults is 200 mcg daily, administered as two sprays (50 mcg per spray) in each nostril once daily. Alternatively, some patients may prefer one spray in each nostril twice daily (morning and evening). Once symptoms are controlled, your doctor may suggest reducing the dose to one spray in each nostril daily (100 mcg total) for maintenance.
• Asthma (Inhalation): Dosage varies significantly based on previous asthma therapy. For patients previously on bronchodilators alone, the starting dose is often 88 mcg twice daily. For those switching from other inhaled steroids, doses may range from 88 mcg to 440 mcg twice daily. The maximum recommended dose is 880 mcg twice daily.
• Topical Use: Apply a thin film of cream or ointment to the affected area once or twice daily. Do not use for more than 4 consecutive weeks without medical reassessment.

• Allergic Rhinitis: For children aged 4 to 11 years, the typical dose is one spray (50 mcg) in each nostril once daily. The maximum dose is two sprays in each nostril daily. Use should be limited to the shortest duration necessary.
• Asthma: For children aged 4 to 11 years, the usual dose is 50 mcg to 100 mcg twice daily. Fluticasone is generally not recommended for asthma maintenance in children under 4 years of age unless specifically directed by a specialist.

Renal Impairment

No dosage adjustment is typically required for patients with renal (kidney) impairment, as the drug is primarily cleared via the liver and feces.

Hepatic Impairment

Since Fluticasone is metabolized by the liver, patients with significant hepatic (liver) impairment (e.g., cirrhosis) should be monitored closely. Increased systemic exposure may occur, potentially leading to side effects like adrenal suppression. Your doctor may use the lowest effective dose.

Elderly Patients

Clinical studies have not identified significant differences in safety or effectiveness between elderly patients and younger adults. However, because older adults are more likely to have decreased hepatic or cardiac function, healthcare providers usually start at the lower end of the dosing range.

• Nasal Spray: Shake the bottle gently before use. Prime the pump if it hasn't been used for 7 days or more by spraying into the air until a fine mist appears. Blow your nose before use. Close one nostril, insert the tip into the other, and spray while breathing in gently. Avoid spraying directly onto the nasal septum (the wall between the nostrils).
• Inhaler (MDI): Shake well for 5 seconds. Exhale fully, place the mouthpiece in your mouth, and press the canister while inhaling deeply. Hold your breath for 10 seconds. Crucial: Always rinse your mouth with water and spit it out after using an inhaled steroid to prevent oral candidiasis (thrush).
• Storage: Store at room temperature (68°F to 77°F). Keep the inhaler away from open flames and do not puncture the canister.

If you miss a dose, take it as soon as you remember. However, if it is almost time for your next scheduled dose, skip the missed dose and resume your regular schedule. Do not double the dose to catch up.

Acute overdose is unlikely to be life-threatening due to low systemic absorption. However, chronic overdosage (using too much over a long period) can lead to hypercorticism (excess cortisol) and adrenal suppression. Symptoms may include thinning skin, easy bruising, and changes in body fat distribution. If an overdose is suspected, contact a poison control center or seek emergency medical care immediately.

> Important: Follow your healthcare provider's dosing instructions. Do not adjust your dose or stop the medication without medical guidance, as sudden discontinuation of high doses can lead to withdrawal symptoms.

Most side effects of Fluticasone are localized to the site of administration and are generally mild. Common reactions include:

• Epistaxis (Nosebleeds): This is the most frequently reported side effect for the nasal spray. It usually manifests as minor spotting or bloody mucus.
• Headache: Many patients report mild to moderate headaches, particularly when starting therapy.
• Pharyngitis and Nasopharyngeal Irritation: A 'scratchy' or sore throat and general irritation in the back of the nose and throat.
• Cough and Hoarseness: Inhaled Fluticasone can cause a temporary change in voice (dysphonia) or a persistent dry cough.

• Nasal Burning or Stinging: A transient sensation immediately after using the nasal spray.
• Nausea and Vomiting: Occasionally reported with systemic absorption or post-nasal drip of the medication.
• Dizziness: Some patients may feel lightheaded shortly after administration.
• Upper Respiratory Tract Infection: Increased susceptibility to minor viral colds or sinus infections.

• Nasal Septal Perforation: In rare cases, long-term use of nasal steroids can lead to a small hole in the wall between the nostrils. This is often preceded by crusting and severe dryness.
• Glaucoma and Cataracts: Increased intraocular pressure has been documented with long-term, high-dose use of both inhaled and nasal corticosteroids.
• Growth Retardation: While rare at standard doses, prolonged use in children may slightly slow the rate of growth. Healthcare providers monitor height regularly in pediatric patients.

> Warning: Stop taking Fluticasone and call your doctor immediately if you experience any of these serious reactions:

• Anaphylaxis or Severe Allergic Reactions: Symptoms include hives, swelling of the face, lips, or tongue, and difficulty breathing or swallowing.
• Candida Albicans (Oral Thrush): White patches in the mouth or throat, which indicate a fungal infection. This is a risk if the mouth is not rinsed after inhalation.
• Adrenal Suppression: Signs include extreme fatigue, muscle weakness, weight loss, and low blood pressure. This occurs when the body stops producing its own cortisol.
• Immunosuppression: Increased vulnerability to severe infections. If you are exposed to chickenpox or measles while on Fluticasone, contact your doctor immediately.
• Vision Changes: Blurred vision, eye pain, or seeing 'halos' around lights.

Prolonged use of Fluticasone, especially at higher-than-recommended doses, can lead to systemic steroid effects. These include a reduction in bone mineral density (increasing the risk of osteoporosis), thinning of the skin (atrophy), and easy bruising. In rare cases, patients may develop 'Cushingoid' features, such as a rounded face (moon face) and a fatty hump between the shoulders. Regular monitoring by a healthcare provider is essential for anyone using Fluticasone for more than several months.

No FDA black box warnings currently exist for Fluticasone propionate as a monotherapy. However, combination products containing Fluticasone and long-acting beta-agonists (LABAs) previously carried warnings regarding asthma-related death risks; however, the FDA removed these specific warnings in 2017 following large-scale safety trials that demonstrated no significant increase in serious asthma-related events when LABAs are used in combination with an inhaled corticosteroid like Fluticasone.

Report any unusual symptoms to your healthcare provider. You may also report side effects to the FDA at 1-800-FDA-1088.

Fluticasone is a powerful medication that requires careful management. It is not a 'rescue' medication and will not stop an acute asthma attack. Patients must have a separate fast-acting inhaler (like albuterol) for emergencies. Consistent daily use is required for the medication to be effective in preventing symptoms.

No FDA black box warnings for Fluticasone propionate when used as a single-ingredient product.

• Allergic Reactions: Patients with a known hypersensitivity to Fluticasone or any of the inactive ingredients (such as milk proteins in some dry powder inhalers) must not use this drug. Anaphylaxis, though rare, has been reported.
• Infections: Corticosteroids can mask signs of infection and further suppress the immune system. Fluticasone should be used with extreme caution in patients with active or quiescent tuberculosis, untreated fungal, bacterial, or systemic viral infections, or ocular herpes simplex.
• Adrenal Suppression and HPA Axis: When switching from systemic steroids (like oral prednisone) to Fluticasone, there is a risk of adrenal insufficiency. The body may not produce enough natural cortisol to handle stress (e.g., surgery or severe infection). This transition must be managed carefully by a physician.
• Ocular Risks: Long-term use of Fluticasone may increase the risk of developing cataracts or glaucoma. Patients with a history of these conditions or those who notice vision changes should undergo regular eye examinations.
• Wound Healing: Because corticosteroids inhibit the inflammatory response necessary for healing, Fluticasone nasal spray should not be used in patients with recent nasal septal ulcers, nasal surgery, or nasal trauma until healing has occurred.

Healthcare providers may require the following monitoring for patients on long-term Fluticasone therapy:

• Growth Monitoring: For pediatric patients, height should be tracked at every visit to ensure the drug is not impacting growth velocity.
• Bone Density: For patients at high risk for osteoporosis, periodic bone mineral density (BMD) scans may be recommended.
• Ocular Exams: Annual or bi-annual eye exams to check for increased intraocular pressure.
• HPA Axis Testing: In rare cases where high doses are used, a cosyntropin stimulation test may be performed to check adrenal function.

Fluticasone generally does not cause sedation or cognitive impairment. It is considered safe to drive or operate machinery while using this medication, provided you do not experience rare side effects like severe dizziness or blurred vision.

There are no known direct interactions between Fluticasone and alcohol. However, alcohol can sometimes trigger asthma or allergy symptoms in certain individuals, so moderation is advised.

Do not stop using Fluticasone abruptly, especially if you have been using it at high doses. While 'withdrawal' is less common than with oral steroids, a sudden stop can lead to a return of severe inflammatory symptoms. Your doctor will provide a tapering schedule if you need to stop the medication.

> Important: Discuss all your medical conditions, especially any history of tuberculosis, eye problems, or recent infections, with your healthcare provider before starting Fluticasone.

While Fluticasone has low systemic absorption, certain drugs can block its metabolism, leading to dangerously high levels of the steroid in the blood.

• Ritonavir (Norvir): This protease inhibitor used for HIV is a potent inhibitor of the CYP3A4 enzyme. Co-administration with Fluticasone is generally contraindicated because it can lead to systemic corticosteroid effects, including Cushing's syndrome and adrenal suppression.

• Strong CYP3A4 Inhibitors: Drugs such as Ketoconazole, Itraconazole, Clarithromycin, and Nefazodone can significantly increase the concentration of Fluticasone in the body. If these must be used together, your doctor will monitor you closely for signs of steroid toxicity.
• Other Corticosteroids: Taking Fluticasone alongside oral prednisone or other topical/inhaled steroids increases the cumulative dose of steroids, raising the risk of HPA axis suppression and side effects like bone loss.

• Desmopressin: Corticosteroids can increase the water-retaining effect of desmopressin, potentially leading to low sodium levels (hyponatremia).
• Diuretics (Water Pills): Some diuretics can cause potassium loss; when combined with high doses of steroids, the risk of hypokalemia (low potassium) may increase, though this is rare with localized Fluticasone.

• Grapefruit Juice: Grapefruit is a known inhibitor of the CYP3A4 enzyme in the gut and liver. While the impact on inhaled Fluticasone is likely minimal, consuming large amounts of grapefruit juice could theoretically increase the systemic absorption of the drug.
• Dairy: Some dry powder inhalers (DPIs) contain lactose. While the amount is tiny, patients with severe milk protein allergies (not just lactose intolerance) should avoid these specific formulations and use MDIs instead.

• St. John's Wort: This herbal supplement is an inducer of CYP3A4. It may speed up the metabolism of Fluticasone, potentially reducing its effectiveness in controlling asthma or allergies.
• Echinacea: Some believe Echinacea may interfere with the immunosuppressive effects of corticosteroids, though clinical evidence for this interaction with Fluticasone is limited.

Fluticasone generally does not interfere with standard blood or urine tests. However, because it can suppress the HPA axis, it may interfere with tests designed to measure adrenal function, such as the ACTH stimulation test or urinary free cortisol tests.

Management Strategy

To manage these interactions, healthcare providers typically:

1. 1Review all current medications before prescribing Fluticasone.
2. 2Use the lowest effective dose of Fluticasone if a CYP3A4 inhibitor is necessary.
3. 3Monitor for 'red flag' symptoms like rapid weight gain, facial swelling, or extreme fatigue.

> Important: Tell your doctor about ALL medications, supplements, and herbal products you are taking, including over-the-counter allergy or cold medicines.

Fluticasone must NEVER be used in the following circumstances:

• Hypersensitivity: If you have had a documented severe allergic reaction (anaphylaxis, angioedema) to Fluticasone propionate or any component of the formulation (e.g., lactose in certain inhalers), you must avoid this drug. The mechanism is an IgE-mediated immune response that can be life-threatening.
• Status Asthmaticus: Fluticasone is contraindicated as the primary treatment for status asthmaticus or other acute episodes of asthma where intensive measures are required. It does not act quickly enough to reverse bronchospasm.
• Untreated Localized Infection: For the nasal spray, use is contraindicated in the presence of untreated localized infection involving the nasal mucosa (e.g., a severe fungal or bacterial infection in the nose).

In these cases, the benefits of Fluticasone must be carefully weighed against the risks:

• Active Tuberculosis (TB): Because steroids suppress the immune response, they can allow TB to worsen or reactivate.
• Ocular Herpes Simplex: There is a risk of corneal perforation if steroids are used during an active infection.
• Recent Nasal Surgery or Trauma: Until the nose has fully healed, the use of nasal steroids can delay wound healing and increase the risk of septal perforation.
• Severe Hepatic Impairment: Patients with liver failure may accumulate higher levels of the drug, requiring very close monitoring for systemic side effects.

Patients who are allergic to other corticosteroids (such as budesonide, triamcinolone, or mometasone) may occasionally experience cross-sensitivity with Fluticasone. If you have had a skin rash or breathing difficulty with any other steroid, inform your doctor before starting Fluticasone.

> Important: Your healthcare provider will evaluate your complete medical history, including any past infections or surgeries, before prescribing Fluticasone.

Fluticasone is classified as Pregnancy Category C (under the older FDA system). This means that while animal studies have shown some adverse effects on the fetus (such as cleft palate at very high doses), there are no adequate, well-controlled studies in pregnant women.

• Risk-Benefit Analysis: Uncontrolled asthma during pregnancy poses a significant risk to both the mother and the fetus (including hypoxia and pre-eclampsia). Therefore, most experts agree that maintaining asthma control with Fluticasone is generally safer than leaving asthma untreated.
• Trimester Considerations: Use during the first trimester is usually approached with caution, though systemic absorption is very low.

It is not known whether Fluticasone is excreted in human breast milk. However, because systemic levels after inhalation or nasal use are extremely low, the amount of drug a nursing infant would be exposed to is likely negligible. Healthcare providers generally consider Fluticasone compatible with breastfeeding, but monitoring the infant for signs of growth suppression is a prudent precaution.

Fluticasone is approved for use in children as young as 4 years old for both asthma and allergic rhinitis.

• Growth Effects: A primary concern in pediatrics is the potential for corticosteroids to slow growth. Clinical trials have shown that children using inhaled Fluticasone may experience a small reduction in growth velocity (approximately 1 cm per year). This effect is usually most pronounced in the first year of treatment and may not affect final adult height.
• Dosing: Pediatric patients should always use the lowest effective dose to minimize these risks.

In older adults, Fluticasone is generally safe and effective. However, the following concerns apply:

• Bone Health: Elderly patients are at higher risk for osteoporosis. Since long-term steroids can reduce bone density, calcium and Vitamin D supplementation may be recommended.
• Thinning Skin: Older patients using topical Fluticasone may experience skin tearing or bruising more easily.
• Polypharmacy: Older adults are more likely to be on multiple medications (like CYP3A4 inhibitors for heart disease), increasing the risk of drug interactions.

No dosage adjustments are needed for patients with kidney disease. The drug is not significantly cleared by the kidneys, and dialysis does not affect its concentration.

Since Fluticasone is metabolized by the liver, patients with Child-Pugh Class B or C hepatic impairment should be monitored for signs of hypercorticism (excessive steroid levels). The drug's half-life may be prolonged in these patients.

> Important: Special populations require individualized medical assessment to ensure the safest possible treatment plan.

Fluticasone is a potent agonist of the human glucocorticoid receptor. Its anti-inflammatory action is mediated through several pathways:

1. 1Gene Regulation: It binds to cytosolic receptors, which then translocate to the nucleus and bind to Glucocorticoid Response Elements (GRE). This inhibits the transcription of inflammatory genes (like NF-kappa-B).
2. 2Cellular Inhibition: It reduces the number and activity of inflammatory cells, including mast cells, eosinophils, T-lymphocytes, and macrophages.
3. 3Vasoconstriction: It induces the contraction of small blood vessels in the nasal mucosa, which directly reduces swelling and congestion.

Fluticasone has a high affinity for the glucocorticoid receptor—approximately 18 times greater than dexamethasone. The onset of action for the nasal spray is typically 12 hours, with peak effects seen after several days. For asthma, improvement in lung function may be seen within 24 hours, but maximum benefit usually requires 1 to 2 weeks of continuous therapy.

| Parameter | Value |

|---|---|

| Bioavailability | <2% (Nasal), 10-20% (Inhalation) |

| Protein Binding | 99% |

| Half-life | 7.8 to 10 hours |

| Tmax | 0.5 to 1 hour (Inhalation) |

| Metabolism | Hepatic (CYP3A4) |

| Excretion | Fecal (>95%), Renal (<5%) |

• Molecular Formula: C25H27F3O4S
• Molecular Weight: 500.5 g/mol
• Solubility: Practically insoluble in water; freely soluble in dimethyl sulfoxide (DMSO).
• Structure: A trifluorinated corticosteroid with a propionate ester group at the 17-alpha position, which enhances its lipophilicity and receptor binding.

Fluticasone is classified as a synthetic corticosteroid and a glucocorticoid receptor agonist. It is part of the 'Inhaled Corticosteroid' (ICS) class for respiratory health and 'Topical Corticosteroid' (Group II or III) for dermatology.