Flunisolide

Flunisolide belongs to the pharmacological class Corticosteroids. Flunisolide appears to have anti-inflammatory in the pulmonary system. Flunisolide carries out the anti-inflammatory actions through lipocortins, phospholipase A2 inhibitory protein, inhibiting the arachidonic acid, and also through the inhibition of or control of the biosynthesis of leukotrienes and prostaglandins.

Flunisolide had been approved for relieving symptoms and also for the treatment and maintenance of episodes of allergic rhinitis and asthma.

Flunisolide is completely and rapidly absorbed. Flunisolide is primarily metabolized by hepatic metabolism and is converted into S beta-OH metabolite. The urinary excretion following the nasal inhalation was found to be very low.

The common side effects associated with Flunisolide are nausea, cough, nosebleed, dry nose, sore throat, and hoarseness.

Flunisolide is available in the form of oral and nasal inhalation. Flunisolide is available in E.U., India, Australia, and Japan.

Flunisolide belongs to the pharmacological class of Corticosteroids. Flunisolide appears to have anti-inflammatory effects on the pulmonary system.

Flunisolide carries out the anti-inflammatory actions through lipocortins, phospholipase A2 inhibitory protein, inhibiting the arachidonic acid, and also through the inhibition of or control of the biosynthesis of leukotrienes and prostaglandins. Flunisolide had been approved for relieving symptoms and also for the treatment and maintenance of episodes of allergic rhinitis and asthma

The mean Tmax of Flunisolide was found to be about 0.09-0.17hours after oral inhalation of 320mcg dose and then mean Cmax was found to be 1.9 to 3.3 ng/mL

Flunisolide is available in Oral and Nasal Inhalation.

Flunisolide can be used in the treatment of:

• Asthma
• Allergic Rhinitis

Flunisolide might help to relieve symptoms and also for the maintenance and treatment of asthma and allergic rhinitis.

Flunisolide is approved for use in the following clinical indications:

• Allergic Rhinitis
• Asthma

Oral Inhalation

Aerosol or Metered Dose Inhalation.

1. The cap is removed from the MDI and chamber and Shaken well.

2. The MDI is inserted inside the open end of the chamber opposite to the mouthpiece.

3. The mouthpiece of the chamber is placed between your teeth and your lips are sealed tightly around it.

4. Now breathe out completely.

5. Then press the canister once.

6. Now breathe in slowly and completely through your mouth. If one hears a "horn-like" sound, then the person is breathing too quickly and needs to slow down.

7. Now hold your breath for 10 seconds and count to 10 slowly in order to allow the medication to reach the lungs.

8. The above steps is repeated for each puff ordered by the medical practitioners and wait about 1 minute in between puffs.

9. Lastly, replace the cap on your MDI when finished.

Nasal Inhalation

1. The top of the canister is pressed down four times or until a fine spray comes out in case one has not used this medicine for 7 days in a row, one must prime the spray, or if it is being used for the first time

2. After the nasal spray is primed, there will only be 120 doses or sprays.

3. The nose is gently blown before using the spray and head is tilted slightly backward and the tip of the nosepiece is inserted into one's nostril.

4. The opposite nostril is closed with a finger and one spray is released at the same time air is breathed in gently through the nostril.

5. Breath is held for a few seconds then air is breathed out slowly through the mouth.

6. The opposite nostril is sprayed using the same steps.

7. The nose should not be blown after using the spray.

Oral Inhalation: 80mcg, 160mcg,320mcg

Nasal Inhalation:0.025% per spray

Oral and Nasal Inhalation.

• Dosage Adjustments in Pediatric Patients:

Asthma: Lower dose of 80mcg in oral inhalation.

Smoking cessation and maintaining health are a must.

Caffeine should be avoided or limited to use as it might lead to the risk of nervousness, rapid heartbeat, nausea, palpitations,etc.

Alcohol should be avoided in the patient especially with an underlying liver disorder or liver dysfunction

Diet containing food with a added sugar, salt, preservatives,high glycemic index, saturated and trans fat food, red and processed meat, refined and high energy-dense foods, low fiber, low antioxidants, and vitamins needs to be restricted.

The dietary restrictions should be individualized as per the patient's requirements.

Flunisolide may be contraindicated under the following conditions:

• Hypersensitivity to the ingredients of the medication
• Asthma or previous conditions of asthmaticus

The treating physician should closely monitor the patients and keep pharmacovigilance as follows:

Local Infections

In clinical studies involving flunisolide, the localized infections with Candida albicans or Aspergillus niger have been found to be occurring in the pharynx and mouth and occasionally in the larynx. If oropharyngeal candidiasis develops, treatment with appropriate systemic or local antifungal therapy while still continuing with flunisolide, but at times therapy with flunisolide might need to be temporarily interrupted under close medical supervision.

Acute Asthma Episodes

Flunisolide is not a bronchodilator and has not been indicated for rapid relief of bronchospasm. It is advised to instruct patients to contact the physician immediately when episodes of asthma that do not respond to bronchodilators occur during the course of treatment using flunisolide. During such episodes, patients might require therapy with systemic corticosteroids.

Immunosuppression

Patients who use drugs that suppress the immune system are more prone to infections as compared to healthy individuals. Chickenpox and measles, for example, might lead to a more serious or even fatal course in non-immune children or adults on Flunisolide. In such children or adults who had no previous episodes of these diseases or been properly immunized, hence a particular care should be taken to avoid exposure.As there is a potential for worsening infections, Flunisolide should be exercised with action, if at all, in patients with untreated systemic fungal, bacterial, parasitic or viral infections; untreated active or quiescent tuberculosis infection of the respiratory tract; or ocular herpes simplex.

Transfer from Systemic Corticosteroids

Particular care should be taken in patients who are transferred from systemically active corticosteroids to flunisolide . It is because

of the fact that deaths due to adrenal insufficiency had occurred in asthmatic patients during and after transfer from systemic corticosteroids to less systemically available inhaled corticosteroids.

Reduction in Bone Mineral Density

Decrease in bone mineral density (BMD) has been observed with long-term administration of flunisolide. The clinical significance of small changes in bone mineral density with regard to long-term outcomes is unknown. It is advised to monitor patients with major risk factors for postmenopausal status, tobacco use, advanced age,chronic use of drugs that can reduce bone mass e.g., anticonvulsants and corticosteroids , etc and treat with established standards of care.

Effects on Growth

The orally inhaled corticosteroids, including flunisolide, might cause a reduction in growth velocity when it is administered to pediatric patients. Hence it is advised to monitor the growth of children and adolescents who are receiving flunisolide Inhalation Aerosol. To minimize the systemic effects of flunisolide, the lowest effective dose should be started for the treatment.

Glaucoma and Cataracts

Glaucoma, a condition which is said to cause an increased intraocular pressure, and cataracts , have been reported in patients who are on the long-term administration of flunisolide. It is advised to monitor patients closely, especially patients with a change in vision or with a history of glaucoma, or cataracts and increased intraocular pressure.

Paradoxical Bronchospasm

As along with other inhaled asthma medications, bronchospasm might occur with a sudden and immediate increase in wheezing after the dose . If bronchospasm occurs following dosing with flunisolide, it is advised to treat immediately with a fast-acting inhaled bronchodilator. It is also advised to discontinue treatment with flunisolide immediately and institute alternative therapy.

It is not known if flunisolide is secreted in human milk. As other corticosteroids are excreted in human milk, hence caution should be exercised when flunisolide Inhalation Aerosol is being administered to nursing women.

Teratogenic Effects

Pregnancy Category C.

There has been found to be well-controlled and adequate studies of flunisolide in pregnant women. Flunisolide Inhalation Aerosol is be used during pregnancy only if the potential benefits outweighs the risks associated with the fetus. As with other corticosteroids, flunisolide had been shown to be teratogenic and fetotoxic in animal studies i.e.in rabbits and rats at approximately one and three times the maximum recommended daily inhalation dose i.e. doses of 40 and 200 mcg/kg/day, respectively

Nonteratogenic Effects

Hypoadrenalism might occur in infants born to mothers who are receiving corticosteroids during pregnancy. It is advised that such infants should be carefully monitored.

No sufficient scientific evidence is traceable regarding the use and safety of Flunisolide in concurrent use with any particular food.

The adverse reactions related to Flunisolide can be categorized as:

• Common

N.A.

• Less common

Headache

Hoarseness

Nosebleed

Cough

Nausea

Vomiting

Stomach Cramps

Low Energy and Weakness

Runny Nose

Sore Throat

Crusting inside the Nose

A Lesion inside the Nose

Dizziness

Taste Impairment

Parosmia

• Rare

N.A.

The clinically relevant drug interactions of Flunisolide is briefly summarized here:

• Aldesleukin: Corticosteroids might diminish the antineoplastic activity of Aldesleukin.

• Cosyntropin: Corticosteroids (Orally Inhaled) might diminish the diagnostic activity of Cosyntropin.

• Desmopressin: Corticosteroids (Orally Inhaled) might enhance the hyponatremic activity of Desmopressin.

• Loxapine: Agents to Treat Airway Disease might improve the toxics effect of Loxapine.

• Tobacco (Smoked): Might diminish the therapeutic efficacy of Corticosteroids when orally Inhaled.

The common side effects of Flunisolide include the following:

• Sore throat
• Cough
• Nausea
• Hoarseness
• Sinusitis
• Aftertaste
• Nasal burning and stinging
• Nosebleed
• Dry nose

Pregnancy

Pregnancy Category C.

There has been found to be well-controlled and adequate studies of flunisolide in pregnant women. Flunisolide Inhalation Aerosol is be used during pregnancy only if the potential benefits outweighs the risks associated with the fetus. As with other corticosteroids, flunisolide had been shown to be teratogenic and fetotoxic in animal studies i.e.in rabbits and rats at approximately one and three times the maximum recommended daily inhalation dose on a mg/m2 basis, respectively i.e. doses of 40 and 200 mcg/kg/day, respectively

Nonteratogenic Effects

Hypoadrenalism might occur in infants born to mothers who are receiving corticosteroids during pregnancy. It is advised that such infants should be carefully monitored.

Nursing Mothers

It is not known if flunisolide is secreted in human milk. As other corticosteroids are excreted in human milk, flunisolide Inhalation Aerosol should be administered to nursing women with caution.

Pediatric Use

The safety and efficacy of flunisolide has been studied in children aged 4- 17 years. In clinical studies, the effectiveness of flunisolide Inhalation Aerosol was not established in children aged 4-5 years, although the adverse reaction profile observed in patients exposed to flunisolide was similar between the children aged 4-5 year (n=21), the children aged 6-11 year (n=210), the children aged 12-17 year (n=30), and those patients aged 18 years and older (n=258). The safety and efficacy of flunisolide has not been studied in patients aged less than 4 years.

Geriatric Use

Clinical studies of flunisolide Inhalation Aerosol had included 21 patients aged 65 to 78 who were to exposed to flunisolide Inhalation Aerosol. These studies didn't include sufficient numbers of patients who were aged 65 years and over to determine whether they respond differently from the younger patients.

Physician should be vigilant and knowledgeable about the treatment pertaining to the identification and treatment of overdosage of Flunisolide.

In a double-blind, placebo-controlled clinical study, 18 mg of flunisolide had been administered via the Chloroflurocrabon formulation over a 3-hour period i.e.nine times the maximum labeled daily dose in around 94 patients with acute asthma, and no clinically deleterious effects had been observed.

Pharmacodynamics

Flunisolide is said to be a synthetic corticosteroid. Flunisolide is administered either as an oral metered-dose inhaler in the treatment of asthma or as a nasal spray in the treatment of allergic rhinitis. Corticosteroids are found to be naturally occurring hormones that prevent or suppress inflammation and also immune responses. When given administered as intranasal spray, flunisolide reduces sneezing,watery nasal discharge (rhinorrhea), nasal congestion, postnasal drip, and itching throat the back of the throat that are common allergic symptoms.

Pharmacokinetics

• Absorption

Flunisolide is found to be rapidly absorbed, followed by oral inhalation. The mean values for Tmax, of flunisolide ranging from 0.09 to 0.17 hr followed by a single dose of 320 mcg flunisolide Inhalation Aerosol. The corresponding mean values for the Cmax, of flunisolide varies from 1.9 to 3.3 ng/mL. Oral bioavailability is found to be less than 7%.

• Distribution

Flunisolide is found to be extensively distributed inside the body, with mean values for apparent volume of distribution ranging between 170 to 350 L after a single dose of 320 mcg flunisolide Inhalation Aerosol.

• Metabolism

Flunisolide is found to be extensively converted to 6ß-OH flunisolide and to water-soluble conjugates when going through the first pass in the liver. Conversion to 6ß-OH flunisolide, which is the only circulating metabolite is detected in man, is found to occur via the cytochrome P450 enzyme system, which is particularly the enzyme CYP3A4. 6ß-OH flunisolide has found to be a low corticosteroid potency which is about ten times less potent than cortisol and around more than 200 times less potent than flunisolide. Maximum levels of 6ß-OH flunisolide were found to be 0.66 mcg/mL after a single dose of 320 mcg flunisolide Inhalation Aerosol, and 0.71 mcg/mL following multiple doses of flunisolide Inhalation Aerosol.

• Elimination

Urinary excretion of flunisolide is found to be low which is less than 1% of the administered dose of flunisolide is found to be recovered in urine followed by inhalation. The half-life values for 6ß-OH flunisolide ranges from 3.1 to 5.1 hrs after Inhalation administration of flunisolide ,the Aerosol in the dose-ranging of 160 mcg to 320 mcg

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